Development of High Performance Electrode of Lithium Ion Battery By High Speed Manufacturing Using Continuous Kneading Process

Active pharmaceutical ingredient (API) production involving continuous processes – A process system engineering (PSE)-assisted design framework

The continuous processing session at the 2023 Viral Clearance Symposium (VCS) focused on understanding how to effectively design viral clearance operations for use in continuous processes and methods to perform viral clearance studies. In this session, an approach to directly address control considerations with operating continuous-flow reactors for low pH viral inactivation was presented. Continuous-flow low pH incubation chamber design and implications for residence time determination were discussed. Additionally, viral clearance capability between batch operation and connected operation were demonstrated to be comparable for a connected bind-elute chromatography and flow-through chromatography step. Overall, this session provided additional scientific knowledge to support viral clearance strategies when implementing a continuous manufacturing process.

1. IntroductionAchieving higher capacity lithium-ion batteries requires a delicate balance between a high amount of active materials and a minimum amount of conductive additives within electrode slurries. These slurries, dispersed in a non-aqueous polymeric suspension, rely on homogeneous dispersibility of active materials and conductive additives[1]. However, challenges arise from the tendency of carbon black (average size <100 nm, falling under the colloidal regime) to aggregate, compromising battery efficiency. Achieving well-dispersed carbon conductive additives and a stable, well-connected three-dimensional percolated network structure within the slurry with a minimal amount of carbon additive is a significant challenge. To address this challenge, our research focuses on optimizing the carbon percolation network within electrode slurries utilizing the fundamentals of electrochemical impedance spectroscopy (EIS). Our aim is to evaluate particle dispersibility within the slurry, providing valuable insights into structural changes under both steady-state and applied shear forces (various flow conditions). This innovative approach offers a promising avenue for streamlining manufacturing processes and advancing lithium-ion battery technology towards greater efficiency and performance. EIS enables detailed analysis of resistance/constant phase elements (CPE) values based on differences in the frequency response of the electric double layer, offering insight into various sizes of particle single/aggregated/agglomerated/ network structures within the slurry[2].Furthermore, the non-destructive nature of electrochemical impedance spectroscopy facilitates in-situ measurements using a flow cell to investigate structural changes under applied shear forces and aging effects under steady-state conditions. Preliminary investigations into the correlation between impedance and particle dispersibility pave the way for future evaluations under both steady-state and shear forces (various flow conditions), offering a promising avenue for optimizing electrode slurry manufacturing processes. We also investigated the dispersibility of carbon particles in Li-ion conducting electrolyte media to differentiate the effect of dispersibility. This comprehensive approach not only highlights the critical role of carbon particle network structures within electrode slurries but also presents a meaningful impact in the field of lithium-ion battery technology.2. ExperimentalThe experimental approach involves increasing the content of acetylene black (AB) in non-aqueous binder suspensions as well as Li-ion conducting liquid from 0.3 wt.