High-density adherent culture of CHO cells using rolled scaffold bioreactor.

Rapid expansion of biopharmaceutical market calls for more efficient and reliable platforms to culture mammalian cells on a large scale. Stirred-tank bioreactors have been widely used for large-scale cell culture. However, it requires months of trials and errors to optimize culture conditions for each cell line. In this article, we extend our earlier studies on rolled scaffold (RS) bioreactors for high-density adherent cell culture and report two new implementations of RSs with greatly enhanced mass-manufacturability, termed as Mesh-RS and Fiber-RS. CHO-K1 cells were successfully expanded in Mesh-RS and Fiber-RS bioreactors with an average growth rate of 1.09 ± 0.04 1/day and 0.95 ± 0.07 1/day, which were higher than those reported in similar studies. Fiber-RS bioreactor exhibited a very high cell density of 72.8 × 106 cells/ml. Besides, a dialyzer was integrated into the RS bioreactor to remove cellular waste and to replenish nutrients without disturbing the cells. By collecting the dialyzed media separately, the dialysis efficiency was significantly improved. In conclusion, the developed RS bioreactor has a strong potential to provide a highly reliable and easily scalable platform for large-scale cell culture in the biopharmaceutical industry.

Anisotropic 2D SiAs for High-Performance UV-Visible Photodetectors.

Recently, extensive efforts have been directed at finding novel 2D-layered structures with anisotropic crystal structures. Herein, the in-plane anisotropic optical and (photo)electrical properties of 2D SiAs nanosheets synthesized using a solid-state reaction and subsequent mechanical exfoliation are reported. The angle-resolved polarized Raman spectrum shows high in-plane anisotropy of the phonon vibration modes, which are consistent with the theoretical prediction. Field-effect transistor devices fabricated using the SiAs nanosheets demonstrate significant anisotropy in the hole mobility with an anisotropic ratio as high as 5.5. Photodetectors fabricated with single SiAs nanosheet exhibit high sensitivity in the UV-visible region, and the anisotropic ratio of the photocurrent reaches 5.3 at 514.5 nm and 2.3 at 325 nm. This work lays the foundation for future research in anisotropic 2D materials.

Modelling the expected impact of cigarette tax and price increases under Vietnam's excise tax law 2015-2020.

BACKGROUND: Vietnam's national tobacco control strategy aims to reduce the rate of smoking among male adults from 45% in 2015 to 39% by 2020. The aim of this paper is to assess what contribution cigarette tax increases under Vietnam's current excise tax plan can be expected to make to this target, and to discuss what additional measures might be implemented accordingly. METHODS: This study uses a mix of administrative datasets and predictive modelling techniques to assess the expected impact of tax and price increases on cigarette consumption, tobacco tax revenues and the rate of smoking between 2015 and 2020. FINDINGS: The average retail price of cigarettes is estimated to have increased by 16% (sensitivity analysis: 14%-18%) in inflation-adjusted terms between 2015 and 2020, while cigarette consumption is projected to decrease by 5.1% (4.5%-5.5%). The rate of smoking among males is projected to decrease to 42.8% (42.1%-43.6%) compared with the target of 39%. Total tax revenues from cigarettes are projected to increase by 21% (19%-23%), reflecting an extra ₫3300 billion in inflation-adjusted revenues for the government. CONCLUSION: The current excise tax law is expected to have only a modest impact on the rate of smoking in Vietnam, though it has generated tax revenues. If Vietnam is to achieve its tobacco control targets, the government should implement a mixed excise system with a high-specific component to promote public health by raising the price of cigarettes more significantly.

Early Essential Newborn Care can still be used with mothers who have COVID-19 if effective infection control measures are applied.

