Application of stealth nanobeacon for traceability assurance in pharmaceutical tablets via surface-enhanced Raman scattering during the tablet coating process.

Microtaggant technologies for on-dose authentication have garnered significant interest for use in the anti-counterfeit activities and traceability of pharmaceutical dosage forms. Previously, we proposed a stealth nanobeacon (NB) comprising self-assembled colloidal gold nanoparticles with reporter molecules that demonstrated characteristic surface-enhanced Raman scattering (SERS) activity. However, the integration of such microtaggants into standard production lines remains underexplored. In this study, we demonstrate the incorporation of NB into tablet coatings using a simple mixing method with conventional coating solutions. Rapid and discernible SERS responses from the NB-coated tablets were observed in response to laser excitation at 785 nm for 0.1s, implying that it is an advanced and efficient method for counterfeit detection. In addition, the SERS intensity of NB increased with coating time, suggesting that NB can be used as a tracer for the real-time monitoring of coating thickness. Furthermore, NB-coated tablets were indistinguishable from NB-free tablets, even during colorimetric analysis. These results suggest that the NB possesses stealth properties and can be easily incorporated into counterfeit detection products.

Gold Nanoparticles Enhance the Tumor Growth-Suppressing Effects of Cetuximab and Radiotherapy in Head and Neck Cancer In Vitro and In Vivo.

INTRODUCTION: Head and neck squamous cell carcinoma (HNSCC) treatment includes surgery, radiotherapy, and immunotherapy with the aim of eradicating cancer cells without affecting normal tissues. HNSCC expresses epidermal growth factor receptor (EGFR) and cetuximab, an IgG1 monoclonal antibody targeting epidermal growth factor receptor, has been approved for the treatment of HNSCC. However, cetuximab has low reactivity and induces serious side effects. Gold nanoparticles (AuNPs) were reported to enhance the local antitumor effects of radiotherapy without damaging normal cells. METHODS AND RESULTS: This study investigated the in vitro effects of single and combination therapy with AuNPs (1.0 nM), cetuximab (30 nM), and radiotherapy (4 Gy) on a human HNSCC cell line, HSC-3. Combination treatment of AuNPs + cetuximab + radiotherapy markedly reduced HSC-3 numbers and proliferation and enhanced apoptosis compared with single and double combination treatments. Furthermore, the in vivo combination treatment (AuNPs + cetuximab + radiotherapy) of a xenograft model of HSC-3 cells transplanted into nude mice (BALB/cAJcl-nu/nu) reduced the tumor volume compared with the controls. Scanning electron microscopy demonstrated the presence of AuNPs in tumor tissues and toxicity analysis indicated that AuNPs had no toxic effect on normal tissues. CONCLUSIONS: This study showed that AuNPs alone do not have a tumor-suppressing effect, but they sensitize tumors to radiotherapy and bind to cetuximab, leading to enhanced antitumor effects.

APELLA: Open-Source, miniaturized All-in-One powered Lab-on-a-Disc platform.

We present an unconventional approach to a common Lab-on-a-Disc (LoD) that combines a quadcopter propulsion system, a miniaturized 2.4 GHz Wi-Fi spy camera, 9.74 Watt Qi wireless power, and an Arduino into an open-source, miniaturized All-in-one powered lab-on-disc platform (APELLA). The quadcopter propulsion generates thrust to rotate (from 0.1 to 24.5 Hz) or shake the LoD device, while the spy camera enables a real-time (30 frames per second) and high definition (1280 × 720 pixels) visualization of microfluidic channels without requiring a bulky and heavy stroboscopic imaging setup. A mobile device can communicate with an Arduino microcontroller inside the APELLA through a Bluetooth interface for closed loop and sequential frequency control. In a proof-of-concept study, the APELLA achieved comparable mixing efficiency to a traditional spin stand and can capture rapid microfluidic events at low rotational frequencies (<5Hz). The APELLA is low-cost (c.a. 100 Euro), compact (15.6 × 15.6 × 10 cm3), lightweight (0.59 kg), portable (powered by a 5 V USB power bank), and energy efficient (uses < 6% power of the conventional system), making it ideal for field deployment, education, resource-limited labs.

In situ synchrotron X-ray scission of polytetrafluoroethylene chains and elucidation of dry etching.

