Measurement of Electric Charge in a Charged Hydroxyapatite Dielectric Using Pendant Drop.

A simple noninvasive measurement method which allows one to determine the trapped charge in a biocompatible hydroxyapatite dielectric is developed. The hydroxyapatite samples are charged by electron beam with energy 30 keV and total irradiated charge ranging from 2 × 10-9 C to 2 × 10-7 C. The value of the trapped charge is determined by analyzing the shape change of a liquid droplet hanging from a needle in proximity of the charged sample surface. The shape change of the pendant drop in the field of gravity is commonly utilized in the measurements of the surface free tension (SFT) of liquids. The external electric field leads to a further modification of the droplet shape and to an effective change of the SFT. The change of the SFT as a function of distance between the droplet and sample and the critical distance at which the droplet detaches from the needle are measured for various values of the irradiated charge. These two quantities are also derived theoretically by considering the trapped charge as a single fitting parameter. We can thus determine the trapped charge in two independent noninvasive ways. It is noteworthy that our method is easily implementable into the standard pendant drop setups. As a practical application of the method, a long-term charge stability of the charged hydroxyapatite is demonstrated, thus paving the way toward quantitative studies of its bioactivity in dependence on the value of the trapped charge.

Circular Polarization Conversion in Single Plasmonic Spherical Particles.

Temporal and spectral behaviors of plasmons determine their ability to enhance the characteristics of metamaterials tailored to a wide range of applications, including electric-field enhancement, hot-electron injection, sensing, as well as polarization and angular momentum manipulation. We report a dark-field (DF) polarimetry experiment on single particles with incident circularly polarized light in which gold nanoparticles scatter with opposite handedness at visible wavelengths. Remarkably, for silvered nanoporous silica microparticles, the handedness conversion occurs at longer visible wavelengths, only after adsorption of molecules on the silver. Finite element analysis (FEA) allows matching the circular polarization (CP) conversion to dominant quadrupolar contributions, determined by the specimen size and complex susceptibility. We hypothesize that the damping accompanying the adsorption of molecules on the nanostructured silver facilitates the CP conversion. These results offer new perspectives in molecule sensing and materials tunability for light polarization conversion and control of light spin angular momentum at submicroscopic scale.

Guest Molecule-Mediated Energy Harvesting in a Conformationally Sensitive Peptide-Metal Organic Framework.

The apparent piezoelectricity of biological materials is not yet fully understood at the molecular level. In particular, dynamic noncovalent interactions, such as host-guest binding, are not included in the classical piezoelectric model, which limits the rational design of eco-friendly piezoelectric supramolecular materials. Here, inspired by the conformation-dependent mechanoresponse of the Piezo channel proteins, we show that guest-host interactions can amplify the electromechanical response of a conformationally mobile peptide metal-organic framework (MOF) based on the endogenous carnosine dipeptide, demonstrating a new type of adaptive piezoelectric supramolecular material. Density functional theory (DFT) predictions validated by piezoresponse force microscopy (PFM) measurements show that directional alignment of the guest molecules in the host carnosine-zinc peptide MOF channel determines the macroscopic electromechanical properties. We produce stable, robust 1.4 V open-circuit voltage under applied force of 25 N with a frequency of 0.1 Hz. Our findings demonstrate that the regulation of host-guest interactions could serve as an efficient method for engineering sustainable peptide-based power generators.

Pathway Complexity in Supramolecular Porphyrin Self-Assembly at an Immiscible Liquid-Liquid Interface.

Nanostructures that are inaccessible through spontaneous thermodynamic processes may be formed by supramolecular self-assembly under kinetic control. In the past decade, the dynamics of pathway complexity in self-assembly have been elucidated through kinetic models based on aggregate growth by sequential monomer association and dissociation. Immiscible liquid-liquid interfaces are an attractive platform to develop well-ordered self-assembled nanostructures, unattainable in bulk solution, due to the templating interaction of the interface with adsorbed molecules. Here, we report time-resolved in situ UV-vis spectroscopic observations of the self-assembly of zinc(II) meso-tetrakis(4-carboxyphenyl)porphyrin (ZnTPPc) at an immiscible aqueous-organic interface. We show that the kinetically favored metastable J-type nanostructures form quickly, but then transform into stable thermodynamically favored H-type nanostructures. Numerical modeling revealed two parallel and competing cooperative pathways leading to the different porphyrin nanostructures. These insights demonstrate that pathway complexity is not unique to self-assembly processes in bulk solution and is equally valid for interfacial self-assembly. Subsequently, the interfacial electrostatic environment was tuned using a kosmotropic anion (citrate) in order to influence the pathway selection. At high concentrations, interfacial nanostructure formation was forced completely down the kinetically favored pathway, and only J-type nanostructures were obtained. Furthermore, we found by atomic force microscopy and scanning electron microscopy that the J- and H-type nanostructures obtained at low and high citric acid concentrations, respectively, are morphologically distinct, which illustrates the pathway-dependent material properties.

