A 3.2 V Binary Layered Oxide Cathode for Potassium-Ion Batteries.

Potassium-ion batteries (KIBs) can offer high energy density, cyclability, and operational safety while being economical due to the natural abundance of potassium. Utilizing graphite as an anode, suitable cathodes can realize full cells. Searching for potential cathodes, this work introduces P3-type K0.5Ni1/3Mn2/3O2 layered oxide as a potential candidate synthesized by a simple solid-state method. The material works as a 3.2 V cathode combining Ni redox at high voltage and Mn redox at low voltage and exhibits highly reversible K+ ion (de)insertion at ambient and elevated (40-50 °C) temperatures. First-principles calculations suggest the ground state in-plane Mn-Ni ordering in the MO2 sheets is strongly correlated to the K-content in the framework, leading to an interwoven and alternative row ordering of Ni-Mn in K0.5Ni1/3Mn2/3O2. Postmortem and electrochemical titration reveal the occurrence of a solid solution mechanism during K+ (de)insertion. The findings suggest that the Ni addition can effectively tune the electronic and structural properties of the cathode, leading to improved electrochemical performance. This work provides new insights in the quest to develop potential low-cost Co-free KIB cathodes for practical applications in stationary energy storage.

Giant electrostriction-like response from defective non-ferroelectric epitaxial BaTiO3 integrated on Si (100).

Lead-free, silicon compatible materials showing large electromechanical responses comparable to, or better than conventional relaxor ferroelectrics, are desirable for various nanoelectromechanical devices and applications. Defect-engineered electrostriction has recently been gaining popularity to obtain enhanced electromechanical responses at sub 100 Hz frequencies. Here, we report record values of electrostrictive strain coefficients (M31) at frequencies as large as 5 kHz (1.04×10-14 m2/V2 at 1 kHz, and 3.87×10-15 m2/V2 at 5 kHz) using A-site and oxygen-deficient barium titanate thin-films, epitaxially integrated onto Si. The effect is robust and retained upon cycling upto 6 million times. Our perovskite films are non-ferroelectric, exhibit a different symmetry compared to stoichiometric BaTiO3 and are characterized by twin boundaries and nano polar-like regions. We show that the dielectric relaxation arising from the defect-induced features correlates well with the observed giant electrostriction-like response. These films show large coefficient of thermal expansion (2.36 × 10-5/K), which along with the giant M31 implies a considerable increase in the lattice anharmonicity induced by the defects. Our work provides a crucial step forward towards formulating guidelines to engineer large electromechanical responses even at higher frequencies in lead-free thin films.

Modulation-doping a correlated electron insulator.

Correlated electron materials (CEMs) host a rich variety of condensed matter phases. Vanadium dioxide (VO2) is a prototypical CEM with a temperature-dependent metal-to-insulator (MIT) transition with a concomitant crystal symmetry change. External control of MIT in VO2-especially without inducing structural changes-has been a long-standing challenge. In this work, we design and synthesize modulation-doped VO2-based thin film heterostructures that closely emulate a textbook example of filling control in a correlated electron insulator. Using a combination of charge transport, hard X-ray photoelectron spectroscopy, and structural characterization, we show that the insulating state can be doped to achieve carrier densities greater than 5 × 1021 cm-3 without inducing any measurable structural changes. We find that the MIT temperature (TMIT) continuously decreases with increasing carrier concentration. Remarkably, the insulating state is robust even at doping concentrations as high as ~0.2 e-/vanadium. Finally, our work reveals modulation-doping as a viable method for electronic control of phase transitions in correlated electron oxides with the potential for use in future devices based on electric-field controlled phase transitions.

Formulation strategies for the development of high drug-loaded amorphous solid dispersions.

Amorphous solid dispersions (ASD) have gained tremendous attention over the past two decades as one of the most promising techniques for enhancing the solubility of poorly water-soluble drugs. However, low drug loading is one of the major challenges of ASD technology that limits its commercialization to only a few drug candidates. Increasing the drug loading increases the risk of recrystallization during storage (solid state) and/or during dissolution (solution state). Various formulation and process-related strategies have been explored that open the possibility of formulating high drug-loaded ASDs without the risk of recrystallization. Here, we review various formulation approaches, such as the use of surfactants, mesoporous silicas, polymer combinations, in situ thermal crosslinking, structural modification of polymeric carriers, and surface nanocoating using minerals. We also discuss the mechanisms by which these approaches inhibit solid state and/or solution state recrystallization.

Tunable encapsulation of sessile droplets with solid and liquid shells.

