From N-1 to purified product in a closed and connected single use technology process industry

Improvements in biopharmaceutical productivity and flexibility are achieved when unit operations in the production train perform in concert with each other. Achieving smooth interactions between unit operations requires combining single-use technology, hardware, automation, process design, and in-line process control. Connected manufacturing refers to both physical and digital connections throughout the process of seamlessly linked unit operations through compatible physical connections. Each unit operation can be ready to anticipate and respond to fluctuations in process conditions leading to the ability to operate for the long processing times present in continuous processes. Preferably, connected manufacturing integrates an overarching layer of automation across multiple steps in the bioprocess train extending from upstream to downstream. Aligned with the physical connections, digital connections coordinate the individual unit operations with each other and minimize manual operations requiring operator intervention. Unit level automation and process level integration are critical to successful connected manufacturing. Closed processes reduce the risk of contamination which can be magnified during the long processing times of continuous operations. Single-use technology is both an enabler and the preferred platform for closed process steps, especially the steps before viral inactivation. This presentation describes the concepts of connecting a continuous upstream perfusion process to a closed and connected downstream process. In addition, two single-use compatible technologies were evaluated for the Protein A capture step: traditional columns in a pre-packed format and filter based adsorbers. We will show results from this closed and connected process starting at the N-1 step going all the way to the purified product. The results provide useful insights for biomanufacturers who are considering the value of connected processes. Furthermore, we will give insights about process design considerations, risks analysis, resource planning, buffer management and process automation

Efficient approaches for perfusion medium development

Here, we present a fast and convenient strategy for developing a high-cell density perfusion process for antibody-producing Chinese hamster ovary (CHO) cells based on the commercially available ActiCHO™ Media System. ActiCHO P base medium was used as a starting point and ActiCHO Feed-A and Feed-B were added in various concentrations as supplements. The resulting perfusion medium prototypes were first evaluated in batch cultures, applying a design of experiment (DoE) strategy (Figure 1), and then tested in small-scale perfusion cultures in rocking single-use WAVE bioreactor™ systems (Figure 2). The medium optimization resulted in a final process with a cell-specific perfusion rate (CSPR) of less than 50 pL/cell/d, which is a more than 45% decrease compared with the starting process conditions. The performance of the perfusion process was further validated in lab-scale single-use stirred-tank bioreactor systems. Productivity and product quality of the perfusion process were compared with a standard fed-batch culture process

Silicon oxide-niobium oxide mixture films and nanolaminates grown by atomic layer deposition from niobium pentaethoxide and hexakis(ethylamino) disilane

Amorphous SiO2-Nb2O5 nanolaminates and mixture films were grown by atomic layer deposition. The films were grown at 300 degrees C from Nb(OC2H5)(5), Si-2(NHC2H5)(6), and O-3 to thicknesses ranging from 13 to 130 nm. The niobium to silicon atomic ratio was varied in the range of 0.11-7.20. After optimizing the composition, resistive switching properties could be observed in the form of characteristic current-voltage behavior. Switching parameters in the conventional regime were well defined only in a SiO2:Nb2O5 mixture at certain, optimized, composition with Nb:Si atomic ratio of 0.13, whereas low-reading voltage measurements allowed recording memory effects in a wider composition range.Peer reviewe

A construção do Jornal do Centro de Atenção Psicossocial II: desenvolvendo habilidades específicas e relacionais

Objective: to demonstrate the possibilities of a multidisciplinary workshop on developing hard and soft skills to improve rehabilitation. Methods: experience’s description of conducting a working group aimed to writing and editing a newspaper. Through such specific task, different hard and soft skills are developed. Hard skills are specific abilities, such as using the computer and the internet, whereas soft skills are social skills, such as how to relate to others and negotiate. Results: empowerment of the clients by enhancing abilities with tools like the computer and the internet; Development of relational capacities, such leadership and group working. Final considerations: this multidisciplinary therapeutic workshop is useful to enhance clients’ work and social skills and improve their rehabilitation process

Electric and Magnetic Properties of Atomic Layer Deposited ZrO2-HfO2 Thin Films

Atomic layer deposition method was employed to deposit thin films consisting of ZrO2 and HfO2. Zirconia films were doped with hafnia and vice versa, and also nanolaminates were formed. All depositions were carried out at 300 degrees C. Most films were crystalline in their as-deposited state. Zirconia exhibited the metastable cubic and tetragonal phases by a large majority, whereas hafnia was mostly in its stable monoclinic phase. Magnetic and electrical properties of the films were assessed. Un-doped zirconia was ferromagnetic and this property diminished with increasing the amount of hafnia in a film. All films exhibited ferroelectric-like behavior and the polarization curves also changed with respect to the film composition. (C) The Author(s) 2018. Published by ECS.Peer reviewe

Properties of Atomic Layer Deposited Nanolaminates of Zirconium and Cobalt Oxides

Five-layer crystalline thin film structures were formed, consisting of ZrO2 and Co3O4 alternately grown on Si(100) substrates by atomic layer deposition at 300 degrees C using ZrCl4 and Co(acac)(3) as the metal precursors and ozone as the oxygen precursor. The performance of the laminate films was dependent on the relative content of constituent oxide layers. The magnetization in these films was nonlinear, saturative, and with very weak coercive fields. Electrical measurements revealed the formation of significant polarization versus external field loops and implied some tendency toward memristive behavior. (C) The Author(s) 2018. Published by ECS.Peer reviewe

Magnetic and Electrical Performance of Atomic Layer Deposited Iron Erbium Oxide Thin Films

Mixed films of a high-permittivity oxide, Er2O3, and a magnetic material, Fe2O3, were grown by atomic layer deposition on silicon and titanium nitride at 375 degrees C using erbium diketonate, ferrocene, and ozone as precursors. Crystalline phases of erbium and iron oxides were formed. Growth into three-dimensional trenched structures was demonstrated. A structure deposited using tens to hundreds subsequent cycles for both constituent metal oxide layers promoted both charge polarization and saturative magnetization compared to those in the more homogeneously mixed films.Peer reviewe

Atomic Layer Deposition and Performance of ZrO2-Al2O3 Thin Films

Thin mixed and nanolaminate films of ZrO2 and Al2O3 were grown by atomic layer deposition from the corresponding metal chlorides and water. The films were grown at 350 degrees C in order to ensure ZrO2 crystallization in the as-deposited state. The relative thicknesses of layers in the structure of the nanolaminates were controlled in order to maximize the content of metastable polymorphs of ZrO2 that have higher permittivity than that of the stable monoclinic ZrO2 . The multilayer films demonstrated interfacial charge polarization and saturative magnetization in external fields. The conductivity of the films could be switched between high and low resistance states by applying voltages of alternating polarity. (C) 2018 The Electrochemical Society.Peer reviewe

Magnetic properties and resistive switching in mixture films and nanolaminates consisting of iron and silicon oxides grown by atomic layer deposition

SiO2-Fe2O3 mixture films and nanolaminates were grown by atomic layer deposition from iron trichloride, hexakis(ethylamino)disilane, and ozone at 300 degrees C. Orthorhombic -Fe2O3 was identified in Fe2O3 reference films and in Fe2O3 layers grown to certain thicknesses between amorphous SiO2 layers. SiO2-Fe2O3 films could be magnetized in external fields, exhibiting saturation and hysteresis in nonlinear magnetization-field curves. Electrical resistive switching, markedly dependent on the ratio of the component oxides, was also observed in films with proper composition. For relatively conductive films, application of small signal measurements allowed one to record memory maps with notable squareness and defined distinction between high and low conductance states.Peer reviewe