Control of piezoelectricity in amino acids by supramolecular packing.

Piezoelectricity, the linear relationship between stress and induced electrical charge, has attracted recent interest due to its manifestation in biological molecules such as synthetic polypeptides or amino acid crystals, including gamma (γ) glycine. It has also been demonstrated in bone, collagen, elastin and the synthetic bone mineral hydroxyapatite. Piezoelectric coefficients exhibited by these biological materials are generally low, typically in the range of 0.1-10 pm V-1, limiting technological applications. Guided by quantum mechanical calculations we have measured a high shear piezoelectricity (178 pm V-1) in the amino acid crystal beta (ß) glycine, which is of similar magnitude to barium titanate or lead zirconate titanate. Our calculations show that the high piezoelectric coefficients originate from an efficient packing of the molecules along certain crystallographic planes and directions. The highest predicted piezoelectric voltage constant for ß-glycine crystals is 8 V mN-1, which is an order of magnitude larger than the voltage generated by any currently used ceramic or polymer.

Racemic Amino Acid Piezoelectric Transducer.

Single crystal L-amino acids can exhibit technologically useful piezoelectric and nonlinear optical properties. Here we predict, using density functional theory, the piezoelectric charge and strain and voltage tensors of the racemic amino acid DL alanine, and use the modeling data to guide the first macroscopic and nanoscopic piezoelectric measurements on DL-alanine single crystals and polycrystalline aggregates. We demonstrate voltage generation of up to 0.8 V from DL-alanine crystal films under simple manual compression, twice as high as other amino acid crystals. Our results suggest that net molecular chirality is not a prerequisite for piezoelectric behavior in organic crystals. The transducer presented herein demonstrates that DL-alanine crystals can be used in applications such as temperature and force measurement in biosensors, data storage in flexible electronic devices, and mechanical actuation in energy harvesters.

Thermal effects of mobile phones on human auricle region.

Mobile phones have become an indispensable utility to modern society, with international use increasing dramatically each year. The GSM signal operates at 900 MHz, 1800 MHz and 2250 MHz, may potentially cause harm to human tissue. Yet there is no in silico model to aid design these devices to protect from causing potential thermal effect. Here we present a model of sources of heating in a mobile phone device with experimental verification during the phone call. We have developed this mobile phone thermal model using first principles on COMSOL® Multiphysics modelling platform to simulate heating effect in human auricle region due to mobile phone use. In particular, our model considered both radiative and non-radiative heating from components such as the lithium ion battery, CPU circuitry and the antenna. The model showed the distribution and effect of the heating effect due to mobile phone use and considered impact of battery discharge rate, battery capacity, battery cathode material, biological tissue distance, antenna radio-wave frequency and intensity. Furthermore, the lithium ion battery heating was validated during experiments using temperature sensors with an excellent agreement between simulated and experimental data (<1% variation). Mobile phone heating during a typical call has also been simulated and compared with experimental infrared thermographic imaging. Importantly, we found that 1800 MHz frequency of data transmission showed the highest temperature increase in the fat/water phantom used in this simulation. We also successfully compared heating distribution in human auricle region during mobile phone use with clinical thermographic images with reasonable qualitative and quantitative agreements. In summary, our model provides a foundation to conceive thermal and other physical effects caused by mobile phone use and allow for the understanding of potential negative health effects thus supporting and promoting personalized and preventive medicine using thermography.

Spatial-domain filter enhanced subtraction microscopy and application to mid-IR imaging.

We have experimentally investigated the enhancement in spatial resolution by image subtraction in mid-infrared central solid-immersion lens (c-SIL) microscopy. The subtraction exploits a first image measured with the c-SIL point-spread function (PSF) realized with a Gaussian beam and a second image measured with the beam optically patterned by a silicon π-step phase plate, to realize a centrally hollow PSF. The intense sides lobes in both PSFs that are intrinsic to the SIL make the conventional weighted subtraction methods inadequate. A spatial-domain filter with a kernel optimized to match both experimental PSFs in their periphery was thus developed to modify the first image prior to subtraction, and this resulted in greatly improved performance, with polystyrene beads 1.4 ± 0.1 µm apart optically resolved with a mid-IR wavelength of 3.4 µm in water. Spatial-domain filtering is applicable to other PSF pairs, and simulations show that it also outperforms conventional subtraction methods for the Gaussian and doughnut beams widely used in visible and near-IR microscopy.