% to 10 wt.%. Electronic conductivity is evaluated using a specially designed cell for electrochemical impedance spectroscopy (EIS) under steady state and flow conditions. Analysis of slurry intermediate states with varying AB solid content provides insights into structural changes and better knowing the primary/aggregates and agglomerated states of AB, including network formation. Rheological properties of the slurry are also analyzed to establish the relationship between AB particle dispersion and solid content. Additionally, particle sedimentation is assessed in relation to aging. To validate findings, the slurry is freeze-dried between microslides for morphological observations and rheology analysis.3. Results and DiscussionAs depicted in Figure 1, at low carbon concentrations, the electrochemical response exhibits characteristics akin to an electrochemical capacitor, mainly influenced by the resistance of the polymeric binder. However, at higher carbon concentrations, a well-defined electronic percolating network forms, leading to an impedance response shift from a linear pattern to a semicircular shape. The mixing process of electrode particles induces shear stress, potentially fragmenting the network structure. Moreover, particle sedimentation may contribute to the formation of aggregates and agglomerates. Hence, understanding and optimizing the carbon percolation network are crucial for ensuring effective electronic conduction and promoting homogeneity, even under varying flow conditions. Investigation of slurry impedance degradation with increasing AB content via EIS, supported by morphological observations and rheology analysis, yields valuable insights into enhancing lithium-ion battery performance. The study delves into comprehending the electron conduction network under steady state and various slurry flow rates, along with the rheological properties of electrode slurries. The impedance measurement results reveal a correlation between impedance and particle dispersibility, with the formation of a three-dimensional network structure at higher AB concentrations. Structural changes over time in the slurry with a three-dimensional network structure indicate further development, underscoring the significance of optimizing carbon percolation networks for enhanced electrochemical performance in lithium-ion battery electrodes.4. ConclusionThis study highlights the critical role of carbon conductive particles in lithium-ion battery electrode slurries. Optimizing their dispersion and network structure is pivotal for achieving high conductivity and enhancing electrochemical performance. These findings hold significant potential for advancing lithium-ion battery technology towards greater efficiency and performance and also stand as a best slurry quality check when shifting to new electrode material combinations. References (1) J. K. Padarti, S. Hirai, H. Sakagami, T. Matsuda, T. Ohno, J. Ceram. Soc. Japan, 130, 832 (2022).(2) J. K. Padarti, Ľ. Gabániová, S. Hirai, T. Matsuda, H. Suzuki, T. Ohno, 第59回粉体に関する討論会, December (2022). Figure 1