We describe the first infant born to a woman with COVID-19 in Vietnam, by Caesarean section at 36 weeks and 5 days of gestation. The mother and baby remained together during their hospital stay and prolonged skin-to-skin contact and early and exclusive breastfeeding were achieved. This was in line with the World Health Organization's Early Essential Newborn Care (EENC) recommendations, the national Vietnamese standard of care since 2014. The baby remained virus-free throughout the 34-day postpartum follow-up. CONCLUSION: The EENC approach can still be used with mothers who have COVID-19 if effective infection control measures are applied.

Phase Controlled Growth of Cd3As2 Nanowires and Their Negative Photoconductivity.

The bottom-up synthesis process often allows the growth of metastable phase nanowires instead of the thermodynamically stable phase. Herein, we synthesized Cd3As2 nanowires with a controlled three-dimensional Dirac semimetal phase using a chemical vapor transport method. Three different phases such as the body centered tetragonal (bct), and two metastable primitive tetragonal (P42/nbc and P42/nmc) phases were identified. The conversion between three phases (bct → P42/nbc → P42/nmc) was achieved by increasing the growth temperature. The growth direction is [110] for bct and P42/nbc and [100] for P42/nmc, corresponding to the same crystallographic axis. Field effect transistors and photodetector devices showed the nearly same electrical and photoelectrical properties for three phases. Differential conductance measurement confirms excellent electron mobility (2 × 104 cm2/(V s) at 10 K). Negative photoconductance was first observed, and the photoresponsivity reached 3 × 104 A/W, which is ascribed to the surface defects acting as trap sites for the photogenerated electrons.

Controllable p-n junctions in three-dimensional Dirac semimetal Cd3As2 nanowires.

We demonstrate a controllable p-n junction in a three-dimensional Dirac semimetal (DSM) Cd3As2 nanowire with two recessed bottom gates. The device exhibits four different conductance regimes with gate voltages, the unipolar (n-n and p-p) and bipolar (n-p and n-p) regimes, where p-n junctions are formed. The conductance in the p-n junction regimes decreases drastically when a magnetic field is applied perpendicular to the nanowire. In these regimes, the device shows quantum dot behavior, whereas the device exhibits conductance plateaus in the n-n regime at high magnetic fields. Our experiment shows that the ambipolar tunability of DSM nanowires can enable the realization of quantum devices based on quantum dots and electron optics.

Static microdroplet array generated by spraying and analyzed with automated microscopy and image processing.

Microdroplets have received increasing interest as practical platforms for high-throughput biochemical analysis. Typically, numerous discrete aqueous microdroplets containing biochemical targets are generated in a continuous oil phase and characterized using a flow-through configuration. Although this approach is capable of extremely high throughput, it is challenging to provide dynamic characterization of time-dependent reaction kinetics. In this paper, we present a practical and affordable method to create and analyze a massive array of static aqueous microdroplets immersed in oil for biochemical analysis. The discrete microdroplets were produced by an air-spray gun, imaged by automated microscopy, and then characterized by image processing. The location, area, and fluorescence intensity of randomly generated individual microdroplets were automatically registered for high-throughput characterization. With this approach, we rapidly produced and characterized a static microdroplet array of over 0.7 million microdroplets with an average volume of 300 fL and a mean population density of 1.5*105 microdroplets/cm2. Using the developed setup, we demonstrated the dependency of the microdroplets' fluorescence intensity on their volume, as well as characterized the time-dependent enzyme reaction kinetics of ß-galactosidase-mediated cleavage of the substrate fluorescein di-ß-d-galactopyranoside (FDG). The new approach described herein provides an inexpensive alternative solution for high-throughput analysis of dynamic biochemical processes.

Development of rolled scaffold for high-density adherent cell culture.

