Full Particles Research Articles

Response Surface Optimisation of Polydimethylsiloxane (PDMS) on Borosilicate Glass and Stainless Steel (SS316) to Increase Hydrophobicity.

Particle deposition on the surface of a drying chamber is the main drawback in the spray drying process, reducing product recovery and affecting the quality of the product. In view of this, the potential application of chemical surface modification to produce a hydrophobic surface that reduces the powder adhesion (biofouling) on the wall of the drying chamber is investigated in this study. A hydrophobic polydimethylsiloxane (PDMS) solution was used in the vertical dipping method at room temperature to determine the optimum coating parameters on borosilicate glass and stainless steel substrates, which were used to mimic the wall surface of the drying chamber, to achieve highly hydrophobic surfaces. A single-factor experiment was used to define the range of the PDMS concentration and treatment duration using the Response Surface Methodology (RSM). The Central Composite Rotatable Design (CCRD) was used to study the effects of the concentration of the PDMS solution (X1, %) and the treatment duration (X2, h) on the contact angle of the substrates (°), which reflected the hydrophobicity of the surface. A three-dimensional response surface was constructed to examine the influence of the PDMS concentration and treatment duration on contact angle readings, which serve as an indicator of the surface’s hydrophobic characteristics. Based on the optimisation study, the PDMS coating for the borosilicate glass achieved an optimum contact angle of 99.33° through the combination of a PDMS concentration of X1 = 1% (w/v) and treatment time of X2 = 4.94 h, while the PDMS coating for the stainless steel substrate achieved an optimum contact angle of 98.31° with a PDMS concentration of X1 = 1% (w/v) and treatment time of X2 = 1 h. Additionally, the infrared spectra identified several new peaks that appeared on the PDMS-treated surfaces, which represented the presence of Si-O-Si, Si-CH3, CH2, and CH3 functional groups for the substrates coated with PDMS. Furthermore, the surface morphology analysis using the Field Emission Scanning Electron Microscopy (FESEM) showed the presence of significant roughness and a uniform nanostructure on the surface of the PDMS-treated substrates, which indicates the reduction in wettability and the potential effect of unwanted biofouling on the spray drying chamber. The application of PDMS and PTFE on the optimally coated substrates successfully reduced the amount of full cream milk particles that adhered to the surface. The low surface energy of the treated surface (19–27 mJ/m2) and the slightly higher surface tension of the full cream milk (54–59 mJ/m2) resulted in a high contact angle (102–103°) and reduced the adhesion work on the treated substrates (41–46 mJ/m2) as compared to the native substrates.

Do We Need to Consider Electrons' Kinetic Effects to Properly Model a Planetary Magnetosphere: The Case of Mercury

AbstractThe magnetosphere of Mercury is studied using an implicit full particle‐in‐cell simulation (PIC). We use a hybrid simulation where ions are full particles and electrons are considered as a fluid to start a PIC simulation where electrons are also particles and follow their distribution function. This approach allows us to estimate the changes introduced by the electron kinetic physics. We find that the overall macroscopic state of the magnetosphere of Mercury is little affected, but several physical processes are significantly modified in the full PIC simulation: the foreshock region is more active with more intense shock reformation, the Kelvin‐Helmholtz rippling effects on the nightside magnetopause are sharper, and the magnetotail current sheet becomes thinner than those predicted by the hybrid simulation. The greatest effect of the electron physics comes from the processes of particle energization. Both species, not just the electrons, are found to gain more energy when kinetic electron processes are included. The region with the most energetic plasma is found on the dusk side of the tail where magnetic flux ropes are formed due to reconnection. We find that the ion and electron energization is associated with the regions of reconnection and the development of kinetic instabilities caused by counter‐streaming electron populations. The resulting electron distributions are highly non Maxwellian, a process that neither MHD nor hybrid models can describe.

Human and Insect Cell-Produced Recombinant Adeno-Associated Viruses Show Differences in Genome Heterogeneity.