We investigated the mechanism of polytetrafluoroethylene (PTFE) chain scission through in situ hard X-ray photoelectron spectroscopy at room temperature, 200 °C, and 230 °C. The C-C bonds in the main chain and C-F bonds in the side chains were broken, and F desorption from the PTFE surface was observed at room temperature. The formation of CF3 was also observed from the recombination of broken C-C bonds in the main chain and detached F, which were not induced by soft X-rays. In contrast, when the PTFE substrate was irradiated with hard X-rays at 200 °C, the CF3 intensity initially produced by recombination reactions decreased with irradiation time, and the photoelectron spectrum retained the original PTFE spectrum. Under these conditions, the F1s/C1s intensity ratio did not change with the irradiation time; hence, the fragment containing only CF2, the chemical composition of the original PTFE, was desorbed. When the substrate temperature was 230 °C, the CF3 intensity increased in relation to that at 200 °C. This result indicated that the formation of CF3 via recombination reactions of broken molecular chains is enhanced by thermal assistance. These phenomena were considered to be based on the balance between recombination and desorption by photochemical and pyrochemical reactions. These results will lead to a better understanding of the use of X-ray-irradiated fluorine resins and PTFE in potential space-based environments. This study will also promote the improvement of PTFE microfabrication methods and thin-film formation using synchrotron radiation.

[Microtaggant Technology for Ensuring Traceability of Pharmaceutical Formulations: Potential for Anti-counterfeiting Measures, Distribution and Medication Management].

The globalization of drug trade has led to the increased production of falsified medicines. In addition, poor medication adherence increases the costs of healthcare. The need to manage medication has given rise to marketing of highly functional networked digital medicine. Therefore, a growing need has emerged to ensure the traceability of pharmaceutical products from shipment to patient distribution. Microtaggant technologies that can encode individual numbers on pharmaceutical products are expected to serve achieving this goal. Taggants are a class of materials that can be applied to an object to make it identifiable, like barcodes and holograms. Since the smaller size of microtaggant make it invisible to naked eyes, it is more difficult to reverse-engineer than conventional taggants. The U.S. Food and Drug Administration (FDA) has established guidelines for the use of microtaggants. Many studies have explored the use of various analytical technologies and materials as the microtaggants. However, the advantages and disadvantages of each method have not been established yet. In this review, recent research on the use of microtaggants for anti-counterfeiting is summarized and compared to current anti-counterfeiting technologies with spectrographic methods, distribution management systems with barcodes, and medication management systems with sensor devices. We also discuss the microtaggants implementation costs and security level.

Physical stability of stealth nanobeacon using surface-enhanced Raman scattering for anti-counterfeiting and monitoring medication adherence: Deposition on various coating tablets.

Microtaggant technologies can encode individual numbers on coating tablet to authenticate pharmaceutical products and, therefore, combat the global spread of falsified medicine. In this study, a novel microtaggant, stealth nanobeacon (NB), with surface-enhanced Raman scattering (SERS) activity was applied to various coating tablets and its physical stability was evaluated. The NBs were composed of a reporter molecule (AH, adenine hydrochloride) and prepared with different sizes of gold nanoparticles (AuNPs). The NBs were directly deposited on the surface of various model coatings (e.g., hydroxypropyl cellulose, hydroxypropyl methyl cellulose, Eudragit® RS30D, ethyl cellulose). To investigate physical stability of the NB on the coating tablets, SERS spectra of the NB after friability test and acceleration test (store at 75% RH, 40 °C) were evaluated using a portable Raman spectrometer. After the friability test, there was no significant decrease in the peak intensity of the SERS signal (PH) for authentication in all samples. In the acceleration test, the SERS signals of the samples were attenuated, but sufficient SERS signal intensity (PH > 70) was maintained in the seven types of coating for authentication. These results demonstrate that the microtaggant NB has the potential to be used for a wide range of coating tablets.

In situ fluorescence yield soft X-ray absorption spectroscopy of electrochemical nickel deposition processes with and without ethylene glycol.