Continuous bioprocessing has the inherent advantage of higher productivity, which can facilitate implementation of small process trains resulting in cost-effective, lean, and agile manufacturing facilities. Impressive technological advances to enable continuous bioprocessing have been made in the recent past and were discussed at ECI's Integrated Continuous Biomanufacturing (ICB) III Conference (Cascais, Portugal, 17-21 September 2017) chaired by Suzanne Farid (UCL), Chetan Goudar (Amgen), Paula Alves (iBET), and Veena Warikoo (ex-Sanofi, currently Roche). The ICB III conference brought together leading scientists and engineers from academia, industry and regulatory authorities that are actively engaged in continuous bioprocessing to debate how industrialized our sector can become and potential scenarios where continuous platforms will better serve our needs. The conference participants were surveyed on a number of questions related to continuous bioprocessing and a summary of some of the key responses is highlighted in Figure 1. The profile of the survey respondents were approximately 50% biopharma companies, 30% academia, 15% vendors, and 5% government organisations with the majority in process development, manufacturing science and technology (MSAT) or research roles. The survey tackled the question of what a facility of the future might look like and the majority envisioned hybrid facilities with batch and continuous operations, with scale-out or numbering up principles rather than large scaled-up facilities and with ballroom designs. The survey aimed to assess also how many companies were serious about implementing continuous processes. The survey revealed that 40% of respondents were developing continuous and integrated platforms for products starting in Phase 1 and 20% in Phase II or post approval. This suggests a significant shift from previous conferences where there was a large effort in evaluating and demonstrating the potential of continuous processes without necessarily commitment in clinical programs. Hurdles and challenges were addressed from two perspectives, the conceptual design phase and commercialization. During early decision-making, the top 4 hurdles to implementing continuous facility design concepts were complexity and risk (65%), lack of GMP technologies (50%), comparability or quality issues (30%) and management buy-in (28%). Moving toward commercialization, the keywords that captured major challenges were validation, control, quality, and definition as the sector comes to terms with new equipment and a greater need for automation and mechanisms to deal with deviations. Regarding the most important areas of Process Analytical Technologies needed for successful continuous and integrated bioprocessing, popular responses were online and inline sensors, monitoring, models for process understanding, and robustness capabilities. On the most effective mechanism for developing new processes and equipment for ICB, the majority of respondents indicated that collaborative ways forward were preferred with vendors or utilizing open-source technologies developed in consortia. This Special Issue of BTJ on the conference theme of “Integrated Continuous Biomanufacturing: Industrialization on the Horizon” captures some of the presentations and discussions from the ICB III conference across a range of topics from state-of-the-art technologies in continuous upstream, downstream, and drug product unit operations through to end-to-end continuous processes. Case studies for the implementation of continuous platforms were presented for these processes covering perspectives such as scale-down mimics, control strategies, and cost of goods analysis. On the upstream front, there are 4 articles on perfusion cell culture. More specifically, Sanofi1 demonstrate reduced process and product heterogeneity in perfusion cell culture compared to fed-batch processes, ETH in collaboration with Merck Biopharma and Jagiellonian University Poland2 illustrate how to improve perfusion performance by growth inhibition, Boehringer Ingelheim3 tackle product retention issues using larger pore size membranes attached to perfusion bioreactors, and Merck KGaA4 provide recommendations for comparison of productivity between fed-batch and perfusion processes. On the downstream front, Pall Biotech5, 6 explore the productivities and cost savings with continuous chromatography setups. There are also two contributions providing insights on continuous virus inactivation from Boehringer Ingelheim7 and MilliporeSigma8 with an additional Commentary from BOKU (Austria).9 On the end-to-end front, MedImmune10 share experiences implementing a fully integrated continuous antibody process with commentary on productivity and cost of goods impacts. In addition to biologics drug substance manufacture, the Special Issue also includes a Review article from Insmed and UCL11 investigating how some of the biopharma continuous concepts might apply to liposomal drug products. We sincerely thank all the authors and reviewers for their contributions to this Special issue as well as all those that contributed to the success of the ICB III conference. We look forward to the upcoming ECI ICB IV conference (Brewster (Cape Cod), Massachusetts, October 6-10, 2019) to bring together the community once again and advance the adoption of continuous bioprocessing in the sector. Prof Suzanne S Farid Department of Biochemical Engineering University College London, UK E-mail: s.farid@ucl.ac.uk