In the past two decades, adeno-associated virus (AAV) vector manufacturing has made remarkable advancements to meet large-scale production demands for preclinical and clinical trials. In addition, AAV vectors have been extensively studied for their safety and efficacy. In particular, the presence of empty AAV capsids and particles containing "inaccurate" vector genomes in preparations has been a subject of concern. Several methods exist to separate empty capsids from full particles; but thus far, no single technique can produce vectors that are free of empty or partial (non-unit length) capsids. Unfortunately, the exact genome compositions of full, intermediate, and empty capsids remain largely unknown. In this work, we used AAV-genome population sequencing to explore the compositions of DNase-resistant, encapsidated vector genomes produced by two common production pipelines: plasmid transfection in human embryonic kidney cells (pTx/HEK293) and baculovirus expression vectors in Spodoptera frugiperda insect cells (rBV/Sf9). Intriguingly, our results show that vectors originating from the same construct design that were manufactured by the rBV/Sf9 system produced a higher degree of truncated and unresolved species than those generated by pTx/HEK293 production. We also demonstrate that empty particles purified by cesium chloride gradient ultracentrifugation are not truly empty but are instead packaged with genomes composed of a single truncated and/or unresolved inverted terminal repeat (ITR). Our data suggest that the frequency of these "mutated" ITRs correlates with the abundance of inaccurate genomes in all fractions. These surprising findings shed new light on vector efficacy, safety, and how clinical vectors should be quantified and evaluated.

Ослабление диполь-дипольного взаимодействия в ансамблях микросфер кобальта с немагнитным ядром

Magnetic microspheres with nonmagnetic acrylic glass core were fabricated using electroless deposition. There are favorable conditions for magnetic flux closure within each particle. As a result, the dipole-dipole interaction in the powder of such microspheres is reduced drastically. This is the key difference between powders of magnetic microspheres and powders of full magnetic spherical particles witch behavior is significantly affected by the dipole-dipole interaction. The magnetic hysteresis in the cobalt microspheres with nonmagnetic core is significantly large then in the full cobalt particles produced using the same technique.

Dipole-dipole interaction weakening in ensembles of cobalt microspheres with a nonmagnetic core

Magnetic microspheres with nonmagnetic acrylic glass core were fabricated using electroless deposition. There are favorable conditions for magnetic flux closure within each particle. As a result, the dipole-dipole interaction in the powder of such microspheres is reduced drastically. This is the key difference between powders of magnetic microspheres and powders of full magnetic spherical particles witch behavior is significantly affected by the dipole-dipole interaction. The magnetic hysteresis in the cobalt microspheres with nonmagnetic core is significantly large then in the full cobalt particles produced using the same technique. Keywords: Magnetic microspheres, magnetic dipole-dipole interaction.

Novel anion exchange membrane chromatography method for the separation of empty and full adeno-associated virus.

A challenge in the production of recombinant Adeno-Associated Virus (AAV) for gene therapies is the presence of capsids that lack the required gene of interest. The impact of these empty vectors in therapies is not fully understood, however the ability to control the ratio of empty to full particles, which contain the genetic payload, is a necessary step in the purification of these viruses. In this study, a novel anion exchange chromatography elution method for enrichment of full AAV particles is demonstrated. A step gradient with small conductivity increases of around 1 mS cm-1 provides more efficient separation of empty and full AAV serotype 5 across membrane media as compared to conventional linear gradient method. The use of this approach in optimizing a simpler method for manufacturing processes and scalability to a larger chromatographic volume is explored. With this approach, the authors achieved greater than 4-fold enrichment of full capsids, to give a total of ≈50%-60% full capsids, using a 25mM Bis-Tris Propane pH 9.0 buffer system with NaCl as the eluting salt. Results suggest that this elution method can be implemented into a scalable process and can provide insight into development of elution methods for other AAV serotypes.

Comprehensive Size Distribution and Composition Analysis of Adeno-Associated Virus Vector by Multiwavelength Sedimentation Velocity Analytical Ultracentrifugation.