The electrochemical Ni deposition at a platinum electrode was investigated in a plating nickel bath in the presence and absence of ethylene glycol (EG) using fluorescence yield soft X-ray absorption spectroscopy (FY-XAS) in the Ni L2,3-edge and O K-edge regions under potential control. At ≤+0.35 V vs. the reversible hydrogen electrode (RHE), the electrochemical Ni deposition was detected by the Ni L2,3-edge FY-XAS in the presence of EG whereas almost no such event was observed in the absence of EG. A drastic decrease of FY-XAS intensities in the O K-edge region was also observed in the presence of EG at >+0.35 V vs. RHE, suggesting that the nano-/micro-structured Ni deposition initiated by the removal of water molecules occurs on the Pt electrode. The complex formation of Ni2+ with EG and the adsorption of EG on the Ni surface could play an important role in the Ni deposition. This study demonstrates that the in situ FY-XAS is a powerful and surface-sensitive technique to understand (electro)chemical reactions including polyol synthesis and electrocatalysis at solid-liquid interfaces.

Physically unclonable functions taggant for universal steganographic prints.

Counterfeiting of financial cards and marketable securities is a major social problem globally. Electronic identification and image recognition are common anti-counterfeiting techniques, yet they can be overcome by understanding the corresponding algorithms and analysis methods. The present work describes a physically unclonable functions taggant, in an aqueous-soluble ink, based on surface-enhanced Raman scattering of discrete self-assemblies of Au nanoparticles. Using this stealth nanobeacon, we detected a fingerprint-type Raman spectroscopy signal that we clearly identified even on a business card with a pigment mask such as copper-phthalocyanine printed on it. Accordingly, we have overcome the reverse engineering problem that is otherwise inherent to analogous anti-counterfeiting techniques. One can readily tailor the ink to various information needs and application requirements. Our stealth nanobeacon printing will be particularly useful for steganography and provide a sensitive fingerprint for anti-counterfeiting.

X-ray Photoemission Spectroscopy Study of Uniaxial Magnetic Anisotropy Induced in a Ni Layer Deposited on a LiNbO3 Substrate.

The competition between magnetic shape anisotropy and the induced uniaxial magnetic anisotropy in the heterojunction between a ferromagnetic layer and a ferroelectric substrate serves to control magnetic domain structures as well as magnetization reversal characteristics. The uniaxial magnetic anisotropy, originating from the symmetry breaking effect in the heterojunction, plays a significant role in modifying the characteristics of magnetization dynamics. Magnetoelastic phenomena are known to generate uniaxial magnetic anisotropy; however, the interfacial electronic states that may contribute to the uniaxial magnetic anisotropy have not yet been adequately investigated. Here, we report experimental evidence concerning the binding energy change in the ferromagnetic layer/ferroelectric substrate heterojunction using X-ray photoemission spectroscopy. The binding energy shifts, corresponding to the chemical shifts, reveal the binding states near the interface. Our results shed light on the origin of the uniaxial magnetic anisotropy induced from the heterojunction. This knowledge can provide a means for the simultaneous control of magnetism, mechanics, and electronics in a nano/microsystem consisting of ferromagnetic/ferroelectric materials.

Non-Destructive Imaging on Synthesised Nanoparticles.

Our recently developed non-destructive imaging technique was applied for the characterisation of nanoparticles synthesised by X-ray radiolysis and the sol-gel method. The interfacial conditions between the nanoparticles and the substrates were observed by subtracting images taken by scanning electron microscopy at controlled electron acceleration voltages to allow backscattered electrons to be generated predominantly below and above the interfaces. The interfacial adhesion was found to be dependent on the solution pH used for the particle synthesis or particle suspension preparation, proving the change in the particle formation/deposition processes with pH as anticipated and agreed with the prediction based on the Derjaguin-Landau-Verwey-Overbeek (DLVO) theory. We found that our imaging technique was useful for the characterisation of interfaces hidden by nanoparticles to reveal the formation/deposition mechanism and can be extended to the other types of interfaces.

Visualization of elemental distributions and local analysis of element-specific chemical states of an Arachnoidiscus sp. frustule using soft X-ray spectromicroscopy.

Using soft X-ray (SX) spectromicroscopy, we show maps of the spatial distribution of constituent elements and local analysis of the density of states (DOS) related to the element-specific chemical states of diatom frustules, which are composed of naturally grown nanostructured hydrogenated amorphous silica. We applied X-ray photoemission electron microscopy (X-PEEM) as well as microprobe X-ray fluorescence (µXRF) analysis to characterize the surfaces of diatom frustules by means of X-ray absorption spectroscopy (XAS) and X-ray emission spectroscopy (XES). We successfully demonstrated that SX spectromicroscopy is able to participate in potential observation tools as a new method to spectroscopically investigate diatom frustules.