Continuous granulation in the pharmaceutical industry

Foaming process can be monitored under batch or continuous flows conditions. In the batch process, foaming is time-dependent and the foaming efficiency is controlled by the operator. On the other hand, in the continuous process, the foaming efficiency is only monitored by gas and liquid flow rates. The aim of this work is to compare the two technologies to perform porous scaffold biomaterial based on chitosan (a biocompatible polysaccharide) as well as calcium (Ca2+) and silica (SiO2) (two osteogenesis compounds). Diverse recipes using chitosan (CS) solution (2% (w/v)) in acetic acid (1% (v/v in distilled water)) mixed with whey protein isolate (WPI) (2% (w/v)) as natural surfactant were studied. They were supplemented or not by hydroxyapatite powder (HAp) and tetraethyl orthosilicate (TEOS). A jacketed narrow annular gap unit (NAGU) was used to perform the continuous foaming process. For all experimentations, the mixture flow rate was maintained at 30 mL min-1. The influence of operating conditions such as gas and liquid flow rates was studied to obtain foams and final scaffold material with different densities and porosities. Some other recipes followed foaming under batch conditions. Generally, the recipes were placed in a vessel under mixing allowing the gas phase to come from the roof of the vessel. In this case, it becomes very difficult to control the density and the size distribution of bubbles in the final product. In both cases, liquid foams were analysed (density, bubble size distribution) and then freeze-dried for mechanical and porosity investigations using the dynamic mechanical analysis (DMA) system and scanning electron microscopy (SEM). It has been shown that the controlled injected gas affected the continuous phase, resulting in a lighter and higher porous structure, a more homogeneous appearance, and a more uniform distribution of osteogenesis components compared to one obtained using batch operation. The obtained porous materials exhibited good properties (porosity, interconnectivity, and good HAp and silica distribution) and potential for future bone regeneration applications.