During the manufacturing of recombinant adeno-associated virus vectors, it is generally difficult to purify out vectors that lack nucleic acids (empty particles, EPs), contain incomplete nucleic acids (intermediate particles, IPs) or aggregates. These impurities may cause side effects and therefore it is essential to both quantify and reduce them; however, comprehensive identification of the size distribution and components of virus vectors have been lagging. We developed multiwavelength sedimentation velocity analytical ultracentrifugation to characterize EPs, full particles, IPs, and aggregates in adeno-associated virus vector samples. The wavelength-dependent ultraviolet (UV) absorption of capsid protein and encapsulated single-stranded DNA could be deduced from the multiwavelength detection followed by size distribution analysis and peak area integration. Subsequently, a spectral deconvolution analysis using the wavelength-dependent UV absorption data enabled the identification of the protein-nucleic acid ratio of all species. A comprehensive approach for quantifying the viral vector particles and related impurities was established.

Scalable downstream process development for in vivo gene therapy products: understanding full/empty separation capabilities and challenges with ion exchange chromatography

Adeno-associated viruses (AAVs) for in vivo gene therapy are a dominant viral vector platform in the gene therapy landscape. A key challenge in viral vector manufacturing, particularly with AAVs, is effective and consistent separation of full particles (i.e. viral vector capsids containing the full recombinant cDNA of the gene of interest) from empty capsids. Monolith-based ion exchange chromatography (IEX) is a promising tool to achieve this separation but poses challenges with consistency upon scale-up. This paper outlines some of the scale-up challenges and potential mitigations to achieve consistent separation of full and empty particles. IEX is evolving to become the industry standard for downstream separations as industrialization of gene therapy manufacturing continues.

A Native Mass Spectrometry-Based Assay for Rapid Assessment of the Empty:Full Capsid Ratio in Adeno-Associated Virus Gene Therapy Products.

Adeno-associated virus (AAV)-based gene therapy is a rapidly developing field, requiring analytical methods for detailed product characterization. One important quality attribute of AAV products that requires monitoring is the amount of residual empty capsids following downstream processing. Traditionally, empty and full particles are quantified via analytical ultracentrifugation as well as anion exchange chromatography using ultraviolet or fluorescence detection. Here, we present a native mass spectrometry-based approach to assess the ratio of empty to full AAV-capsids without the need for excessive sample preparation. We report the rapid determination of the relative amount of empty capsids in AAV5 and AAV8 samples. The results correlate well with more conventional analysis strategies, demonstrating the potential of native mass spectrometry for the characterization of viral particles.

Structural changes in bacteriophage T7 upon receptor-induced genome ejection

Many tailed bacteriophages assemble ejection proteins and a portal-tail complex at a unique vertex of the capsid. The ejection proteins form a transenvelope channel extending the portal-tail channel for the delivery of genomic DNA in cell infection. Here, we report the structure of the mature bacteriophage T7, including the ejection proteins, as well as the structures of the full and empty T7 particles in complex with their cell receptor lipopolysaccharide. Our near-atomic-resolution reconstruction shows that the ejection proteins in the mature T7 assemble into a core, which comprises a fourfold gene product 16 (gp16) ring, an eightfold gp15 ring, and a putative eightfold gp14 ring. The gp15 and gp16 are mainly composed of helix bundles, and gp16 harbors a lytic transglycosylase domain for degrading the bacterial peptidoglycan layer. When interacting with the lipopolysaccharide, the T7 tail nozzle opens. Six copies of gp14 anchor to the tail nozzle, extending the nozzle across the lipopolysaccharide lipid bilayer. The structures of gp15 and gp16 in the mature T7 suggest that they should undergo remarkable conformational changes to form the transenvelope channel. Hydrophobic α-helices were observed in gp16 but not in gp15, suggesting that gp15 forms the channel in the hydrophilic periplasm and gp16 forms the channel in the cytoplasmic membrane.

Comparison of Different Liquid Chromatography-Based Purification Strategies for Adeno-Associated Virus Vectors.