Droplet encapsulations using liquid or solid shells are of significant interest in microreactors, drug delivery, crystallization, and cell growth applications. Despite progress in droplet-related technologies, tuning micron-scale shell thickness over a large range of droplet sizes is still a major challenge. In this work, we report capillary force assisted cloaking using hydrophobic colloidal particles and liquid-infused surfaces. The technique produces uniform solid and liquid shell encapsulations over a broad range (5-200 µm shell thickness for droplet volume spanning over four orders of magnitude). Tunable liquid encapsulation is shown to reduce the evaporation rate of droplets by up to 200 times with a wide tunability in lifetime (1.5 h to 12 days). Further, we propose using the technique for single crystals and cell/spheroid culture platforms. Stimuli-responsive solid shells show hermetic encapsulation with tunable strength and dissolution time. Moreover, scalability, and versatility of the technique is demonstrated for on-chip applications.

Realizing avalanche criticality in neuromorphic networks on a 2D hBN platform.

Networks and systems which exhibit brain-like behavior can analyze information from intrinsically noisy and unstructured data with very low power consumption. Such characteristics arise due to the critical nature and complex interconnectivity of the brain and its neuronal network. We demonstrate a system comprising of multilayer hexagonal boron nitride (hBN) films contacted with silver (Ag), which can uniquely host two different self-assembled networks, which are self-organized at criticality (SOC). This system shows bipolar resistive switching between the high resistance state (HRS) and the low resistance state (LRS). In the HRS, Ag clusters (nodes) intercalate in the van der Waals gaps of hBN forming a network of tunnel junctions, whereas the LRS contains a network of Ag filaments. The temporal avalanche dynamics in both these states exhibit power-law scaling, long-range temporal correlation, and SOC. These networks can be tuned from one to another with voltage as a control parameter. For the first time, two different neural networks are realized in a single CMOS compatible, 2D material platform.

An Aqueous Route to Oxygen-Deficient Wake-Up-Free La-Doped HfO2 Ferroelectrics for Negative Capacitance Field Effect Transistors.

The crucial role of nanocrystalline morphology in stabilizing the ferroelectric orthorhombic (o)-phase in doped-hafnia films is achieved via chemical solution deposition (CSD) by intentionally retaining carbonaceous impurities to inhibit grain growth. However, in the present study, large-grained (>100 nm) La-doped HfO2 (HLO) films are grown directly on silicon by adopting engineered water-diluted precursors with a minimum carbonaceous load and excellent shelf life. The o-phase stabilization is accomplished through a well-distributed La dopant, which generates uniformly populated oxygen vacancies, eliminating the need for oxygen-scavenging electrodes. These oxygen-deficient HLOs show a maximum remnant polarization of 37.6 µC/cm2 (2Pr) without wake-up and withstand large fields (>6.2 MV/cm). Furthermore, CSD-HLO in series with Al2O3 improves switching of MOSFETs (with an amorphous oxide channel) based on the negative capacitance effect. Thus, uniformly distributed oxygen vacancies serve as a standalone factor in stabilizing the o-phase, enabling efficient wake-up-free ferroelectricity without the need for nanostructuring, capping stresses, or oxygen-reactive electrodes.

Emergence of field-induced memory effect in spin ices.

Out-of-equilibrium investigation of strongly correlated materials deciphers the hidden equilibrium properties. Herein, we have investigated the out-of-equilibrium magnetic properties of polycrystalline Dy2Ti2O7and Ho2Ti2O7spin ices. Our experimental findings reveal the emergence of magnetic field-induced anomalous hysteresis observed solely in temperature-and magnetic field-dependent AC susceptibility measurements. The observed memory effect (anomalous thermomagnetic hysteresis) exhibits a strong dependence on both thermal and non-thermal driving variables. Owing to the non-collinear spin structure, the applied DC bias magnetic field produces quenched disorder sites in the cooperative Ising spin matrix and suppresses the spin-phonon coupling. These quench disorders create a dynamic spin correlation, having slow spin relaxation and quick decay time, which additionally contribute to AC susceptibility. The initial conditions and measurement protocol decide the magnitude and sign of this dynamical term contributing to AC susceptibility. It is being suggested that such out-of-equilibrium properties arise from the combined influences of geometric frustration, disorder, and the cooperative nature of spin dynamics exhibited by these materials.

Lessons from hafnium dioxide-based ferroelectrics.