Bioreactors for large-scale culture of mammalian cells are playing vital roles in biotechnology and bioengineering. Various bioreactors have been developed, but their capacity and efficiency are often limited by insufficient mass transfer rate and high shear stress. A rolled scaffold (RS) is a fully defined scaffold for high-density adherent culture of mammalian cells. The RS is a polymer film with spacers, that is rolled into a cylinder with a pre-determined gap between each turn. Cells are cultured on its inner surfaces, while media flows through the gap. The RS exhibits high surface-area-to-volume ratio over 100 cm2/mL and can transport nutrients and gases with significantly reduced shear stress via convection in a unidirectional laminar flow, rather than diffusion and random turbulent flow as in stirred-tank bioreactors. In this paper, we expanded Chinese Hamster Ovary cells with RS bioreactors and demonstrated cell culture density over 60 million cells/mL with a growth rate higher than conventional suspension culture. Besides, murine embryonic stem cells were successfully expanded without losing their pluripotency. The RS will provide an affordable, scalable, and reliable platform for large-scale culture of recombinant cells in biopharmaceutical industries and shear-sensitive stem cells for tissue engineering.

Quantum Dots Formed in Three-dimensional Dirac Semimetal Cd3As2 Nanowires.

We demonstrate quantum dot (QD) formation in three-dimensional Dirac semimetal Cd3As2 nanowires using two electrostatically tuned p-n junctions with a gate and magnetic fields. The linear conductance measured as a function of gate voltage under high magnetic fields is strongly suppressed at the Dirac point close to zero conductance, showing strong conductance oscillations. Remarkably, in this regime, the Cd3As2 nanowire device exhibits Coulomb diamond features, indicating that a clean single QD forms in the Dirac semimetal nanowire. Our results show that a p-type QD can be formed between two n-type leads underneath metal contacts in the nanowire by applying gate voltages under strong magnetic fields. Analysis of the quantum confinement in the gapless band structure confirms that p-n junctions formed between the p-type QD and two neighboring n-type leads under high magnetic fields behave as resistive tunnel barriers due to cyclotron motion, resulting in the suppression of Klein tunneling. The p-type QD with magnetic field-induced confinement shows a single hole filling. Our results will open up a route to quantum devices such as QDs or quantum point contacts based on Dirac and Weyl semimetals.

Hollow microcarriers for large-scale expansion of anchorage-dependent cells in a stirred bioreactor.

With recent advances in biotechnology, mammalian cells are used in biopharmaceutical industries to produce valuable protein therapeutics and investigated as effective therapeutic agents to permanently degenerative diseases in cell based therapy. In these exciting and actively expanding fields, a reliable, efficient, and affordable platform to culture mammalian cells on a large scale is one of the most vital necessities. To produce and maintain a very large population of anchorage-dependent cells, a microcarrier-based stirred tank bioreactor is commonly used. In this approach, the cells are exposed to harmful hydrodynamic shear stress in the bioreactor and the mass transfer rates of nutrients and gases in the bioreactor are often kept below an optimal level to prevent cellular damages from the shear stress. In this paper, a hollow microcarrier (HMC) is presented as a novel solution to protect cells from shear stress in stirred bioreactors, while ensuring sufficient and uniform mass transfer rate of gases and nutrients. HMC is a hollow microsphere and cells are cultured on its inner surface to be protected, while openings on the HMC provide sufficient exchange of media inside the HMC. As a proof of concept, we demonstrated the expansion of fibroblasts, NIH/3T3 and the expansion and cardiac differentiation of human induced pluripotent stem cells, along with detailed numerical analysis. We believe that the developed HMC can be a practical solution to enable large-scale expansion of shear-sensitive anchorage-dependent cells in an industrial scale with stirred bioreactors.

Enhanced Moisture-Reactive Hydrophilic-PTFE-Based Flexible Humidity Sensor for Real-Time Monitoring.

Flexible sensors connected to cell phones are a promising technology that can aid in continuously monitoring signals in our daily lives, such as an individual's health status and information from buildings, farms, and industry. Among such signals, real-time humidity monitoring is crucial to a comfortable life, as human bodies, plants, and industrial environments require appropriate humidity to be maintained. We propose a hydrophilic polytetrafluoroethylene (H-PTFE)-based flexible humidity sensor integrated with readout circuitry, wireless communication, and a mobile battery. To enhance its sensitivity, linearity, and reliability, treatment with sodium hydroxide implements additional hydroxyl (OH) groups, which further enhance the sensitivity, create a strong linearity with respect to variations in relative humidity, and produce a relatively free hysteresis. Furthermore, to create robust mechanical stability, cyclic upward bending was performed for up to 3000 cycles. The overall electrical and mechanical results demonstrate that the flexible real-time H-PTFE humidity sensor system is suitable for applications such as wearable smart devices.

