Depth Filtration Research Articles

Optimization of filter structures by evolutionary strategies

The increasing pressure drop of filter media during the capture of solid particles is directly correlated to the energy consumption. It is largely based on the microstructure of the media, especially with regard to the selected porosity gradient. The development of new filter media optimized for separation efficiency and energy consumption is based mainly on experimental work. The use of evolutionary algorithms inspired by nature is of particular interest for the optimization of filter media, as a large number of non-linear influencing factors can be processed. However, a large number of simulations is required for successful application in order to reproduce the natural process of mutation and individual selection. Most numerical simulations of filtration properties are limited due to the high computing power required, making them unsuitable in this context. Therefore, a 1D simulation with low computing power requirements was used in this paper to simulate the loading of a filter medium with particles. This approach enabled the rapid calculation of the loading of different filter media structures, and was coupled with an evolutionary algorithm with the aim of optimizing the porosity gradient. The algorithm was tested on different particle size distributions, which represented different operating conditions. The porosity gradients of the optimized filters was in the form of an inverse square function, leading to a much more homogenous, microscopic loading with particles. Due to the significantly improved utilization of the filter depth compared to a reference medium, a much slower increase in pressure difference could be obtained with a similar filtration efficiency, resulting in increased quality factors of 30% and higher. The optimization of an operating point took about 24 hours on a standard desktop PC and could be extended to other structural parameters of the filter medium apart from the porosity gradient. This shows the potential for a broad application in the selection and optimization of filter media.

Production of recombinant vesicular stomatitis virus-based vectors by tangential flow depth filtration

Cell culture-based production of vector-based vaccines and virotherapeutics is of increasing interest. The vectors used not only retain their ability to infect cells but also induce robust immune responses. Using two recombinant vesicular stomatitis virus (rVSV)-based constructs, we performed a proof-of-concept study regarding an integrated closed single-use perfusion system that allows continuous virus harvesting and clarification.Using suspension BHK-21 cells and a fusogenic oncolytic hybrid of vesicular stomatitis virus and Newcastle disease virus (rVSV-NDV), a modified alternating tangential flow device (mATF) or tangential flow depth filtration (TFDF) systems were used for cell retention. As the hollow fibers of the former are characterized by a large internal lumen (0.75 mm; pore size 0.65 μm), membrane blocking by the multi-nucleated syncytia formed during infection could be prevented. However, virus particles were completely retained. In contrast, the TFDF filter unit (lumen 3.15 mm, pore size 2–5 μm) allowed not only to achieve high viable cell concentrations (VCC, 16.4–20.6×106 cells/mL) but also continuous vector harvesting and clarification. Compared to an optimized batch process, 11-fold higher infectious virus titers were obtained in the clarified permeate (maximum 7.5×109 TCID50/mL).Using HEK293-SF cells and a rVSV vector expressing a green fluorescent protein, perfusion cultivations resulted in a maximum VCC of 11.3×106 cells/mL and infectious virus titers up to 7.1×1010 TCID50/mL in the permeate. Not only continuous harvesting but also clarification was possible. Although the cell-specific virus yield decreased relative to a batch process established as a control, an increased space-time yield was obtained.Key points• Viral vector production using a TFDF perfusion system resulted in a 460% increase in space-time yield• Use of a TFDF system allowed continuous virus harvesting and clarification• TFDF perfusion system has great potential towards the establishment of an intensified vector production

Compartmentalization transformation of Fe2+, Mn2+ and NH4+ in groundwater: A comparative research containing experimental medium and functional genera profiling derived from experiment data