Doubling the far-field resolution in mid-infrared microscopy.

The spatial resolution in far-field mid-infrared (λ>2.5 µm) microscopy and micro-spectroscopy remains limited with the full-width at half maximum of the point-spread function ca. λ/1.3; a value that is very poor in comparison to that commonly accessible with visible and near-infrared optics. Hereafter, it is demonstrated however that polymer beads that are centre-to-centre spaced by λ/2.6 can be resolved in the mid-infrared. The more than 2-fold improvement in resolution in the far-field is achieved by exploiting a newly constructed scanning microscope built around a mid-infrared optical parametric oscillator and a central solid-immersion lens, and by enforcing the linear polarization unidirectional resolution enhancement with a novel and robust specimen error minimization based on a particle swarm optimization. The method is demonstrated with specimens immersed in air and in water, and its robustness shown by the analysis of dense and complex self-assembled bead islands.

Mapping electron-beam-injected trapped charge with scattering scanning near-field optical microscopy.

Scattering scanning near-field optical microscopy (s-SNOM) has been demonstrated as a valuable tool for mapping the optical and optoelectronic properties of materials with nanoscale resolution. Here we report experimental evidence that trapped electric charges injected by an electron beam at the surface of dielectric samples affect the sample-dipole interaction, which has direct impact on the s-SNOM image content. Nanoscale mapping of the surface trapped charge holds significant potential for the precise tailoring of the electrostatic properties of dielectric and semiconductive samples, such as hydroxyapatite, which has particular importance with respect to biomedical applications. The methodology developed here is highly relevant to semiconductor device fabrication as well.

Superparamagnetic iron oxide nanocargoes for combined cancer thermotherapy and MRI applications.

Nanoparticle-based cancer diagnosis-therapy integrative systems (cancer theranostics) represent an emerging approach in oncology. To address this issue in the present work iron oxide (γ-Fe2O3-maghemite) nanoparticles (IONPs) were encapsulated within the matrix of (bis(p-sulfonatophenyl)phenylphosphine)-methoxypolyethylene glycol-thiol (mPEG) polymer vesicles using a two-step process for active chemotherapeutic cargo loading in cancer theranostics. This formation method gives simple access to highly reactive surface groups present on IONPs together with good control over the vesicle size (50-100 nm). The simultaneous loading of a chemotherapeutic drug cargo (doxorubicin) and its in vitro release in cancer cells was achieved. The feasibility of controlled drug release under different pH conditions was demonstrated in the case of encapsulated doxorubicin molecules, showing the viability of the concept of stimulated drug delivery for magneto-chemotherapy. These polymer-magnetic nanocargoes (PMNCs) exhibit enhanced contrast properties that open potential applications for magnetic resonance imaging. These self-assembled magnetic polymersomes can be used as efficient multifunctional nanocarriers for combined therapy and imaging.

Effects of Polydopamine Functionalization on Boron Nitride Nanotube Dispersion and Cytocompatibility.

Boron nitride nanotubes (BNNTs) have unique physical properties, of value in biomedical applications; however, their dispersion and functionalization represent a critical challenge in their successful employment as biomaterials. In the present study, we report a process for the efficient disentanglement of BNNTs via a dual surfactant/polydopamine (PD) process. High-resolution transmission electron microscopy (HR-TEM) indicated that individual BNNTs become coated with a uniform PD nanocoating, which significantly enhanced dispersion of BNNTs in aqueous solutions. Furthermore, the cytocompatibility of PD-coated BNNTs was assessed in vitro with cultured human osteoblasts (HOBs) at concentrations of 1, 10, and 30 µg/mL and over three time-points (24, 48, and 72 h). In this study it was demonstrated that PD-functionalized BNNTs become individually localized within the cytoplasm by endosomal escape and that concentrations of up to 30 µg/mL of PD-BNNTs were cytocompatible in HOBs cells following 72 h of exposure.

Nanosystems: the use of nanoalloys, metallic, bimetallic, and magnetic nanoparticles in biomedical applications.

