Field-effect at electrical contacts to two-dimensional materials.

The inferior electrical contact to two-dimensional (2D) materials is a critical challenge for their application in post-silicon very large-scale integrated circuits. Electrical contacts were generally related to their resistive effect, quantified as contact resistance. With a systematic investigation, this work demonstrates a capacitive metal-insulator-semiconductor (MIS) field-effect at the electrical contacts to 2D materials: The field-effect depletes or accumulates charge carriers, redistributes the voltage potential, and gives rise to abnormal current saturation and nonlinearity. On one hand, the current saturation hinders the devices' driving ability, which can be eliminated with carefully engineered contact configurations. On the other hand, by introducing the nonlinearity to monolithic analog artificial neural network circuits, the circuits' perception ability can be significantly enhanced, as evidenced using a coronavirus disease 2019 (COVID-19) critical illness prediction model. This work provides a comprehension of the field-effect at the electrical contacts to 2D materials, which is fundamental to the design, simulation, and fabrication of electronics based on 2D materials. ELECTRONIC SUPPLEMENTARY MATERIAL: Supplementary material (results of the simulation and SEM) is available in the online version of this article at 10.1007/s12274-021-3670-y.

Ultrathin Three-Monolayer Tunneling Memory Selectors.

High-density memory arrays require selector devices, which enable selection of a specific memory cell within a memory array by suppressing leakage current through unselected cells. Such selector devices must have highly nonlinear current-voltage characteristics and excellent endurance; thus selectors based on a tunneling mechanism present advantages over those based on the physical motion of atoms or ions. Here, we use two-dimensional (2D) materials to build an ultrathin (three-monolayer-thick) tunneling-based memory selector. Using a sandwich of h-BN, MoS2, and h-BN monolayers leads to an "H-shaped" energy barrier in the middle of the heterojunction, which nonlinearly modulates the tunneling current when the external voltage is varied. We experimentally demonstrate that tuning the MoS2 Fermi level can improve the device nonlinearity from 10 to 25. These results provide a fundamental understanding of the tunneling process through atomically thin 2D heterojunctions and lay the foundation for developing high endurance selectors with 2D heterojunctions, potentially enabling high-density non-volatile memory systems.

Graphene and two-dimensional materials for silicon technology.

The development of silicon semiconductor technology has produced breakthroughs in electronics-from the microprocessor in the late 1960s to early 1970s, to automation, computers and smartphones-by downscaling the physical size of devices and wires to the nanometre regime. Now, graphene and related two-dimensional (2D) materials offer prospects of unprecedented advances in device performance at the atomic limit, and a synergistic combination of 2D materials with silicon chips promises a heterogeneous platform to deliver massively enhanced potential based on silicon technology. Integration is achieved via three-dimensional monolithic construction of multifunctional high-rise 2D silicon chips, enabling enhanced performance by exploiting the vertical direction and the functional diversification of the silicon platform for applications in opto-electronics and sensing. Here we review the opportunities, progress and challenges of integrating atomically thin materials with silicon-based nanosystems, and also consider the prospects for computational and non-computational applications.

Unipolar n-Type Black Phosphorus Transistors with Low Work Function Contacts.

Black phosphorus (BP) is a promising two-dimensional (2D) material for nanoscale transistors, due to its expected higher mobility than other 2D semiconductors. While most studies have reported ambipolar BP with a stronger p-type transport, it is important to fabricate both unipolar p- and n-type transistors for low-power digital circuits. Here, we report unipolar n-type BP transistors with low work function Sc and Er contacts, demonstrating a record high n-type current of 200 µA/µm in 6.5 nm thick BP. Intriguingly, the electrical transport of the as-fabricated, capped devices changes from ambipolar to n-type unipolar behavior after a month at room temperature. Transmission electron microscopy analysis of the contact cross-section reveals an intermixing layer consisting of partly oxidized metal at the interface. This intermixing layer results in a low n-type Schottky barrier between Sc and BP, leading to the unipolar behavior of the BP transistor. This unipolar transport with a suppressed p-type current is favorable for digital logic circuits to ensure a lower off-power consumption.