A bit more than a decade after the first report of ferroelectric switching in hafnium dioxide-based ultrathin layers, this family of materials continues to elicit interest. There is ample consensus that the observed switching does not obey the same mechanisms present in most other ferroelectrics, but its exact nature is still under debate. Next to this fundamental relevance, a large research effort is dedicated to optimizing the use of this extraordinary material, which already shows direct integrability in current semiconductor chips and potential for scalability to the smallest node architectures, in smaller and more reliable devices. Here we present a perspective on how, despite our incomplete understanding and remaining device endurance issues, the lessons learned from hafnium dioxide-based ferroelectrics offer interesting avenues beyond ferroelectric random-access memories and field-effect transistors. We hope that research along these other directions will stimulate discoveries that, in turn, will mitigate some of the current issues. Extending the scope of available systems will eventually enable the way to low-power electronics, self-powered devices and energy-efficient information processing.

A Comprehensive Review of mRNA Vaccines.

mRNA vaccines have been demonstrated as a powerful alternative to traditional conventional vaccines because of their high potency, safety and efficacy, capacity for rapid clinical development, and potential for rapid, low-cost manufacturing. These vaccines have progressed from being a mere curiosity to emerging as COVID-19 pandemic vaccine front-runners. The advancements in the field of nanotechnology for developing delivery vehicles for mRNA vaccines are highly significant. In this review we have summarized each and every aspect of the mRNA vaccine. The article describes the mRNA structure, its pharmacological function of immunity induction, lipid nanoparticles (LNPs), and the upstream, downstream, and formulation process of mRNA vaccine manufacturing. Additionally, mRNA vaccines in clinical trials are also described. A deep dive into the future perspectives of mRNA vaccines, such as its freeze-drying, delivery systems, and LNPs targeting antigen-presenting cells and dendritic cells, are also summarized.

Recent Advances in Amorphous Solid Dispersions: Preformulation, Formulation Strategies, Technological Advancements and Characterization.

Amorphous solid dispersions (ASDs) are among the most popular and widely studied solubility enhancement techniques. Since their inception in the early 1960s, the formulation development of ASDs has undergone tremendous progress. For instance, the method of preparing ASDs evolved from solvent-based approaches to solvent-free methods such as hot melt extrusion and Kinetisol®. The formulation approaches have advanced from employing a single polymeric carrier to multiple carriers with plasticizers to improve the stability and performance of ASDs. Major excipient manufacturers recognized the potential of ASDs and began introducing specialty excipients ideal for formulating ASDs. In addition to traditional techniques such as differential scanning calorimeter (DSC) and X-ray crystallography, recent innovations such as nano-tomography, transmission electron microscopy (TEM), atomic force microscopy (AFM), and X-ray microscopy support a better understanding of the microstructure of ASDs. The purpose of this review is to highlight the recent advancements in the field of ASDs with respect to formulation approaches, methods of preparation, and advanced characterization techniques.

TEM based applications in solid state nanopores: From fabrication to liquid in-situ bio-imaging.

Nanopore-based techniques are widely used owing to their diverse applications such as DNA sequencing, ion detection, gas filtration, protein sequencing, and numerous other applications. Although commercialized sequencing methods are based on biological nanopores, solid-state nanopore technology is emerging due to its several advantages over biological nanopores, such as its tunable size, chemical and mechanical stability, and possibilities for easy integration with measurement electronics. The unavailability of rapid, low-cost, easy solid-state nanopore fabrication methods with industrial scalability is one of the current bottlenecks in this domain. Among all nanopore fabrication techniques, the Transmission electron microscope (TEM) based fabrication method is frequently used in research labs due to its capability of drilling and tuning nanopores with high accuracy. Given that there are no other methods capable of imaging and fabricating nanopores simultaneously, it is important to discuss the related methods and protocols of TEM. This review focuses on the various aspects of nanopore technology using TEM, from pore fabrication to imaging. Hybrid nanopores are also emerging, which combine the benefits of biological and solid-state nanopores. These can be formed by integrating DNA origami with solid-state nanopores. Creating and imaging DNA origami structures also presents several challenges. We also review DNA origami imaging using conventional TEM. We hope that this review will provide a one-stop reference to TEM applications on solid-state nanopores from fabrication to bioimaging and boost further research in this area.

Aversion liquid-filled drug releasing capsule (3D-RECAL): A novel technology for the development of immediate release abuse deterrent formulations using a fused deposition modelling (FDM) 3D printer.