A real-time, high-throughput visualization technique for heterogeneity in lithium-ion battery (LIB) electrodes is necessary to understand battery performance on a mechanistic level. Our group, along with others, has seen that battery performance is governed by short range (<20 um) electron transfer between the active material and carbon binder domain (CBD) within electrodes [1]–[3]. Available imaging techniques for visualizing the electronic connectivity of LIB electrodes are limited to nanoscale, single particle resolutions using sophisticated synchrotron X-ray or electron microscopy [4]–[6]. Optical microscopy offers the correct spatial resolution for visualizing the submicron connection of active particles to CBD, but is limited by colorimetry of electrode materials- with graphite being the exception due to its visible color change during lithiation [7]. There is a rapidly growing body of research interested in studying the ionic diffusion pathways of Li-ion using operando optical microscopy, however none currently exist for studying the submicron electronic connectivity through a facile, operando approach- especially under a industrially applicable lens [8]. To the best of our knowledge, this study presents the first spatially- and time- resolved technique for visualizing the electronic connectivity of commercial LIB electrodes using operando electrochemical fluorescent microscopy (EFM). This technique relies on the principle of electrofluorochromism, which we use to our advantage for a simple electrochemical system involving heterogeneous electron transfer. This allows us to use fluorescence as a real-time tracker for electronic heterogeneity, where electronic ‘dead-zones’ present as non-fluorescent regions in 2D images.Using our technique, we visualize commonly used commercial LIB electrodes (carbon content 1-4%, regimented processing), including NMC (LiNixMnyCo1-x-yO2), LFP (LiFePO4), and LCO (LiCoO2) against formulaically similar in-house made LIB electrodes (< 3.5% carbon content) as a proof of concept. We first validate the efficacy of this technique by testing commercial NMC, with a flaked off piece of active material, to show that areas of electronic discontinuities can in fact be represented by non-fluorescence (Fig.1.) We also find that when compared to commercial electrodes, those which are fabricated in house reveal isolated active particles, agglomerated carbon islands, and dead zones, undiscernible by brightfield imaging (Fig. 2.) Global feature extraction is performed on post-processed images to quantify electrode topology and evaluate electronic connectivity of active particles of battery electrodes, as well as heterogeneous mapping to determine the heterogeneity index of electrodes imaged. Testing our technique on low- and high- performing electrodes from an established library of coin-cell data allows for a straightforward way of correlating performance metrics to heterogeneity features. This quick (<1hr), reproducible visualization technique is general enough to be used to study the electronic connectivity of emerging new battery electrodes, as well as verify commercially available ones. Using this approach to verify LIB electrodes prior to assembly could save months to years of battery testing by being used as an alternative to lengthy full cell testing.[1] S. L. Morelly, N. J. Alvarez, and M. H. Tang, “Short-range contacts govern the performance of industry-relevant battery cathodes,” Journal of Power Sources, vol. 387, pp. 49–56, May 2018, doi: 10.1016/j.jpowsour.2018.03.039.[2] R. M. Saraka, S. L. Morelly, M. H. Tang, and N. J. Alvarez, “Correlating Processing Conditions to Short- and Long-Range Order in Coating and Drying Lithium-Ion Batteries,” ACS Appl. Energy Mater., vol. 3, no. 12, pp. 11681–11689, Dec. 2020, doi: 10.1021/acsaem.0c01305.[3] J. Entwistle, R. Ge, K. Pardikar, R. Smith, and D. Cumming, “Carbon binder domain networks and electrical conductivity in lithium-ion battery electrodes: A critical review,” Renewable and Sustainable Energy Reviews, vol. 166, p. 112624, Sep. 2022, doi: 10.1016/j.rser.2022.112624.[4] S. Li et al., “Mutual modulation between surface chemistry and bulk microstructure within secondary particles of nickel-rich layered oxides,” Nat Commun, vol. 11, no. 1, Art. no. 1, Sep. 2020, doi: 10.1038/s41467-020-18278-y.[5] P.-C. Tsai et al., “Single-particle measurements of electrochemical kinetics in NMC and NCA cathodes for Li-ion batteries,” Energy Environ. Sci., vol. 11, no. 4, pp. 860–871, Apr. 2018, doi: 10.1039/C8EE00001H.[6] A. Singer et al., “Nucleation of dislocations and their dynamics in layered oxide cathode materials during battery charging,” Nat Energy, vol. 3, no. 8, Art. no. 8, Aug. 2018, doi: 10.1038/s41560-018-0184-2.[7] Y. Yamagishi, H. Morita, Y. Nomura, and E. Igaki, “Visualizing Lithiation of Graphite Composite Anodes in All-Solid-State Batteries Using Operando Time-of-Flight Secondary Ion Mass Spectrometry,” J. Phys. Chem. Lett., vol. 12, no. 19, pp. 4623–4627, May 2021, doi: 10.1021/acs.jpclett.1c01089.[8] A. J. Merryweather, C. Schnedermann, Q. Jacquet, C. P. Grey, and A. Rao, “Operando optical tracking of single-particle ion dynamics in batteries,” Nature, vol. 594, no. 7864, Art. no. 7864, Jun. 2021, doi: 10.1038/s41586-021-03584-2. Figure 1