There is a growing interest in the use of nanosystems such as nanoalloys, bimetallic nanoparticles, metallic nanoparticles and magnetic nanoparticles in biomedical applications. These applications can be as diverse as hyperthermic treatments; targeted drug delivery; bio-imaging; cell labelling and gene delivery. The use of nanoalloys in these applications has received only limited attention due to the fact that there were many unanswered questions and concerns regarding nanoparticles and nanoalloys such as their stability over time, tendency to agglomerate, chemical activity, ease of oxidation, biocompatibility and cytotoxicity. In this chapter we survey current applications and advances in magnetic nanoparticles used in these biomedical applications so as to understand the materials properties that can pave the way for the use of nanoalloys as a potential alternative or improve solutions that are offered by current materials.

Label free detection of specific protein binding using a microwave sensor.

The specific binding of streptavidin to biotinylated protein A was demonstrated using a microwave detection system. In control experiments, the degree of non-specific binding was negligible. The method of detection was used to monitor the adsorption of two other proteins, cytochrome c and glucose oxidase, on to the IDE microwave sensor surface. The response of the sensor was also examined on different substrate materials, with detection of protein binding observed obtained on both smooth, conductive (gold) and on rough, insulating (hydroxyapatite) surfaces.

Surface charge and carbon contamination on an electron-beam-irradiated hydroxyapatite thin film investigated by photoluminescence and phase imaging in atomic force microscopy.

The surface properties of hydroxyapatite, including electric charge, can influence the biological response, tissue compatibility, and adhesion of biological cells and biomolecules. Results reported here help in understanding this influence by creating charged domains on hydroxyapatite thin films deposited on silicon using electron beam irradiation and investigating their shape, properties, and carbon contamination for different doses of incident injected charge by two methods. Photoluminescence laser scanning microscopy was used to image electrostatic charge trapped at pre-existing and irradiation-induced defects within these domains, while phase imaging in atomic force microscopy was used to image the carbon contamination. Scanning Auger electron spectroscopy and Kelvin probe force microscopy were used as a reference for the atomic force microscopy phase contrast and photoluminescence laser scanning microscopy measurements. Our experiment shows that by combining the two imaging techniques the effects of trapped charge and carbon contamination can be separated. Such separation yields new possibilities for advancing the current understanding of how surface charge influences mediation of cellular and protein interactions in biomaterials.

Modification of Living Diatom, Thalassiosira weissflogii, with a Calcium Precursor through a Calcium Uptake Mechanism: A Next Generation Biomaterial for Advanced Delivery Systems.

The diatom's frustule, characterized by its rugged and porous exterior, exhibits a remarkable biomimetic morphology attributable to its highly ordered pores, extensive surface area, and unique architecture. Despite these advantages, the toxicity and nonbiodegradable nature of silica-based organisms pose a significant challenge when attempting to utilize these organisms as nanotopographically functionalized microparticles in the realm of biomedicine. In this study, we addressed this limitation by modulating the chemical composition of diatom microparticles by modulating the active silica metabolic uptake mechanism while maintaining their intricate three-dimensional architecture through calcium incorporation into living diatoms. Here, the diatom Thalassiosira weissflogii was chemically modified to replace its silica composition with a biodegradable calcium template, while simultaneously preserving the unique three-dimensional (3D) frustule structure with hierarchical patterns of pores and nanoscale architectural features, which was evident by the deposition of calcium as calcium carbonate. Calcium hydroxide is incorporated into the exoskeleton through the active mechanism of calcium uptake via a carbon-concentrating mechanism, without altering the microstructure. Our findings suggest that calcium-modified diatoms hold potential as a nature-inspired delivery system for immunotherapy through antibody-specific binding.

High resolution imaging with differential infrared absorption micro-spectroscopy.

Although confocal infrared (IR) absorption micro-spectroscopy is well established for far-field chemical imaging, its scope remains restricted since diffraction limits the spatial resolution to values a little above half the radiation wavelength. Yet, the successful implementations of below-the-diffraction limit far-field fluorescence microscopies using saturated irradiation patterns for example for stimulated-emission depletion and saturated structured-illumination suggest the possibility of using a similar optical patterning strategy for infrared absorption mapping at high resolution. Simulations are used to show that the simple mapping of the difference in transmitted/reflected IR energy between a saturated vortex-shaped beam and a Gaussian reference with a confocal microscope affords the generation of high-resolution vibrational absorption images. On the basis of experimentally relevant parameters, the simulations of the differential absorption scheme reveal a spatial resolution better than a tenth of the wavelength for incident energies about a decade above the saturation threshold. The saturated structured illumination concepts are thus expected to be compatible with the establishment of point-like point-spread functions for measuring the absorbance of samples with a scanning confocal microscope recording the differential transmission/reflection.