Multifrequency Optomechanical Stiffness Measurement of Single Adherent Cells on a Solid Substrate with High Throughput.

Mechanical properties of a cell reflect its biological and pathological conditions and there have been active research efforts to develop high-throughput platforms to mechanically characterize single cells. Yet, many of these research efforts are focused on suspended cells and use a flow-through configuration. In this paper, the stiffness of single adherent cells are optomechanically characterized using the vibration-induced phase shift (VIPS) without detaching them from the substrate. With the VIPS measurements, the frequency and amplitude dependency of the cell stiffness is investigated and statistically significant difference in the cell stiffness is confirmed after exposure to various drugs affecting cytoskeleton network. Furthermore, a 3-dimensional finite element model of a cell on a vibrating substrate is developed to extract the mechanical property from the measured VIPS. The developed technique can characterize the mechanical properties of single adherent cells at multiple frequencies with high throughput and will provide valuable clues in understanding cell mechanics.

Bent Polytypic ZnSe and CdSe Nanowires Probed by Photoluminescence.

Nanowires (NWs) have witnessed tremendous development over the past two decades owing to their varying potential applications. Semiconductor NWs often contain stacking faults due to the presence of coexisting phases, which frequently hampers their use. Herein, it is investigated how stacking faults affect the optical properties of bent ZnSe and CdSe NWs, which are synthesized using the vapor transport method. Polytypic zinc blende-wurtzite structures are produced for both these NWs by altering the growth conditions. The NWs are bent by the mechanical buckling of poly(dimethylsilioxane), and micro-photoluminescence (PL) spectra were then collected for individual NWs with various bending strains (0-2%). The PL measurements show peak broadening and red shifts of the near-band-edge emission as the bending strain increases, indicating that the bandgap decreases with increasing the bending strain. Remarkably, the bandgap decrease is more significant for the polytypic NWs than for the single phase NWs. This work provides insights into flexible electronic devices of 1D nanostructures by engineering the polytypic structures.

Measurement of cell traction force with a thin film PDMS cantilever.

Adherent cells produce cellular traction force (CTF) on a substrate to maintain their physical morphologies, sense external environment, and perform essential cellular functions. Precise characterization of the CTF can expand our knowledge of various cellular processes as well as lead to the development of novel mechanical biomarkers. However, current methods that measure CTF require special substrates and fluorescent microscopy, rendering them less suitable in a clinical setting. Here, we demonstrate a rapid and direct approach to measure the combined CTF of a large cell population using thin polydimethylsiloxane (PDMS) cantilevers. Cells attached to the top surface of the PDMS cantilever produce CTF, which causes the cantilever to bend. The side view of the cantilever was imaged with a low-cost camera to extract the CTF. We characterized the CTF of fibroblasts and breast cancer cells. In addition, we were able to directly measure the contractile force of a suspended cell sheet, which is similar to the CTF of the confluent cell layer before detachment. The demonstrated technique can provide rapid and real-time measurement of the CTF of a large cell population and can directly characterize its temporal dynamics. The developed thin film PDMS cantilever can be fabricated affordably and the CTF extraction technique does not require expensive equipment. Thus, we believe that the developed method can provide an easy-to-use and affordable platform for CTF characterization in clinical settings and laboratories.

Fabrication and characterization of self-folding thermoplastic sheets using unbalanced thermal shrinkage.