Recombinant adeno-associated virus (rAAV) vectors have evolved as one of the most promising technologies for gene therapy due to their good safety profile, high transduction efficacy, and long-term gene expression in nondividing cells. rAAV-based gene therapy holds great promise for treating genetic disorders like inherited blindness, muscular atrophy, or bleeding disorders. There is a high demand for efficient and scalable production and purification methods for rAAVs. This is particularly true for the downstream purification methods. The current standard methods are based on multiple steps of gradient ultracentrifugation, which allow for the purification and enrichment of full rAAV particles, but the scale up of this method is challenging. Here, we explored fast, scalable, and universal liquid chromatography-based strategies for the purification of rAAVs. In contrast to the hydrophobic interaction chromatography (HIC), where a substantial amount of AAV was lost, the cation exchange chromatography (CEX) was performed robustly for multiple tested serotypes and resulted in a mixture of full and empty rAAVs with a good purity profile. For the used affinity chromatography (AC), a serotype dependence was observed. Anion exchange chromatography (AEX) worked well for the AAV8 serotype and achieved high levels of purification and a baseline separation of full and empty rAAVs. Depending on the AAV serotype, a combination of CEX and AEX or AC and AEX is recommended and holds promise for future translational projects that require highly pure and full particle-enriched rAAVs.

Analytical band centrifugation for the separation and quantification of empty and full AAV particles

Analytical band centrifugation (ABC) was first developed for the separation of macromolecules in centrifugation cells ~60 years ago. Since its development, ABC has been predominantly utilized to study macromolecular interactions or chemical reactions between two solutions in situ upon mixing. In this current study, we evaluated ABC separations on modern analytical ultracentrifugation (AUC) instruments for therapeutic adeno-associated viruses (AAVs). ABC provided sufficient separation between the genome-containing full AAV particle and the empty AAV capsid, which need to be controlled during the manufacturing process. Because ABC produces a physical separation, no complex algorithm or sophisticated software is needed to process the experimental raw data. ABC profiles, dubbed “centrifugrams”, can be analyzed with a similar approach as typically used for electrophoretic separations to produce relative percent area. Sedimentation coefficients (s) of analytes can also be determined from ABC. The relative area percent and s value obtained in ABC experiments were shown to be consistent with those determined by conventional sedimentation velocity AUC (SV-AUC). Additionally, the separation and quantification by ABC were found to be reproducible and did not appear to be sensitive to experimental variations of initial rotor temperature or cell misalignment. The robustness of the separation, ease of data processing, and universal applicability for analysis of different AAV serotypes make ABC a promising technique for routine analysis of empty and full AAV particle composition in therapeutic products.

Characterization of Recombinant Adeno-Associated Viruses (rAAVs) for Gene Therapy Using Orthogonal Techniques.

Viruses are increasingly used as vectors for delivery of genetic material for gene therapy and vaccine applications. Recombinant adeno-associated viruses (rAAVs) are a class of viral vector that is being investigated intensively in the development of gene therapies. To develop efficient rAAV therapies produced through controlled and economical manufacturing processes, multiple challenges need to be addressed starting from viral capsid design through identification of optimal process and formulation conditions to comprehensive quality control. Addressing these challenges requires fit-for-purpose analytics for extensive characterization of rAAV samples including measurements of capsid or particle titer, percentage of full rAAV particles, particle size, aggregate formation, thermal stability, genome release, and capsid charge, all of which may impact critical quality attributes of the final product. Importantly, there is a need for rapid analytical solutions not relying on the use of dedicated reagents and costly reference standards. In this study, we evaluate the capabilities of dynamic light scattering, multiangle dynamic light scattering, and SEC–MALS for analyses of rAAV5 samples in a broad range of viral concentrations (titers) at different levels of genome loading, sample heterogeneity, and sample conditions. The study shows that DLS and MADLS® can be used to determine the size of full and empty rAAV5 (27 ± 0.3 and 33 ± 0.4 nm, respectively). A linear range for rAAV5 size and titer determination with MADLS was established to be 4.4 × 1011–8.7 × 1013 cp/mL for the nominally full rAAV5 samples and 3.4 × 1011–7 × 1013 cp/mL for the nominally empty rAAV5 samples with 3–8% and 10–37% CV for the full and empty rAAV5 samples, respectively. The structural stability and viral load release were also inferred from a combination of DLS, SEC–MALS, and DSC. The structural characteristics of the rAAV5 start to change from 40 °C onward, with increasing aggregation observed. With this study, we explored and demonstrated the applicability and value of orthogonal and complementary label-free technologies for enhanced serotype-independent characterization of key properties and stability profiles of rAAV5 samples.