A real-time, high-throughput visualization technique for heterogeneity in lithium-ion battery (LIB) electrodes is necessary to understand battery performance on a mechanistic level. Our group, along with others, has seen that battery performance is governed by short range (<20 um) electron transfer between the active material and carbon binder domain (CBD) in electrodes [1]–[3]. Available imaging techniques for visualizing the electronic connectivity of LIB electrodes are limited to nanoscale, single particle resolutions using sophisticated synchrotron X-ray or electron microscopy [4]–[6]. Optical microscopy offers the correct spatial resolution for visualizing the submicron connections of active particles to CBD, but is limited by the colorimetry of electrode materials- with graphite being the exception due to its visible color change during lithiation [7]. There is a rapidly growing body of research interested in studying the ionic diffusion pathways of Li-ion using operando optical microscopy, however none currently exist for studying the submicron electronic connectivity using an operando approach- especially under a industrially applicable lens [8]. To the best of our knowledge, this study presents the first spatially- and time- resolved technique for visualizing the electronic connectivity of commercial LIB electrodes using operando electrochemical fluorescent microscopy (EFM). This technique relies on the principle of electrofluorochromism, which we use to our advantage for a simple electrochemical system involving heterogeneous electron transfer. This allows us to use fluorescence as a real-time tracker for electronic heterogeneity, where electronic ‘dead-zones’ present as non-fluorescent regions in 2D images.Using this technique, we visualize commonly used commercial LIB electrodes (carbon content 1-4%, regimented processing), including NMC (LiNixMnyCo1-x-yO2), LFP (LiFePO4), and LCO (LiCoO2) against formulaically similar in-house made LIB electrodes (< 3.5% carbon content) as a proof of concept. We first validate the efficacy of this technique by testing commercial NMC, with a flaked off piece of active material, to show that areas of electronic discontinuities can in fact be represented by non-fluorescence (Fig.1.) We also find that when compared to commercial electrodes, those which are fabricated in house reveal isolated active particles, agglomerated carbon islands, and dead zones, undiscernible by brightfield imaging (Fig. 2.) Global feature extraction is performed on post-processed images to quantify electrode topology and evaluate electronic connectivity of active particles of battery electrodes, as well as heterogeneous mapping to determine the heterogeneity index of electrodes imaged. Testing our technique on low- and high- performing electrodes from an established library of coin-cell data allows for a straightforward way of correlating performance metrics to heterogeneity features. This quick (<1hr), reproducible visualization technique is general enough to be used to study the electronic connectivity of emerging new battery electrodes, as well as verify commercially available ones. Using this approach to verify LIB electrodes prior to assembly could save months to years of battery testing by being used as an alternative to lengthy full cell testing.[1] S. L. Morelly, N. J. Alvarez, and M. H. Tang, “Short-range contacts govern the performance of industry-relevant battery cathodes,” Journal of Power Sources, vol. 387, pp. 49–56, May 2018, doi: 10.1016/j.jpowsour.2018.03.039.[2] R. M. Saraka, S. L. Morelly, M. H. Tang, and N. J. Alvarez, “Correlating Processing Conditions to Short- and Long-Range Order in Coating and Drying Lithium-Ion Batteries,” ACS Appl. Energy Mater., vol. 3, no. 12, pp. 11681–11689, Dec. 2020, doi: 10.1021/acsaem.0c01305.[3] J. Entwistle, R. Ge, K. Pardikar, R. Smith, and D. Cumming, “Carbon binder domain networks and electrical conductivity in lithium-ion battery electrodes: A critical review,” Renewable and Sustainable Energy Reviews, vol. 166, p. 112624, Sep. 2022, doi: 10.1016/j.rser.2022.112624.[4] S. Li et al., “Mutual modulation between surface chemistry and bulk microstructure within secondary particles of nickel-rich layered oxides,” Nat Commun, vol. 11, no. 1, Art. no. 1, Sep. 2020, doi: 10.1038/s41467-020-18278-y.[5] P.-C. Tsai et al., “Single-particle measurements of electrochemical kinetics in NMC and NCA cathodes for Li-ion batteries,” Energy Environ. Sci., vol. 11, no. 4, pp. 860–871, Apr. 2018, doi: 10.1039/C8EE00001H.[6] A. Singer et al., “Nucleation of dislocations and their dynamics in layered oxide cathode materials during battery charging,” Nat Energy, vol. 3, no. 8, Art. no. 8, Aug. 2018, doi: 10.1038/s41560-018-0184-2.[7] Y. Yamagishi, H. Morita, Y. Nomura, and E. Igaki, “Visualizing Lithiation of Graphite Composite Anodes in All-Solid-State Batteries Using Operando Time-of-Flight Secondary Ion Mass Spectrometry,” J. Phys. Chem. Lett., vol. 12, no. 19, pp. 4623–4627, May 2021, doi: 10.1021/acs.jpclett.1c01089.[8] A. J. Merryweather, C. Schnedermann, Q. Jacquet, C. P. Grey, and A. Rao, “Operando optical tracking of single-particle ion dynamics in batteries,” Nature, vol. 594, no. 7864, Art. no. 7864, Jun. 2021, doi: 10.1038/s41586-021-03584-2. Figure 1