Contamination of soluble iron (Fe2+), manganese (Mn2+), and ammonium (NH4+) in groundwater is prevalent, particularly in Northeast China. This study aims to elucidate the intricate biological and physical-chemical reactions involved in the sequential transformation of three target contaminants. Two dynamic column simulations were used to compare quartz sand filtration (QSF) system with riverbank filtration (RBF) system to assess the interactions and respective contributions of the reactions involved in transforming process. Similar pattern of transformation vertical compartmentalization in two systems along the filter depth were founded, and the Fe2+ transformation was mainly distributed in the upper part, while NH4+ and Mn2+ occurred primarily in the downstream sections. The average transformation rate of Fe2+, Mn2+ and NH4+ in RBF system was 84.52 %, 47.68 % and 67.95 %, respectively, which was 5.20 %, 11.43 % and 23.06 % higher than in QSF system. The dominant transformation process for Fe2+ in RBF involved chemical oxidation, bio-oxidation and adsorption. The lower transformation rate for Mn2+ was attributed to abiotic homogenous oxidation limitation and negative affect derived from high concentration of NH4+ with high nitrification rate in RBF system. Nitrification by Nitrosomonas and Nitrospira was critical NH4+ transformation mechanism in RBF system, while the adsorption by iron and manganese oxide and aerobic denitrification were contributed strongly to NH4+ transformation in QSF system. Furthermore, the spatial distribution of functional bacterial genera was in good consistent with the transformation compartmentalization of three target contaminants in both systems, and similar microbial community structure reflected the domestication effect of groundwater chemistry on functional bacteria.

Highly permeable nanofibrous polyamide membranes for multi-component wastewater treatment: Exploration of multiple separation mechanism

Multi-component wastewater containing a variety of organic toxins, e.g., dyes and inorganic particulates induces serious environmental concerns, which must be addressed by innovative approaches instead of conventional chemical and physical processes, which are limited by purification efficiency, secondary pollution, and cost-effectiveness. Therefore, it is important to find new avenues of purification methods that are both sustainable and effective. Ultra-fine nanofibrous microfiltration membranes were fabricated by multi-nozzle electrospinning of polyamide-66 (PA-66) and were employed to remove 0.2-μm-nanoparticles and dyes simultaneously from wastewater through filtration and dynamic adsorption performance, in an attempt to discover a one-step filtration system for both dyes and nanoparticles. The fiber diameter and surface morphology of the nanofibrous membranes varied with the concentrations of polyamide solutions, where the ultra-fine nanofibrous membrane exhibited optimum mechanical properties at a specific concentration of PA-66 (11 wt%). The nanofibrous membranes had adsorption capabilities of 133.3 and 204.5 mg/g, respectively, against both anionic dyes (e.g., metanil yellow) and cationic dyes (e.g., chrysoidine), respectively. The membrane also selectively filtrated fine nanoparticles with a nearly 100% rejection ratio. A multiple separation mechanism, including adsorption based on electrostatic interaction, hydrogen bonding interaction, and hydrophobic interaction, as well as depth filtration, was proposed. As an applicable demonstration, the spiral wound cartridge fabricated by PA-66 nanofibrous membrane was used for a simulated multi-component wastewater treatment that contained dyes and nanoparticles of different concentrations. During the multicomponent test at flow rate 1 mL/min, a rejection rate of 97% and greater than 99% were achieved against dyes and nanoparticles, respectively.

Kinect-based objective assessment of the acute levodopa challenge test in parkinsonism: a feasibility study.

The acute levodopa challenge test (ALCT) is an important and valuable examination but there are still some shortcomings with it. We aimed to objectively assess ALCT based on a depth camera and filter out the best indicators. Fifty-nine individuals with parkinsonism completed ALCT and the improvement rate (IR, which indicates the change in value before and after levodopa administration) of the Movement Disorder Society-Sponsored Revision of the Unified Parkinson's Disease Rating Scale part III (MDS-UPDRS III) was calculated. The kinematic features of the patients' movements in both the OFF and ON states were collected with an Azure Kinect depth camera. The IR of MDS-UPDRS III was significantly correlated with the IRs of many kinematic features forarising from a chair, pronation-supination movements of the hand, finger tapping, toe tapping, leg agility, and gait (rs = - 0.277 ~ - 0.672, P < 0.05). Moderate to high discriminative values were found in the selected features in identifying a clinically significant response to levodopa with sensitivity, specificity, and area under the curve (AUC) in the range of 50-100%, 47.22%-97.22%, and 0.673-0.915, respectively. The resulting classifier combining kinematic features of toe tapping showed an excellent performance with an AUC of 0.966 (95% CI = 0.922-1.000, P < 0.001). The optimal cut-off value was 21.24% with sensitivity and specificity of 94.44% and 87.18%, respectively. This study demonstrated the feasibility of measuring the effect of levodopa and objectively assessing ALCT based on kinematic data derived from an Azure Kinect-based system.