COVID19 has caused a significant socioeconomic burden worldwide. Opioid crisis was further intensified with the increasing number of opioid overdose/misuse related deaths in last two years. Abusers have adopted newer/efficient methods for manipulating and abusing commercial opioid formulations. Food and Drug Administration (FDA) has been strategizing tirelessly to prevent misuse/abuse of prescription opioids. One of the strategies is to develop an abuse deterrent formulation (ADF). The current study aims to develop a novel 3D printed drug-releasing capsule shell filled with an aversion liquid (3D-RECAL). Primarily, metformin hydrochloride (MT, model drug) loaded printable filaments of polyvinyl alcohol was prepared using hot melt extrusion. Following extrusion, a 3D printed capsule shell was designed and fabricated using a single nozzle fuse deposition modelling 3D printer. An aversion liquid to be filled in 3D-RECAL capsules was prepared by combining sudan black and sodium polyacrylamide starch in oil base. Mechanical analysis of extruded filaments suggested that the filaments with 20%w/w MT had a higher mechanical strength compared to other drug loadings. Instantaneous gelling and large black non-snortable particles were formed during solvent extraction and physical manipulation studies, respectively. Due to the drug being embedded in the capsule shell, MT release was immediately started with >85% of MT release within 45 mins in 0.1 N HCl. Due to the everlasting need for the newer efficient ADF technologies, 3D-RECAL can be a step in the right direction towards saving lives, providing safe and effective measures to deterring abusers.

Reversible oxygen migration and phase transitions in hafnia-based ferroelectric devices.

Unconventional ferroelectricity exhibited by hafnia-based thin films-robust at nanoscale sizes-presents tremendous opportunities in nanoelectronics. However, the exact nature of polarization switching remains controversial. We investigated a La0.67Sr0.33MnO3/Hf0.5Zr0.5O2 capacitor interfaced with various top electrodes while performing in situ electrical biasing using atomic-resolution microscopy with direct oxygen imaging as well as with synchrotron nanobeam diffraction. When the top electrode is oxygen reactive, we observe reversible oxygen vacancy migration with electrodes as the source and sink of oxygen and the dielectric layer acting as a fast conduit at millisecond time scales. With nonreactive top electrodes and at longer time scales (seconds), the dielectric layer also acts as an oxygen source and sink. Our results show that ferroelectricity in hafnia-based thin films is unmistakably intertwined with oxygen voltammetry.

Process optimization of twin-screw melt granulation of fenofibrate using design of experiment (DoE).

The purpose of this study was to optimize the melt granulation process of fenofibrate using twin-screw granulator. Initial screening was performed to select the excipients required for melt granulation process. A 3 × 3 factorial design was used to optimize the processing conditions using the % drug loading (X1) and screw speed (X2) as the independent parameters and granule friability (Y1) % yield (Y2) as the dependent parameters. The effect of the independent parameters on the dependent parameters was determined using response surface plots and contour plots. A linear relationship was observed between % drug loading (X1) and % friability (Y1) and a quadratic relationship was observed between the independent parameters (X1 and X2) and % yield (Y2). The processing conditions for optimum granules were determined using numerical and graphical optimization and it was found that 15% drug loading at 50 rpm results in maximum % yield of 82.38% and minimum friability of 7.88%. The solid-state characterization of the optimized granules showed that the drug turned from crystalline state to amorphous state during melt granulation process. The optimized granules were compressed into tablets using Purolite® as the super disintegrating agent. The optimized formulation showed >85% drug release in 0.75% SLS solution within 60 min.

Overdose and Alcohol Sensitive Immediate Release System (OASIS) for Deterring Accidental Overdose or Abuse of Drugs.

Death from an accidental or intentional overdose of sleeping tablets has increased exponentially in the USA. Furthermore, the simultaneous consumption of sleeping tablets with alcoholic beverages not only intensifies the effect of sleeping tablets but also leads to blackouts, sleepwalking, and death in many cases. In this article, we proposed a unique and innovative technology to prevent multi-tablet and alcohol-associated abuse of sleeping tablet. Agonist- and antagonist-loaded polymeric filaments of appropriate Eudragit® polymers were prepared using hot melt extrusion. Metoprolol tartrate and hydrochlorothiazide were used as model drugs in place of zolpidem tartrate (agonist-BCS class I) and flumazenil (antagonist-BCS class IV), respectively. Crushed filaments were converted into a tablet with a novel rapidly soluble co-processed alkalizing agent. Dissolution studies of single tablet and multiple tablets (5) in fasted state simulated gastric fluid (FaSSGF) confirmed that the release of the agonist was significantly (p < 0.0001) reduced in multi-tablet dissolution. Furthermore, the release of antagonist was significantly higher when tablet was exposed to FaSSGF+20% ethanol and various alcoholic beverages. Thus, appropriate use of Eudragit® polymer's chemistry could help design a tablet to prevent the release of agonist in case of overdose and simultaneous release of antagonist when consumed with alcohol.