Model-assisted process design for better evaluation and scaling up of continuous downstream bioprocessing

Due to high scrap rates and manufacturing costs, battery cell production requires continuous process optimization. The potential for material efficiency is particularly high in electrode production, specifically in the mixing process. Challenges in the continuous mixing process are related to automation and traceability of material. As one of the most relevant parameters, the residence time of particles must be known, otherwise it is not possible to make a statement about the traceability of the slurry ingredients. Without knowledge of the residence time distribution (RTD), autonomous process control or traceability of battery cells and their components is not possible. The influence of process and material parameters on the RTD of the continuous mixing process in battery cell production is being systematically investigated. Based on a design of experiment, the mean residence time and the RTD are determined for a graphite‐based anode slurry by manipulating the conductivity by adding a tracer. Special attention is given to the properties of the tracer as well as the tracer behavior within the mixing process. The influence of different parameters is analyzed based on the conductivity changes. It is shown that the parameters mass flow and solid content have the greatest influence on the RTD.

The increasing demand for energy storage has led to continual improvements in materials for battery electrodes. However, the overall processing of these materials into devices and the need for composite electrodes has remained essentially the same. Currently, the optimal processing conditions are determined through time-, labor-, and capital-intensive trial and error. Determining the fundamental particle and electrochemical physics that result in high-performance composite electrodes is so far an untapped field of potential. Our work strives to fully understand from a rheological perspective the interactions of components in electrode slurries. These insights will allow the manufacturing process of new materials to be accelerated, resulting in faster, more efficient implementation of new materials into effective electrodes. The mixing, coating, drying and calendaring of active material, conductive additive, and polymer binder in solvent affect the final battery microstructure. Although it is well-known that the electrode slurry microstructure impacts the final battery performance, there is little agreement on what constitutes a favorable microstructure [1,2]. Slurries may be broadly divided into two rheological categories, fluids and gels. In a fluid-like system, suspended particles typically interact via hydrodynamic forces. In a colloidal gel, particles form a percolating network that extends across the volume of the system through surface or depletion interactions. In this work, we study a model system of lithium nickel manganese cobalt oxide (NMC), carbon black, polyvinyldifluoride (PVDF), and 1-methyl-2-pyrrolidinone (NMP) to determine the effects of slurry microstructure on battery performance. Slurries are characterized using small-amplitude oscillatory shear (SAOS) in which a constant strain is applied at increasing angular frequencies and the viscous and elastic components of the stress are determined as a function of frequency (frequency sweep). Figure 1 compares the frequency sweeps for a fluid system and a gel system formed with micron-sized and nano-sized active material, while maintaining constant PVDF molecular weight, carbon black, and mixing parameters. A fluid system is depicted by G” larger than G’. Gel systems are typically observed when G’ dominates. Suspended micron-sized active material does not form a gel in the presence of polymer binder. However, the addition of a critical volume fraction of free nano-sized carbon additive causes the suspension to gel. We find that the critical gelation volume fraction of free carbon black (40nm) is equal to 0.5 vol%. The typical quantity used in commercial battery slurry recipes is 2 vol% [3]. The amount of free carbon is highly dependent on the commonly used dry-mixing step, where active material and conductive additive are blended together. It has been shown that dry –mixing causes conductive additive to coat the active material reducing the amount of free carbon in the suspension. In other words, in the absence of dry-mixing, all the carbon is above the critical concentration and readily forms a gel, i.e. percolating network. However, depending on the dry-mixing conditions, enough carbon is coated on the active material such that the amount of free carbon is too low to form a colloidal gel. By varying the dry mixing step of slurry preparation, a wide range of slurry microstructures can be achieved without varying the total carbon concentration. Contrary, nano-sized active material readily forms a gel due to its size and large volume fraction in the electrode slurry. Slurries with characterized microstructures are coated, dried, and calendered into electrodes in order to relate slurry microstructure to electronic conductivity, life cycle and rate capability of the processed electrodes. Measurements of the electronic conductivity and battery performance show that gel slurries form electrodes with higher initial conductivity and lower porosity. Electrodes from gel slurries also cycle longer and have higher capacities than fluid slurries. We hypothesize that the continuous carbon network is necessary to provide sufficient electronic conductivity. Future work will investigate the dependence of performance and electrode tortuosity on slurry microstructure and the effects of drying parameters on battery performance.

The capture of CO2 from the atmosphere via Direct Air Capture using solid supported-amine sorbents is an important option to reduce the atmospheric concentration of CO2. It addresses CO2 emissions from dispersed sources and delivers a location independent, sustainable carbon source. This study evaluates the possibility for a continuous adsorption process for direct air capture in a radial flow contactor, using both batch and continuous mode of operation. Gas and solid flow were varied to determine hydrodynamic feasible operating conditions. The operation modes are compared by their capture efficiencies in the optimal adsorption time range of 0.5 tstoB and 1.5 tstoB. A 15–25% lower capture efficiency is found for a continuous process compared to a batch process in the relevant range for direct air capture. This decline in gas-solid contact efficiency is more pronounced at longer adsorption time and higher superficial gas velocity. Overall, a batch process is preferred over a continuous process in the majority of operating conditions.