Self-folding or micro-origami technologies are actively investigated as a novel manufacturing process to fabricate three-dimensional macro/micro-structures. In this paper, we present a simple process to produce a self-folding structure with a biaxially oriented polystyrene sheet (BOPS) or Shrinky Dinks. A BOPS sheet is known to shrink to one-third of its original size in plane, when it is heated above 160 °C. A grid pattern is engraved on one side of the BOPS film with a laser engraver to decrease the thermal shrinkage of the engraved side. The thermal shrinkage of the non-engraved side remains the same and this unbalanced thermal shrinkage causes folding of the structure as the structure shrinks at high temperature. We investigated the self-folding mechanism and characterized how the grid geometry, the grid size, and the power of the laser engraver affect the bending curvature. The developed fabrication process to locally modulate thermomechanical properties of the material by engraving the grid pattern and the demonstrated design methodology to harness the unbalanced thermal shrinkage can be applied to develop complicated self-folding macro/micro structures.

Schottky nanocontact of one-dimensional semiconductor nanostructures probed by using conductive atomic force microscopy.

To develop the advanced electronic devices, the surface/interface of each component must be carefully considered. Here, we investigate the electrical properties of metal-semiconductor nanoscale junction using conductive atomic force microscopy (C-AFM). Single-crystalline CdS, CdSe, and ZnO one-dimensional nanostructures are synthesized via chemical vapor transport, and individual nanobelts (or nanowires) are used to fabricate nanojunction electrodes. The current-voltage (I -V) curves are obtained by placing a C-AFM metal (PtIr) tip as a movable contact on the nanobelt (or nanowire), and often exhibit a resistive switching behavior that is rationalized by the Schottky (high resistance state) and ohmic (low resistance state) contacts between the metal and semiconductor. We obtain the Schottky barrier height and the ideality factor through fitting analysis of the I-V curves. The present nanojunction devices exhibit a lower Schottky barrier height and a higher ideality factor than those of the bulk materials, which is consistent with the findings of previous works on nanostructures. It is shown that C-AFM is a powerful tool for characterization of the Schottky contact of conducting channels between semiconductor nanostructures and metal electrodes.

Zn3P2-Zn3As2 solid solution nanowires.

Semiconductor alloy nanowires (NWs) have recently attracted considerable attention for applications in optoelectronic nanodevices because of many notable properties, including band gap tunability. Zinc phosphide (Zn3P2) and zinc arsenide (Zn3As2) belong to a unique pseudocubic tetragonal system, but their solid solution has rarely been studied. Here In this study, we synthesized composition-tuned Zn3(P1-xAsx)2 NWs with different crystal structures by controlling the growth conditions during chemical vapor deposition. A first type of synthesized NWs were single-crystalline and grew uniformly along the [110] direction (in a cubic unit cell) over the entire compositional range (0 ≤ x ≤ 1) explored. The use of an indium source enabled the growth of a second type of NWs, with remarkable cubic-hexagonal polytypic twinned superlattice and bicrystalline structures. The growth direction of the Zn3P2 and Zn3As2 NWs was also switched to [111] and [112], respectively. These structural changes are attributable to the Zn-depleted indium catalytic nanoparticles which favor the growth of hexagonal phases. The formation of a solid solution at all compositions allowed the continuous tuning of the band gap (1.0-1.5 eV). Photocurrent measurements were performed on individual NWs by fabricating photodetector devices; the single-crystalline NWs with [110] growth direction exhibit a higher photoconversion efficiency compared to the twinned crystalline NWs with [111] or [112] growth direction.

Reversible Halide Exchange Reaction of Organometal Trihalide Perovskite Colloidal Nanocrystals for Full-Range Band Gap Tuning.

