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Progress in deep sub-micron scaling for logic and memoryAt the International Electron Devices Meeting in San Francisco imec's advanced CMOS research program reports promising advances in scaling logic, DRAM and non-volatile memory. A new device based on non-silicon channels was realized to scale high-performance logic towards the sub-20nm node. Moreover, imec developed low-leakage capacitors allowing DRAM to be pushed to the 2x nm node. And the switching mechanism of resistive RAM for next-generation flash memories (RRAM) has been unraveled.
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Assessment of the Injection Performance of a Tapered Needle for Use in Prefilled Biopharmaceutical ProductsThe design of injection devices, including prefilled syringes (PFSs) and autoinjectors, requires an understanding of the optimization of injection conditions. The injection of highly concentrated biopharmaceuticals can lead to exceptionally high injection forces, due to their high viscosity. To overcome this challenge, a tapered needle has been recently developed by Terumo Corporation. In the present study, we measured the injection forces in PFSs equipped with 24G-29G tapered needle (29G TNN), 27G thin-wall needle (27G TW), and 29G TW using several model and pharmaceutical protein solutions. The injection forces measured in the 29G TNN PFSs were lower than those in 29G TW for all solutions, similar to those in 27G TW PFSs for Newtonian solutions, and were lower than those in the 27G TW PFSs for non-Newtonian solutions which demonstrated shear-thinning behavior. No significant changes in aggregates or micron-size particle concentrations were observed upon injection, regardless of the needle type. Mathematical modeling supported the experimental findings that under similar flow rate conditions injection pressure in a tapered needle is lower than that in a cylindrical needle. Our results indicate that there are advantages of using tapered needles for the injection of biopharmaceutical formulations particularly those showing shear-thinning behavior.
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Development status of Terumo implantable left ventricular assist system.We have been developing an implantable left ventricular assist system (T‐ILVAS) featuring a magnetically suspended centrifugal pump (MSCP) since 1995. In vitro and in vivo studies using a prototype MSCP composed of a polycarbonate housing and impeller (196 ml) have demonstrated long‐term durability and excellent blood compatibility for up to 864 days, and excellent stability of the magnetic bearing of the MSCP. These preliminary results strongly suggested that the magnetic bearing of the MSCP is reliable and is a most feasible mechanism for a long‐term circulatory assist device. We have recently devised a clinical version pump made of titanium (180 ml) with a new position sensor mechanism and a wearable controller with batteries. Cadaver fit study confirmed that the Type IV pump could be implanted in a small patient with a body surface area as small as 1.3. The in vitro performance tests of the Type IV pump demonstrated excellent hydrodynamic performances with an acceptable hemolysis rate. New position sensors for the titanium housing showed more uniform sensor outputs of a magnetic bearing than in the prototype polycarbonate pump. The Type IV pump then was evaluated in vivo in 6 sheep at the Oxford Heart Centre. Four sheep were electively sacrificed at 3 months and were allowed to survive for more than 6 months for long‐term evaluation. In this particular series of experiments, no anticoagulant/antiplatelet regimen was utilized except for a bolus dose of heparin during surgery. There was a left ventricular mural thrombi around the inflow cannula in 1 sheep. Otherwise, there was no mechanical failure nor sign of thromboembolism throughout the study.
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A comparison of automated perfusion- and manual diffusion-based human regulatory T cell expansion using a soluble activator complexBackground & Aim Human regulatory T cells (hTregs) play a central role in the maintenance of self-tolerance and suppression of autoimmune responses. The absence or reduced frequency of hTregs can limit the control of immune inflammatory responses, autoimmunity and the success of transplant engraftment. Clinical studies indicate that the use of hTregs as immunotherapeutics would require billions of cells per dose; e.g., Phase I studies by Mathew et al (2018) suggest that hTreg doses in the range of 0.5 to 5.0 × 109 cells are needed to facilitate kidney transplantation and clinical studies by Bluestone et al (2015) indicate that polyclonal hTreg doses in the range of 5 × 106 to 2.6 × 109 cells are well tolerated in type 1 diabetes patients. The Quantum Cell Expansion System is a hollow-fiber (HFM) bioreactor system that has been used to grow billions of functional T-cells in a short timeframe (8 to 9 days). We have now focused our protocol development on the ex vivo expansion of selected hTregs in the Quantum system using a soluble activator, composed of an anti-CD3/CD28/CD2 tetrameric mAb complex. Methods, Results & Conclusion hTreg CD4+CD25+CD127− cells from 3 unrelated healthy donors, previously isolated by the vendor via column-free Imag positive selection, were thawed and grown under static conditions and subsequently seeded into Quantum system HFM bioreactors and into T225 control flasks in an identical culture volume of 124 mL PRIME-XV® XSFM medium supplemented with 100 IU/mL of rhIL-2 and antibiotics for scale-up expansion over 9 days to compare the effects of automated perfusion with manual diffusion-based culture. Cell growth, viability, and phenotype of the hTregs were compared. The hTreg cell harvest from 3 parallel expansion runs produced an average of 4.0 × 108 (range 1.9 to 5.6 × 108) hTregs in the flask arm with an average viability of 71.3% versus 7.0 × 109 (range 3.6 to 13.0 × 109) hTregs in the Quantum arm with an average viability of 91.8%. This translates into an average 17.7-fold increase in hTreg cell yield for the Quantum system over that obtained in flasks, coupled with a higher cell viability in the Quantum system. In addition, these 2 culture processes gave rise to cells with an hTreg CD4+CD25+FoxP3+ phenotype of 76.5% for the flask arm versus 80.3% for the Quantum system arm. The results suggest that an automated perfusion HFM bioreactor can support the scale-up expansion of hTreg cells more efficiently than diffusion-based flask culture.