There is a growing interest in continuous biopharmaceutical processing due to the advantages of small footprint, increased productivity, consistent product quality, high process flexibility and robustness, facility cost-effectiveness, and reduced capital and operating cost. To support the decision making of biopharmaceutical manufacturing, comparisons between conventional batch and continuous processing are provided. Various process unit operations in different operating modes are summarized. Software implementation, as well as computational methods used, are analyzed pointing to the advantages and disadvantages that have been highlighted in the literature. Economic analysis methods and their applications in different parts of the processes are also discussed with examples from publications in the last decade. The results of the comparison between batch and continuous process operation alternatives are discussed. Possible improvements in process design and analysis are recommended. The methods used here do not reflect Lilly's cost structures or economic evaluation methods. This paper provides a review of the work that has been published in the literature on computational process design and economic analysis methods on continuous biopharmaceutical antibody production and its comparison with a conventional batch process.

Current processing standards for battery electrode slurries are determined through time-, labor-, and capital-intensive trial and error. The effect of these processing conditions on battery performance is acknowledged, but not fully understood. The field of rheology, specifically the study of colloidal suspensions, holds a wealth of knowledge about the particle-particle interactions that develop in fluids very similar to battery electrode slurries. Our work uses rheology to measure and understand changes in the viscoelastic properties of battery slurries as a function of mixing parameters, and then utilizes these changes as indicators of the final battery performance and structure. We are, more specifically, interested in the dry mixing of conductive additive and active material, due to its documented ability to change the battery slurry’s viscoelastic behavior, e.g. the potential to change the slurry from a colloidal gel to viscoelastic fluid [1,2]. Slurry microstructure is argued to have a large impact on battery performance due to the persisting structure (particle dispersion) during the subsequent processing steps. Dry-mixing is thought to impact battery performance by depositing conductive additive on the surface of the micron-sized active material, increasing overall electronic conductivity of the electrode. The goal of this work is to decouple whether increased electronic conductivity, the initial electrode microstructure (particle dispersion), or a synergism of the two is responsible for increases in battery performance. By keeping the total concentration of carbon constant, we generate electrode slurries with different degrees of free carbon, i.e. carbon that can form a volume spanning colloidal network (colloidal gel). The different degrees of microstructure and carbon deposited on the active material will determine if there exists an optimum in battery performance. Our initial work investigates the extremes of dry-mixing. This has allowed us to investigate systems where all of the available carbon is free to aggregate and form a gel network (long-range electron pathways) and all of the available carbon has been deposited onto the active material (short-range electron pathways). This has allowed us to effectively decouple the individual impacts of short-range and long-range electron pathways on battery performance. Rate capability tests of batteries made from each system show that long-range electron pathways have a greater beneficial impact than short-range pathways. These initial findings in terms of short- and long-range electron pathways run contrary to current literature findings [1,2], which have indicated that improvement of short-range electron pathways is needed for improved performance. Our future work will investigate methods to optimize these short-range contacts while maintaining the beneficial long-range contacts that we have observed. [1]W. Bauer, D. Noetzel, Ceram. Int. 40 (2014) 4591. [2]G.-W. Lee, J.H. Ryu, W. Han, K.H. Ahn, S.M. Journal of Power Sources 195 (2010) 6049–6054.

There is growing interest in the possibility of developing truly continuous processes for the large-scale production of high value biological products. Continuous processing has the potential to provide significant reductions in cost and facility size while improving product quality and facilitating the design of flexible multi-product manufacturing facilities. This paper reviews the current state-of-the-art in separations technology suitable for continuous downstream bioprocessing, focusing on unit operations that would be most appropriate for the production of secreted proteins like monoclonal antibodies. This includes cell separation/recycle from the perfusion bioreactor, initial product recovery (capture), product purification (polishing), and formulation. Of particular importance are the available options, and alternatives, for continuous chromatographic separations. Although there are still significant challenges in developing integrated continuous bioprocesses, recent technological advances have provided process developers with a number of attractive options for development of truly continuous bioprocessing operations.