Abuse deterrent immediate release film technology (ADRIFT): A novel bilayer film technology for limiting intentional drug abuse.

Prescription opioid abuse also known as opioid epidemic has been an ever-growing problem in the United States. It has been associated with numerous emergencies and mortality with significant burden on healthcare system. Amongst various approaches proposed by FDA, development of an abuse deterrent formulation is one of the key strategies to address this opioid crisis. Existing abuse deterrent technologies have several deficiencies which enable abusers to manipulate/bypass it. The proposed study aims to develop and optimize an abuse-deterrent immediate release bilayer film (ADRIFT). A novel material with distinct process engineering was employed to achieve immediate drug release with nasal/intravenous abuse deterrent properties. Drug layer (DL) composed of a rapidly soluble film forming polymer - polyvinyl alcohol (PVA) while various solvent system and biocompatible polymers were screened to incorporate sodium polyacrylamide starch (KPX) in abuse deterrent layer (AL). Mechanical analysis of ADRIFT suggested that individual excipients played significant role in improving the mechanical strength of ADRIFT. Spontaneous formation of highly viscous gels in different solvents and resistance to mill into fine powder support the injection and snorting abuse deterrent potential, respectively. Immediate release (>85% release) was achieved in < 30mins, indicating that there was no interference between either of the layers towards their specific purposes. Hence, our novel yet simple ADRIFT oral film technology could potentially be useful in manufacturing immediate release abuse-deterrent formulation of opioid drugs.

Multi-dose oral abuse deterrent formulation of loperamide using hot melt extrusion.

Loperamide, an over the counter anti-diarrheal drug, also infamously referred to as "poor man's methadone". Due to the ease of availability and low price, people/patients abuse it by consuming more than 30 tablets to achieve euphoric effect and to combat opioid withdrawal. But supratherapeutic doses of loperamide result in severe respiratory depression, cardiac dysrhythmia and mortality. To address this issue, we developed a unique and innovative technology to deter multi-dose oral abuse. The concept is to design a tablet which can immediate release loperamide in diarrheic patients (single tablet) while stops loperamide release in case of intentional multi-dose ingestion. Loperamide was molecularly dispersed into gastric soluble cationic polymers - Eudragit® EPO and Kollicoat® Smartseal 100P using hot melt extrusion to obtain filament. Filaments were milled and compressed into tablets ((Eudragit® EPO (SJU1) and Kollicoat® Smartseal (SJU2)) with optimized amount of L-Arginine. Dissolution in 250 mL of Fasted state simulated gastric fluid (FaSSGF) revealed that single tablet of Imodium® (marketed formulation) and SJU1 showed >85% of release within 15 min. Most importantly, in multi-unit dissolution (15 tablets), Imodium® exhibited >90% release but SJU tablets showed <2% of drug release thus demonstrating its ability to deter multi-dose oral abuse.

Abuse Deterrent Immediate Release Egg-Shaped Tablet (Egglets) Using 3D Printing Technology: Quality by Design to Optimize Drug Release and Extraction.

Opioid abuse is a growing problem and has become a national health crisis over the past decade in the USA. Oral ingestion, snorting, and injection are the most commonly employed routes of abuse for an immediate release product. To circumvent these issues, we have developed an egg-shaped tablet (egglet) using fused deposition modeling (FDM) 3D printing technology. Drug-loaded polymeric filaments (1.5 mm) were prepared using hot melt extrusion (HME) followed by printing into egglets of different sizes and infill densities. Based on printability and crush resistance, polyvinyl alcohol (PVA) was found to be the most suitable polymer for the preparation of abuse deterrent egglets. Further, egglets were evaluated and optimized for mechanical manipulation using household equipment, milling, particle size distribution, solvent extraction, and drug release as per the FDA guidance (November 2017). A multifactorial design was used to optimize egglets for solvent extraction and drug release. Extreme hardness (> 500 N) and very large particle size (> 1 mm) on mechanical manipulation confirmed the snorting deterring property while less than 15% drug extraction in 5 min (% Sext) demonstrated the deterrence for injection abuse. Quality target product profile D85 < 30 min and % Sext < 15 was achieved with egglets of 6 mm diameter, 45% infill density, and 15% w/w drug loading. Dose of drug can be easily customized by varying dimension and infill density without altering the composition. HME coupled with FDM 3D printing could be a promising tool in the preparation of patient-tailored, immediate release abuse deterrent formulation.