In recent years, methylammonium lead halide (MAPbX3, where X = Cl, Br, and I) perovskites have attracted tremendous interest caused by their outstanding photovoltaic performance. Mixed halides have been frequently used as the active layer of solar cells, as a result of their superior physical properties as compared to those of traditionally used pure iodide. Herein, we report a remarkable finding of reversible halide-exchange reactions of MAPbX3, which facilitates the synthesis of a series of mixed halide perovskites. We synthesized MAPbBr3 plate-type nanocrystals (NCs) as a starting material by a novel solution reaction using octylamine as the capping ligand. The synthesis of MAPbBr(3-x)Clx and MAPbBr(3-x)Ix NCs was achieved by the halide exchange reaction of MAPbBr3 with MACl and MAI, respectively, in an isopropyl alcohol solution, demonstrating full-range band gap tuning over a wide range (1.6-3 eV). Moreover, photodetectors were fabricated using these composition-tuned NCs; a strong correlation was observed between the photocurrent and photoluminescence decay time. Among the two mixed halide perovskite series, those with I-rich composition (x = 2), where a sole tetragonal phase exists without the incorporation of a cubic phase, exhibited the highest photoconversion efficiency. To understand the composition-dependent photoconversion efficiency, first-principles density-functional theory calculations were carried out, which predicted many plausible configurations for cubic and tetragonal phase mixed halides.

In Situ Temperature-Dependent Transmission Electron Microscopy Studies of Pseudobinary mGeTe·Bi2Te3 (m = 3-8) Nanowires and First-Principles Calculations.

Phase-change nanowires (NWs) have emerged as critical materials for fast-switching nonvolatile memory devices. In this study, we synthesized a series of mGeTe·Bi2Te3 (GBT) pseudobinary alloy NWs-Ge3Bi2Te6 (m = 3), Ge4Bi2Te7 (m = 4), Ge5Bi2Te8 (m = 5), Ge6Bi2Te9 (m = 6), and Ge8Bi2Te11 (m = 8)-and investigated their composition-dependent thermal stabilities and electrical properties. As m decreases, the phase of the NWs evolves from the cubic (C) to the hexagonal (H) phase, which produces unique superlattice structures that consist of periodic 2.2-3.8 nm slabs for m = 3-8. In situ temperature-dependent transmission electron microscopy reveals the higher thermal stability of the compositions with lower m values, and a phase transition from the H phase into the single-crystalline C phase at high temperatures (400 °C). First-principles calculations, performed for the superlattice structures (m = 1-8) of GBT and mGeTe·Sb2Te3 (GST), show an increasing stability of the H phase (versus the C phase) with decreasing m; the difference in stability being more marked for GBT than for GST. The calculations explain remarkably the phase evolution of the GBT and GST NWs as well as the composition-dependent thermal stabilities. Measurement of the current-voltage curves for individual GBT NWs shows that the resistivity is in the range 3-25 mΩ·cm, and the resistivity of the H phase is lower than that of the C phase, which has been supported by the calculations.

GaP-ZnS pseudobinary alloy nanowires.

Multicomponent nanowires (NWs) are of great interest for integrated nanoscale optoelectronic devices owing to their widely tunable band gaps. In this study, we synthesize a series of (GaP)(1-x)(ZnS)(x) (0 ≤ x ≤ 1) pseudobinary alloy NWs using the vapor transport method. Compositional tuning results in the phase evolution from the zinc blende (ZB) (x < 0.4) to the wurtzite (WZ) phase (x > 0.7). A coexistence of ZB and WZ phases (x = 0.4-0.7) is also observed. In the intermediate phase coexistence range, a core-shell structure is produced with a composition of x = 0.4 and 0.7 for the core and shell, respectively. The band gap (2.4-3.7 eV) increases nonlinearly with increasing x, showing a significant bowing phenomenon. The phase evolution leads to enhanced photoluminescence emission. Strikingly, the photoluminescence spectrum shows a blue-shift (70 meV for x = 0.9) with increasing excitation power, and a wavelength-dependent decay time. Based on the photoluminescence data, we propose a type-II pseudobinary heterojunction band structure for the single-crystalline WZ phase ZnS-rich NWs. The slight incorporation of GaP into the ZnS induces a higher photocurrent and excellent photocurrent stability, which opens up a new strategy for enhancing the performance of photodetectors.