Efficacy of Coxsackievirus A5 Vaccine Candidates in an Actively Immunized Mouse Model.

Coxsackievirus A5 (CV-A5) has recently emerged as a main hand, foot, and mouth disease (HFMD) pathogen. Following a large-scale vaccination campaign against enterovirus 71 (EV-71) in China, the number of HFMD-associated cases with EV-71 was reduced, especially severe and fatal cases. However, the total number of HFMD cases remains high, as HFMD is also caused by other enterovirus serotypes. A multivalent HFMD vaccine containing 4 or 6 antigens of enterovirus serotypes is urgently needed. A formaldehyde-inactivated CV-A5 vaccine derived from Vero cells was used to inoculate newborn Kunming mice on days 3 and 10. The mice were challenged on day 14 with a mouse-adapted CV-A5 strain at a dose that was lethal for 14-day-old suckling mice. Within 14 days postchallenge, groups of mice immunized with three formulations, empty particles (EPs), full particles (FPs), and a mixture of the EP and FP vaccine candidates, all survived, while 100% of the mock-immunized mice died. Neutralizing antibodies (NtAbs) were detected in the sera of immunized mice, and the NtAb levels were correlated with the survival rate of the challenged mice. The virus loads in organs were reduced, and pathological changes and viral protein expression were weak or not observed in the immunized mice compared with those in alum-inoculated control mice. Another interesting finding was the identification of CV-A5 dense particles (DPs), facilitating morphogenesis study. These results demonstrated that the Vero cell-adapted CV-A5 strain is a promising vaccine candidate and could be used as a multivalent HFMD vaccine component in the future.IMPORTANCE The vaccine candidate strain CV-A5 was produced with a high infectivity titer and a high viral particle yield. Three particle forms, empty particles (EPs), full particles (FPs), and dense particles (DPs), were obtained and characterized after purification. The immunogenicities of EP, FP, and the EP and FP mixture were evaluated in mice. Mouse-adapted CV-A5 was generated as a challenge strain to infect 14-day-old mice. An active immunization challenge mouse model was established to evaluate the efficacy of the inactivated vaccine candidate. This animal model mimics vaccination, similar to immune responses of the vaccinated. The animal model also tests protective efficacy in response to the vaccine against the disease. This work is important for the preparation of multivalent vaccines against HFMD caused by different emerging strains.

Separating Empty and Full Recombinant Adeno-Associated Virus Particles Using Isocratic Anion Exchange Chromatography.

The development of recombinant adeno-associated virus (rAAV) gene therapies is becoming an increasing priority in the biotherapeutic landscape. One of the challenges associated with the production of rAAV is the formation of empty AAV particles that do not contain a therapeutic gene. The concerns about the impact of empty particles on clinical safety and rAAV-mediated gene expression have necessitated the development of purification processes to remove these species. The development of a robust and scalable purification process to separate empty and full AAV particles at large scale remains a challenge. In this study, a novel anion exchange chromatography process based on isocratic wash and elution steps to enrich full rAAV2 particles is presented. An operating design space is identified to ensure the robustness of the process. The isocratic chromatography provides several advantages over the traditional shallow linear gradient elution, including lower buffer consumption, smaller intermediate pool volumes, and more robust manufacturing.

