We present experimental and numerical results of current-driven magnetization switching in magnetic tunnel junctions. The experiments show that, for MgObased magnetic tunnelling junctions, the tunnelling magnetoresistance ratio is as large as 155% and the intrinsic switching current density is as low as 1.1 × 10 6 A cm −2. The thermal effect and current pulse width on spin-transfer magnetization switching are explored based on the analytical and numerical calculations. Three distinct switching modes, thermal activation, dynamic reversal, and precessional process, are identified within the experimental parameter space. The switching current distribution, write error, and read disturb are discussed based on device design considerations. The challenges and requirements for the successful application of spin-transfer torque as the write scheme in random access memory are addressed.

Spin-transfer torque magnetic random access memory (STT-MRAM) is a novel, magnetic memory technology that leverages the base platform established by an existing 100+nm node memory product called MRAM to enable a scalable nonvolatile memory solution for advanced process nodes. STT-MRAM features fast read and write times, small cell sizes of 6F 2 and potentially even smaller, and compatibility with existing DRAM and SRAM architecture with relatively small associated cost added. STT-MRAM is essentially a magnetic multilayer resistive element cell that is fabricated as an additional metal layer on top of conventional CMOS access transistors. In this review we give an overview of the existing STT-MRAM technologies currently in research and development across the world, as well as some specific discussion of results obtained at Grandis and with our foundry partners. We will show that in-plane STT-MRAM technology, particularly the DMTJ design, is a mature technology that meets all conventional requirements for an STT-MRAM cell to be a nonvolatile solution matching DRAM and/or SRAM drive circuitry. Exciting recent developments in perpendicular STT-MRAM also indicate that this type of STT-MRAM technology may reach maturity faster than expected, allowing even smaller cell size and product introduction at smaller nodes.

Objectives-The goals of this study were to determine the role of OCT3 in the pharmacologic action of metformin and to identify and functionally characterize genetic variants of OCT3 with respect to the uptake of metformin and monoamines.Methods-For the pharmacologic studies, we evaluated metformin-induced activation of AMPK, a molecular target of metformin. We used quantitative PCR and immunostaining to localize the transporter and isotopic uptake studies in cells transfected with OCT3 and its nonsynonymous genetic variants for functional analyses.Results-Quantitative PCR and immunostaining showed that OCT3 was expressed high on the plasma membrane of skeletal muscle and liver, target tissues for metformin action. Both the OCT inhibitor, cimetidine, and OCT3-specific shRNA significantly reduced the activating effect of metformin on AMPK. To identify genetic variants in OCT3, we used recent data from the 1000 Genomes Project and the Pharmacogenomics of Membrane Transporters project. Six novel missense variants were identified. In functional assays, using various monoamines and metformin, 3 variants, T44M (c.131C>T), T400I (c.1199C>T) and V423F (c.1267G>T), showed altered substrate specificity. Notably, in cells expressing T400I and V423F, the uptakes of metformin and catecholamines were significantly reduced but the uptakes of metformin, MPP+ and histamine by T44M were significantly increased more than 50%. Structural modeling suggested that these two variants may be located in the pore-lining (T400) or proximal (V423) membrane-spanning helixes.Conclusion-Our study suggests that OCT3 plays a role in the therapeutic action of metformin and that genetic variants of OCT3 may modulate metformin and catecholamine action.

Organic cation transporter 1 (OCT1; SLC22A1) seems to play a role in the efficacy and disposition of the widely used antidiabetic drug metformin. Genetic variants in OCT1 have been identified largely in European populations. Metformin is increasingly being used in Asian populations where the incidence of type 2 diabetes (T2D) is on the rise. The goal of this study is to identify genetic variants of OCT1 in Chinese and Japanese populations, which may potentially modulate response to metformin. We used recent data from the 1000 Genomes Project (Chinese and Japanese) and direct sequencing of selected amplicons of OCT1 in 66 DNA samples from Japanese patients with T2D. A total of six nonsynonymous variants were identified. Three of them (Q97K, P117L, and R206C) had not been functionally characterized previously and had allele frequencies of 0.017, 0.023 and 0.008, respectively. The uptake of metformin in cells expressing Q97K, P117L, and R206C was significantly reduced relative to the OCT1 reference (62 Ϯ 4.3, 55 Ϯ 6.8, and 22 Ϯ 1.5% for Q97K, P117L, and R206C, respectively). Kinetic studies indicated that P117L and R206C exhibited a reduced V max , whereas Q97K showed an increased K m . The green fluorescent protein (GFP)-tagged Q97K and P117L variants localized to the plasma membrane, whereas the GFP-tagged R206C was retained mainly in the endoplasmic reticulum. Replacement of the highly conserved R206 with different amino acids modulated the subcellular localization and function of the transporter. This study suggests that nonsynonymous variants of OCT1 in Chinese and Japanese populations may affect the differential response to metformin.

Dual magnetic tunnel junction (MTJ) structures consisting of two MgO insulating barriers of different resistances, two pinned reference layers aligned antiparallel to one another, and a free layer embedded between the two insulating barriers have been developed. The electron transport and spin dependent resistances in the dual MTJ structures are accounted for by sequential tunneling with some spin-flip relaxation in the central electrode (the free layer). With a tunneling magnetoresistance ratio of 70%, a switching current density Jc (at 30ms) of 0.52MA∕cm2 is obtained, corresponding to an intrinsic value of Jc0 (at 1ns) of 1.0MA∕cm2. This value of Jc0 is 2–3 times smaller than that of a single MgO insulating barrier MTJ structure and results from improvements in the spin-transfer torque efficiency. The asymmetry between JcAP→P and JcP→AP is significantly improved, which widens the read-write margin for memory device design. In addition, the experimental results show that the switching current density can be further reduced when an external field is applied along the hard axis of the free layer.