Gold Nanoparticles Enhance EGFR Inhibition and Irradiation Effects in Head and Neck Squamous Carcinoma Cells.

Cetuximab, an epidermal growth factor receptor inhibitor (EI), is currently the only targeted molecular therapy used in combination with radiotherapy for head and neck squamous cell carcinoma (HNSCC). Gold nanoparticles (AuNPs) are expected to enhance radiotherapy effects in cancers. To investigate whether AuNPs combined with AG1478, an EI, enhanced irradiation effects on HNSCC cells, we first examined AG1478 adsorption on AuNP surfaces, using surface-enhanced Raman scattering, which indicated an adsorption equilibrium of AG1478 to AuNPs. We then used transmission electron microscopy to find internalization rates of AuNP alone and AuNP+AG1478; we found that intracellular uptake of AuNP alone and AuNP+AG1478 did not significantly differ. We compared cell numbers, proliferation, apoptosis, and migration between control cells and those treated with or without 60 nm AuNP (1.0 nM), AG1478 (0.5 µM), and irradiation (4 Gy). We found that AuNP+AG1478 inhibited proliferation more than AG1478 alone; the combination of irradiation+AuNP+AG1478 significantly reduced total cell numbers compared with the combination of irradiation+AuNP; AuNP+AG1478 increased apoptotic reaction to irradiation; the combinations of AuNP+AG1478 and irradiation+AuNP induced more apoptosis than AG1478+irradiation. Whereas AuNP+AG1478 enhanced cytotoxicity in human HNSCC cells by inhibiting proliferation, irradiation+AuNP enhanced cytotoxicity by inducing apoptosis.

A lab in a bento box: an autonomous centrifugal microfluidic system for an enzyme-linked immunosorbent assay.

In this paper, we report on the demonstration of a portable immunoassay system consisting of a small centrifugal microfluidic device driver (bento box) and a centrifugal microfluidic device made of polypropylene and fabricated by injection molding. The bento box consists of a cheap DC motor and an Arduino microcontroller. It has a simple structure and is the size of a bento box, that is, 150 × 150 × 100 (W × D × H) mm3. The developed device can automatically execute an enzyme-linked immunosorbent assay (ELISA) process under a steady rotating condition because it was designed based on the principle of CLOCK, which we previously presented. Here, we first executed an ELISA using a system consisting of the bento box and a device made of polydimethylsiloxane (PDMS) and compared it with a servo-controlled device driver. It was confirmed that the results of the bento box were consistent with those of the servo-controlled device driver. The limit of detection (LOD) using the bento box was 0.759 ng ml-1. Therefore, the controllability of the bento box was demonstrated. Next, we evaluated the injection-molded device through multi-step fluid control. We confirmed, through real-time observation of the device, that accurate flow control in the designed ELISA procedure was executed. Lastly, ELISA was employed for the measurements of mouse IgG using the system consisting of the bento box and the polypropylene device. The system performed all fluidic controls within 12 min; we confirmed the specificity of the system, and the LOD was 0.320 ng ml-1.

Solid/liquid-interface-dependent synthesis and immobilization of copper-based particles nucleated by X-ray-radiolysis-induced photochemical reaction.

X-ray-radiolysis-induced photochemical reaction of a liquid solution enables the direct synthesis and immobilization of nano/micro-scale particles and their aggregates onto a desired area. As is well known, the synthesis, growth and aggregation are dependent on the pH, additives and X-ray irradiation conditions. In this study, it was found that the topography and composition of synthesized particles are also dependent on the types of substrate dipped in an aqueous solution of Cu(COOCH3)2 in the X-ray-radiolysis-induced photochemical reaction. These results are attributed to the fact that a secondary electron induced by the X-ray irradiation, surface or interface on which the particles are nucleated and grown influences the particle shape and composition. This study will shed light on understanding a novel photochemical reaction route induced under X-ray irradiation. The development of this process using the X-ray-radiolysis-induced photochemical reaction in aqueous liquids enables us to achieve the rapid and easy operation of the synthesis, growth and immobilization of special nano/micro-scale complex materials or multifunctional composites.

Controllability of cupric particle synthesis by linear alcohol chain number as additive and pH control in cupric acetate solution using X-ray radiolysis.