The use of capillary electrophoresis in Gene Therapy

Background & Aim Capillary Electrophoresis (CE) has undergone a huge resurgence over the last 15 years as the pharmaceutical industry moved from traditional small molecule pharmaceuticals into more complex biologicals and protein and peptide-based biopharmaceuticals. Today there is a drive to look for more target approaches to treat rare diseases and one of the areas which is seeing a rapid increase in funding is the development of gene therapy-based products. Gene therapy products often use a viral vector (capsid) as a carrier to transfer DNA/RNA to cells and these products provide an additional level of complexity over antibodies so profiling and analysing such products has thrown up new challenges for analytical chemists. In this work we will present how CE has been used to profile and analytical test new Gene Therapy products. The methods takes advantage of the traditional approaches of CE used in monoclonal antibody testing and adapts them to analysing the building blocks of the gene therapy product as well as the final product itself. Methods, Results & Conclusion The methods used are based on CE-SDS protein assays or capillary isoelectric profiling methods (cIEF) using commercially available capillaries and consumables. In the analysis of viral proteins which make up the adeno associated virus (AAV) vectors a new protein derivatisation step has now been developed to fluorescently tag the proteins in a simple 2 step process to enhance the sensitivity and detect viral capsid proteins. The sensitivity improvement is required due to the lower protein concentrations found in gene therapy products. The CE-SDS method developed using this new flourescent tag has allowed AAV viral proteins to be detected at a viral particle concentration of 1.1 × 10 10 GC/ml and is very reproducible. In a new application using cIEF we will show how CE is now able to profile empty vs full AAV gene therapy products and is capabale of being applied to several different serotypes. In conclusion CE can now be used in the analysis of gene therapy products and can not only profile the proteins making up the viral vectors but can also be used to profile the AAV final products to provide information on empty versus full particles.

Three-dimensional particle shape characterizations from half particle geometries

Many three-dimensional (3D) imaging techniques, such as 3D laser scanner, stereophotography, and structured light techniques, can only capture upper half particle geometries in the camera view, and lower half particle geometries are occluded from the camera. This research aims to evaluate the accuracy of using half particle geometries to compute 3D particle shape descriptors. Computational geometry techniques are developed to compute eight commonly used particle shape descriptors automatically. Five coarse sand specimens are scanned by X-ray computed tomography and structured light to generate full 3D and half particle geometries, respectively. The convexity, diameter sphericity, and surface area sphericity computed from half particles overestimate these values computed from full 3D particles, which are corrected by statistical equations. The circularity, volume sphericity, intercept sphericity, sphere ratio sphericity, and roundness computed from half particles agreed excellently with these values computed from 3D particles.

Fluorescence labelling and self-healing microcapsules for detection and repair of surface microcracks in cement matrix

Fluorescence labelling and self-healing microcapsules (FLSM) with fluorescein sodium labelled epoxy resin as core materials and urea-formaldehyde resin as shell materials were synthesized by in situ polymerization via ultrasonic dispersion. Micromorphology, chemical structure, thermal stability and reactivity of FLSM were studied by ESEM, FTIR, TGA and DSC. Laser scanning confocal microscopy (LSCM) was served to characterize the surface microcracks repair process of cement paste mixed FLSM. The results showed that FLSM with full spherical particles and a certain roughness on the surface were well dispersed in the range of 150–300 μm of particle size. The addition of fluorescein sodium has no significant effect on the micromorphology, chemical structure, thermal stability and reactivity of FLSM. After being cut by the blade, the fluorescence width of FLSM increased from 9 μm to 22 μm within 0–12 h. The core materials of FLSM was basically lost, which indicated that the core materials had good fluidity. When the microcracks occur on the surface of cement paste, FLSM can not only detect the specific location of the microcracks and repair them, but also infer the width of the microcracks. It provides a new method for detecting and repairing microcracks on the surface of cement matrix.