Vertical and Lateral Copper Transport through Graphene Layers.

A different mechanism was found for Cu transport through multi-transferred single-layer graphene serving as diffusion barriers on the basis of time-dependent dielectric breakdown tests. Vertical and lateral transport of Cu dominates at different stress electric field regimes. The classic E-model was modified to project quantitatively the effectiveness of the graphene Cu diffusion barrier at low electric field based on high-field accelerated stress data. The results are compared to industry-standard Cu diffusion barrier material TaN. 3.5 Å single-layer graphene shows the mean time-to-fail comparable to 4 nm TaN, while two-time and three-time transferred single-layer graphene stacks give 2× and 3× improvements, respectively, compared to single-layer graphene at a 0.5 MV/cm electric field. The influences of graphene grain boundaries on Cu vertical transport through the graphene layers are explored, revealing that large-grain (10-15 µm) single-layer graphene gives a 2 orders of magnitude longer lifetime than small-grain (2-3 µm) graphene. As a result, it is more effective to further enhance graphene barrier reliability by improving single-layer graphene quality through increasing grain sizes or using single-crystalline graphene than just by increasing thickness through multi-transfer. These results may also be applied for graphene as barriers for other metals.

Application of open porous poly(D,L-lactide-co-glycolide) microspheres and the strategy of hydrophobic seeding in hepatic tissue cultivation.

In this article, porous poly(D,L-lactide-co-glycolide) (PLGA) microsphere scaffolds with a size of ∼ 400 µm and pores of ∼ 20 µm were prepared for constructing injectable three-dimensional hepatocyte spheroids. The porous sites of PLGA microspheres provided a spatial space for hepatocyte distribution. Hepatocytes spheroids were cocultured with human umbilical vein endothelial cell, bone marrow mesenchymal stem cell, or NIH/3T3 cells by combining the porous PLGA microspheres with the relatively hydrophobic culture strategy. The combination of open porous microspheres, hepatocytes, and nonparenchymal cells was demonstrated for application in functional hepatic tissue reconstruction. Hepatocellular-specific functions can sustained up to 2 weeks in the support of coculturing with nonparenchymal cells. The spheroidal hepatocyte coculture system had the advantages of an injectable delivery, higher cell seeding density, protection from exerted shear stress, better exchange of nutrients, oxygen and metabolites, and heterotypic cell-cell contact within and between microspheres.

Pulmonary delivery of insulin by liposomal carriers.

Growing attention has been given to the potential of a pulmonary route as a non-invasive administration for systemic delivery of therapeutic agents (mainly peptides and proteins). The lungs provide a large absorptive surface area, extremely thin absorptive mucosal membrane, and good blood supply. The non-invasive nature of this pathway makes it especially valuable for the delivery of large molecular protein. However, pulmonary delivery of peptides and proteins is complicated by the complexity of the anatomic structure of the human respiratory system and the effect of disposition exerted by the respiration process. In this study, novel nebulizer-compatible liposomal carrier for aerosol pulmonary drug delivery of insulin was developed and characterized. Experimental results showed that insulin could be efficiently encapsulated into liposomes by preformed vesicles and detergent dialyzing method. The optimal encapsulation efficiency was achieved when 40% ethanol was used. The particle size of liposomal aerosols from ultrasonic nebulizer approximated to 1 mum. Insulin was stable in the liposomal solution. Animal studies showed that plasma glucose level was effectively reduced when liposomal insulin was delivered by inhalation route of using aerosolized insulin-encapsulated liposomes. Including fluorescent probe (phosphatidylethanolamine-rhodamine) into liposome, we found that the liposomal carriers were effectively and homogeneously distributed in the lung aveolar. Liposome-mediated pulmonary drug delivery promotes an increase in drug retention-time in the lungs, and more importantly, a reduction in extrapulmonary side-effects which invariably results in enhanced therapeutic efficacies.

A comparison of regional and systemic humoral immune responses to a nematode infection.