Synthesis and immobilization of caltrop cupric particles onto a Si substrate using X-ray radiolysis directly from a liquid solution of Cu(COOCH3)2 is demonstrated. Caltrop cupric oxide particles are formed in the X-ray radiolysis of aqueous solutions of Cu(COOCH3)2, which also contain methanol, ethanol, 2-propanol or 1-propanol as ^\bulletOH scavenger. The blade lengths of the caltrop particles are dependent on the alcohol chain length. In particular, it was found that an alkyl alcohol whose chain length is longer than four is unable to synthesize any particles in aqueous solutions of Cu(COOCH3)2 in X-ray radiolysis. These results are attributed to the alkyl alcohol chain length influencing the rate of reaction of radicals and determines the solvable ratio of its alcohol into water. In addition, it was found that the synthesized particle geometric structure and composition can also be controlled by the pH of the aqueous solution in the X-ray radiolysis. This study may open a door to understanding and investigating a novel photochemical reaction route induced under X-ray irradiation. The development of the X-ray radiolysis process enables us to achieve the rapid and easy process of synthesis and immobilization of higher-order nano/microstructure consisting of various materials.

Deep X-ray lithography system with a uniform and high-accuracy fabrication area established in beamline BL11 at NewSUBARU.

A new lithography system to fabricate high-aspect-ratio 3D microstructures was developed at the NewSUBARU synchrotron radiation facility (University of Hyogo, Japan). The X-ray beam generated by this system has high parallelism (horizontal and vertical divergence angles of 278 µrad and 14 µrad, respectively) and high photon flux (31 mW mm-2 at a beam current of 300 mA). The high photon flux and exposure area of the system were validated and a beam-scan method for a large exposure area with a uniform dose distribution has been proposed. In addition, the deep X-ray lithography performance was characterized using a conventional photosensitive material and the synchrotron-radiation-induced direct etching of polytetrafluoroethylene (PTFE) was demonstrated. An enlargement of the microfabrication area up to 100 mm × 100 mm while contemporarily ensuring high uniformity was achieved.

Caltrop particles synthesized by photochemical reaction induced by X-ray radiolysis.

X-ray radiolysis of a Cu(CH3COO)2 solution was observed to produce caltrop-shaped particles of cupric oxide (CuO, Cu2O), which were characterized using high-resolution scanning electron microscopy and micro-Raman spectrometry. X-ray irradiation from a synchrotron source drove the room-temperature synthesis of submicrometer- and micrometer-scale cupric oxide caltrop particles from an aqueous Cu(CH3COO)2 solution spiked with ethanol. The size of the caltrop particles depended on the ratio of ethanol in the stock solution and the surface of the substrate. The results indicated that there were several synthetic routes to obtain caltrop particles, each associated with electron donation. The technique of X-ray irradiation enables the rapid synthesis of caltrop cupric oxide particles compared with conventional synthetic methods.

Quasi-omnidirectional electrical spectrometer for studying spin dynamics in magnetic tunnel junctions.

We report an omnidirectional electrical spectroscopy setup for studying the spin dynamics in a nanoscale magnet. It has a measureable solid angle range comprising about 50% of the total range and allows the magnetoresistance and spin-torque diode signal to be measured simultaneously at any angle to the magnetization. This setup can provide detailed information about the spin-wave resonance modes excited in a nanoscale magnet.

A silicon metal-oxide-semiconductor field-effect transistor Hall bar for scanning Hall probe microscopy.

We demonstrate successful operation of a scanning Hall probe microscope with a few micron-size resolution by using a silicon metal-oxide semiconductor field-effect transistor (Si-MOSFET) Hall bar, which is designed to improve not only the mechanical strength but also the temperature stability. The Si-MOSFET micro-Hall probe is cheaper than the current micro-Hall probes and is found to be as sensitive as a micro-Hall probe with GaAs/AlGaAs heterostructure or an epitaxial InSb two-dimensional electron gas. This was used to magnetically image the surface of a Sm(2)Co(17) permanent magnet during the magnetization reversal process as a function of an external magnetic field below 1.5 T. This revealed firm evidence of the presence of the inverse magnetic seed as theoretically predicted earlier. Magnetically pinned centers, with a typical size 80 mum, are observed to persist even under a high magnetic field, clearly indicating the robustness of the Si Hall probe against the field application as well as the repetition of the measurement.