TPP Combined with DGUC as an Economic and Universal Process for Large-Scale Purification of AAV Vectors

Adeno-associated virus (AAV) vectors have been commonly purified through density gradient ultracentrifugation (DGUC) or column chromatography methods. Although the DGUC method can efficiently separate the empty from the full virus particles, its application in large-scale AAV purification is hindered due to its limitation in volume of each centrifuge tube. Alternatively, column chromatography is serotype-dependent, expensive, and complicated, which co-purifies both empty and full virus particles. In this study, we describe an economical and universal process using three-phase partitioning (TPP) combined with DGUC to purify large quantities of AAV vectors. First, TPP is used to remove up to 90% of the cellular impurities in the cell lysate and at the same time condense the AAV vectors into ∼10% of their original lysate volume. Second, two rounds of DGUC are employed to separate the empty from the full virus particles and at the same time remove the remaining cellular impurities. This combined process increases the capacity of ultracentrifugation by a factor of 5- to 10-fold depending on the yields of AAV serotypes. A variety of AAV serotypes such as AAV2, AAV5, AAV6, AAV9, and AAVDJ have been successfully purified with this process. Both in vitro and in vivo studies demonstrate that TPP has no detrimental impact on AAV infectivity. In a proof of concept, we performed several purification runs ranging from 3 to 25 L of Sf9 culture volume. We were able to purify more than 3e+15 viral genomes (vg) of AAV vectors from 3 L of cell culture volume with just two SW28 centrifuge tubes in a Beckman Coulter ultracentrifuge. Our data indicate that this TPP-DGUC process is economic, universal, and can be used to purify a large quantity of AAV vectors for clinical applications with just a few ultracentrifuges.

A Novel Approach for Synthesis of Nickel-Rich Layered Oxide Cathode Materials with Tailored Morphology and Their Electrochemical Performance

The improvement in energy density of lithium ion batteries (LIBs) is primarily focused on the increase of the specific capacity of active materials and the cell voltage.[1] Transition metal (TM) oxide-based cathodes materials reach a high specific capacity through the optimization of the chemical composition with a higher Ni content and can be cycled up to 4.6 V.[2] However, the electrochemical performance of Ni-rich cathode materials depends strongly on their physical properties such as particle size, specific surface area or surface characteristics. The poor rate capability and capacity retention as well as the high first cycle irreversible capacity loss (ICL) and the low volumetric energy density of electrodes have to be improved by specific design of the particle shape. A spherical morphology with a narrow size distribution is the preferred particle shape and can only be synthesized during the co-precipitation of TM-hydroxides or -carbonates by a continuously stirred tank reactor (CSTR). Additionally, the CSTR-process allows a further improvement of the cathode materials during the synthesis of core-shell and full concentration-gradient particles.[2] In this work, the design and the operating principle of a novel Couette-Taylor-Flow-Reactor (CTFR) is evaluated regarding the synthesis of spherical shaped Ni-rich TM-precursors. The CTFR offers a continuous process and is constructed by two co‐axial arranged cylinders with a small gap and a low working volume. The rotational motion of the inner cylinder induces a turbulent Taylor‐vortex flow. Above the suitable Taylor number (Ta), a periodic and stable turbulent fluid motion is formed, which increases the fluid shear and the local concentration of educts and promotes the agglomeration of precipitates to uniform spherical particles with narrow particle size distribution.[3] Based on the co-precipitation of Ni-rich TM-precursors by a continuous CTFR, the influence of the reaction conditions on the properties of TM-precursor is investigated. The rotational speed, residence time, temperature and pH-value were varied in a broad range. The growth behavior of the particles, regarding the morphology, particle size distribution, tap density and chemical composition of TM-precursors as well as for lithiated cathode materials are investigated. The electrochemical properties of the corresponding cathode materials with their unique particle morphology in dependence of the co-precipitation conditions are comprehensively evaluated for finding the optimal synthesis conditions. [1] J. Betz, G. Bieker, P. Meister, T. Placke, M. Winter, R. Schmuch, Adv. Energy Mater. 2018, 1803170/1-18.[2] H. Li, P. Zhou, F. Liu, H. Li F. Cheng, J. Chen, Chem. Sci, DOI: 10.1039/c8sc03385d.[3] J.-M. Kim, S.-M. Chang, J.-H. Chang, W.-S- Kim, Colloids and Surfaces A: Physicochem. Eng. Aspects (2011) 384, 31-39.