Raman Spectroscopy: A Tool for Molecular Fingerprinting of Brain Cancer.

Brain cancer is one of those few cancers with very high mortality and low five-year survival rate. First and foremost reason for the woes is the difficulty in diagnosing and monitoring the progression of brain tumors both benign and malignant, noninvasively and in real time. This raises a need in this hour for a tool to diagnose the tumors in the earliest possible time frame. On the other hand, Raman spectroscopy which is well-known for its ability to precisely represent the molecular markers available in any sample given, including biological ones, with great sensitivity and specificity. This has led to a number of studies where Raman spectroscopy has been used in brain tumors in various ways. This review article highlights the fundamentals of Raman spectroscopy and its types including conventional Raman, SERS, SORS, SRS, CARS, etc. are used in brain tumors for diagnostics, monitoring, and even theragnostics, collating all the major works in the area. Also, the review explores how Raman spectroscopy can be even more effectively used in theragnostics and the clinical level which would make them a one-stop solution for all brain cancer needs in the future.

Functionalized manganese iron oxide nanoparticles: a dual potential magneto-chemotherapeutic cargo in a 3D breast cancer model.

Localized heat generation from manganese iron oxide nanoparticles (MIONPs) conjugated with chemotherapeutics under the exposure of an alternating magnetic field (magneto-chemotherapy) can revolutionize targeted breast cancer therapy. On the other hand, the lack of precise control of local temperature and adequate MIONP distribution in laboratory settings using the conventional two-dimensional (2D) cellular models has limited its further translation in tumor sites. Our current study explored advanced 3D in vitro tumor models as a promising alternative to replicate the complete range of tumor characteristics. Specifically, we have focused on investigating the effectiveness of MIONP-based magneto-chemotherapy (MCT) as an anticancer treatment in a 3D breast cancer model. To achieve this, chitosan-coated MIONPs (CS-MIONPs) are synthesized and functionalized with an anticancer drug (doxorubicin) and a tumor-targeting aptamer (AS1411). CS-MIONPs with a crystallite size of 16.88 nm and a specific absorption rate (SAR) of 181.48 W g-1 are reported. In vitro assessment of MCF-7 breast cancer cell lines in 2D and 3D cell cultures demonstrated anticancer activity. In the 2D and 3D cancer models, the MIONP-mediated MCT reduced cancer cell viability to about 71.48% and 92.2%, respectively. On the other hand, MIONP-mediated MCT under an AC magnetic field diminished spheroids' viability to 83.76 ± 2%, being the most promising therapeutic modality against breast cancer.

Quantitative surface free energy with micro-colloid probe pairs.

Measurement of the surface free energy (SFE) of a material allows the prediction of its adhesion properties. Materials can have microscale or sub-microscale surface inhomogeneities, engineered or random, which affect the surface macroscopic behaviour. However, quantitative characterization of the SFE at such length scales remains challenging in view of the variety of instruments and techniques available, the poor knowledge of critical variables and parameters during measurements and the need for appropriate contact models to derive the SFE from the measurements. Failure to characterize adhesion correctly may result in defective components or lengthy process optimization costing billions to industry. Conversely, for planar and homogeneous surfaces, contact angle (CA) measurements are standardized and allow for calculating the SFE using for example the Owen-Wendt model, relying only on the properties of the probing liquids. As such, we assessed and report here a method to correlate quantitative measurements of force-distance curves made with an atomic force microscope (AFM) and with silica and polystyrene (PS) colloidal probe pairs, with quantitative CA measurements and CA-derived SFE values. We measured five surfaces (mica, highly oriented pyrolytic graphite, thermally grown silica on silicon, silicon, and silicon with a super-hydrophobic coating), ranging from hydrophilic to super-hydrophobic, and found an excellent classification of the AFM measurements when these are represented by a set of principal components (PCs), and when both silica and PS colloidal probes are considered together. A regression of the PCs onto the CA measurements allows recovery of the SFE at the length scale of the colloidal probes, which is here ca. 1 micron. We found that once the PC-regression model is built, test sets of only ten AFM force-distance curves are sufficient to predict the local SFE with the calibrated silica and PS colloidal probes.