The kinetics of humoral immune response against Trichinella spiralis (TS) was characterized with immunofluorescence assay. The mesenteric lymph nodes (MLN) and the spleen of infected rats were examined for concurrent expression of multiple antibody (Ab) isotypes from day 1 to day 15 after infection. The tissues were processed and stained with either a pan-B cell marker (OX33) conjugated with rhodamine (XRITC) or combinations of dual monoclonal Ab probes plus A secondary Ab conjugated with XRITC or fluorescein (FITC). As compared to the uninfected controls, the spleen and the MLN showed significant proliferation of dual-Ab expressing B cells (Debc) on days 5 and 7, respectively. During the immune response, only minimal numbers of B cells expressed single Ab isotype while most B cells expressed more than one isotypes of Ab. When combining all the numbers of Debc within each tissue for each respective days, and comparing those numbers with the total numbers of B cells that were OX33+ in the serial sections of the same tissue specimens, the combined Debc in the spleen were > 6 times higher than the OX33 labeled B cells on day 10, and the Debc in MLN were > 3 times higher than the OX33+ B cells on day 10. Our results thus indicate that the Debc most likely expressed more than two Ab isotypes during the peak days of the humoral immune response to the parasite and this phenomenon occurred in both regional and systemic lymphoid tissues.

Rapidity and multiplicity of synthesis and expression of immunoglobulin isotypes by B lymphocytes in the small intestine.

An immunofluorescence double labeling assay was used to examine the kinetics of intestinal B lymphocytes with concurrent expression of multiple antibody isotypes in the mucosal tissues of rats infected with Trichinella spiralis (TS) muscle larvae for 1 to 15 days. As compared to the uninfected controls (day 0), the non-Peyer's patch tissues of the small intestine contained a significantly increased number of dual antibody-expressing B cells as early as 3 days after infection with a maximum proliferation of these B cells on days 7 and 10. These results indicate the rapidity of B cell response in the small intestine. Similar results were observed in the germinal centers of the Peyer's patches. The non-germinal centers of the Peyer's patch tissues showed delayed kinetics in B cell activation which occurred 10 days after infection. Quantification of the total number of B cells in these tissues was also carried out by staining the CD45RA marker on B cells with the OX33 monoclonal antibody. When comparing the total numbers of B cells with the numbers of B cells expressing dual isotypes of antibodies, our results showed the numbers of dual-expressing B cells (IgA:IgE, IgM:IgE, IgG1:IgE, IgG2a:IgE, IgG2b:IgE, and IgG2c:IgE), when combined, were over 7 times that of the total number of OX33-labeled B cells on day 7 in the small intestine. The dual-expressing B cells in the Peyer's patch-germinal center were more than 5 times that of the OX33-labeled B cells on day 15. These results therefore suggest that the dual-expressing B cells most likely synthesized and expressed more than two isotypes of antibodies during the peak days of the humoral response. Such phenomenon was not observed in non-germinal centers of the Peyer's patch tissues.

Encapsulating protein into preformed liposomes by ethanol-destabilized method.

This study describes a highly efficient method for encapsulating protein drugs into liposomes without using toxic solvents such as chloroform. Large unilamellar vesicles (LUVs) were formed by the ethanol injection method. The effects of composition of phospholipid, buffer concentration, incubation time, incubation temperature, drug loading, ethanol content, and the presence of poly(ethylene) glycol (PEG) lipids on the entrapment efficiency of protein were investigated. It was shown that these preformed LUVs could be induced to entrap protein drugs in the presence of ethanol. Protein could be efficiently encapsulated into liposomes. The interaction of the liposomes with proteins leads to the formation of multilamellar liposomes ranging in size from 70 to 120 nm, only slightly bigger than the parent LUVs from which they originated. Protein drugs were stable in the liposomal solution. There is no significant activity loss during the encapsulation process. The optimal encapsulation efficiency was achieved when 30% approximately 40% ethanol was used in encapsulating protein drugs. Due to the steric hindrance, LUVs containing a PEG coating will dramatically reduce the encapsulation efficiency, even in liposomes containing very low amount of PEG.