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Randomized Comparison of Terumo® Coated Slender™ versus Terumo® Noncoated Traditional Sheath during Radial Angiography or Percutaneous Coronary InterventionBackground. The transradial approach is generally associated with few complications. However, periprocedural pain is still a common issue, potentially related to sheath insertion and/or arterial spasm, and may result in conversion to femoral access. Radial artery occlusion (RAO) following the procedure is also a potential risk. We evaluate whether the design of the sheath has any impact on these variables. Methods. A total of 1,000 patients scheduled for radial CAG or PCI were randomized (1:1) to the use of a Slender or a Standard sheath during the procedure. Randomization was stratified according to chosen sheath size (5, 6, 7 French) and gender. A radial band was used to obtain hemostasis after the procedure, employing a rapid deflation technique. A reverse Barbeau test was performed to evaluate radial artery patency after removal of the radial band, and level of pain was assessed using a numeric rating scale (NRS). Results. Use of the Slender sheath was associated with less pain during sheath insertion (median NRS 1 versus 2, p=0.02), whereas no difference was observed in pain during the procedure, radial procedural success rates, use of analgesics and sedatives during the procedure, and radial artery patency following the procedure. Rate of RAO was 1.5% with no difference between groups. Conclusion. The use of the hydrophilic coated Slender sheath during radial CAG or PCI was associated with less pain during sheath insertion, whereas no difference in other endpoints was observed. A rapid deflation technique was associated with RAO of only 1.5%.
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Silicon microring resonatorsAn overview is presented of the current state‐of‐the‐art in silicon nanophotonic ring resonators. Basic theory of ring resonators is discussed, and applied to the peculiarities of submicron silicon photonic wire waveguides: the small dimensions and tight bend radii, sensitivity to perturbations and the boundary conditions of the fabrication processes. Theory is compared to quantitative measurements. Finally, several of the more promising applications of silicon ring resonators are discussed: filters and optical delay lines, label‐free biosensors, and active rings for efficient modulators and even light sources.
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A Cautionary Note When Looking for a Truly Reconfigurable Resistive RAM PUFThe reconfigurable physically unclonable function (PUF) is an advanced security hardware primitive, suitable for applications requiring key renewal or similar refresh functions. The Oxygen vacancies-based resistive RAM (RRAM), has been claimed to be a physically reconfigurable PUF due to its intrinsic switching variability. This paper first analyzes and compares various previously published RRAM-based PUFs with a physics-based RRAM model. We next discuss their possible reconfigurability assuming an ideal configuration-to-configuration behavior. The RRAM-to-RRAM variability, which mainly originates from a variable number of unremovable vacancies inside the RRAM filament, however, has been observed to have significant impact on the reconfigurability. We show by quantitative analysis on the clear uniqueness degradation from the ideal situation in all the discussed implementations. Thus we conclude that true reconfigurability with RRAM PUFs might be unachievable due to this physical phenomena.
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Impact of calibrated band-tails on the subthreshold swing of pocketed TFETsThe tunnel field-effect transistor (TFET) is one of the prime steep-slope device candidates to be employed in future ultra-low power logic applications [1], [2], and can achieve sub-60 mV/dec subthreshold swings (SS) using quantum mechanical (QM) band-to-band tunneling (BTBT). One of the main challenges for TFETs is obtaining a sufficiently high drive-current ION [1]. The ION can be enhanced by introducing a highly-counter-doped pocket at the tunnel junction [3], [4]. However, it is well known that high doping concentrations introduce band-tails states in the bandgap [5]. First assessments on band-tails in TFETs, linked to diode measurements, have been made [6]–[8]. However, it is unknown whether the band-tails-induced tunneling contributions limit the performance of optimized pocketed TFETs. In this work, we investigate the impact of band-tails on the SS of p-n-i-n In0.53Ga0.47As and InAs TFETs for different pocket thicknesses and doping concentrations in the source and pocket, while using band-tails density-of-states (DOS) obtained from successful diode calibrations [8].