Examination of the Efficiency of Fabric Filter Media in Two-Stage Crossflow Pre-Filtration of Turbid Surface Water Using the Davies Flow Equation

Clogging of rapid sand filters during heavy rainfall causes surface water treatment plants to stop their operations until the river water turbidity decreases to a level that the rapid sand filter is capable of filtering. As clogging of rapid sand filters is impediment in surface water treatment, two-stage crossflow pre-filtration with fabric filter media (linen, crepe-backed satin, burlap, and cotton) was considered in a previous study by Davis and Ekwue (2020) as a possible solution. Pre-filtration with linen fabric filter medium was found to be the most efficient at retaining particles. The present paper incorporated properties of various fabrics previously measured and identified by Davis and Ekwue (2020) with the aim of identifying ideal fabric properties that were effective in removing particles from turbid water. Mechanisms of filtration (surface straining, depth filtration and cake filtration) depicted by each selected fabric during two-stage crossflow pre-filtration were identified and compared to the operation of standard filter media (absorbent, adsorbent, biological and woven). The Davies equation was used to calculate the flow of water through single layer and four layers of fabric filter media. Results indicate that no one specific fabric property could be used to proclaim a fabric as the ideal filter media, but rather all properties of the various fabric contribute to their performance during filtration.Linen fabric was once again determined as the fabric type most efficacious at retaining particles during two-stage crossflow pre-filtration of turbid river water and is therefore recommended.

Recombinant AAV Purification.

Purification of rAAV is a crucial unit operation of the AAV production process. It enables the capture of AAV and removal of contaminants such as host cell proteins, host cell DNA, and other cell culture-related impurities. Here we describe the purification of rAAV produced in insect cells Sf9/rBEV by immuno-affinity capture chromatography. The method is fully scale-amenable unlike other traditional purification methods based on ultracentrifugation. The method reported herein has two main steps: (1) the clarification of cell lysate by depth filtration and (2) the selective capture and single-step purification of AAV via immune-affinity chromatography. This purification method has been successfully implemented to purify the majority of wild-type AAV serotypes.

Harnessing graphene oxide-enhanced composite metal-organic frameworks for efficient wastewater treatment

The issue of carwash wastewater emerges as a pressing environmental concern on a global scale, primarily due to the intricate nature of its pollutants, which makes effective treatment a formidable challenge. In the face of this complex scenario, the pursuit of an efficient treatment methodology assumes paramount importance. In response to this complex scenario, this study embarked on an exploration of a novel polymeric adsorbent material synthesized from Zeolitic Imidazolate Framework-67, Zeolitic Imidazolate Framework-8, Polyethersulfone, and graphene oxide in a fixed-bed treatment system for carwash wastewater. The investigation encompassed three distinct filter column depths, measuring 8 cm, 12 cm, and 16 cm, respectively. With an increase in filter depth from 8 cm to 16 cm, notable improvements were observed in the removal efficiencies for most contaminants. Notably, oils/grease removal showed an increasing trend with column depth, reaching 95.4%, 98.6%, and 100% for 8 cm, 12 cm, and 16 cm depths, respectively. TSS and Turbidity removal efficiencies remained consistently high at 100% across all depths, showcasing effective removal of solid particulate matter. Copper and Zinc removal efficiencies increased with deeper column depths, reaching values of 80.4%–89.9% and 79.6%–90.3%, respectively. Surfactants exhibited efficient removal, with values ranging from 90.6% to 96.6%. Total Dissolved Solids removal efficiency increased from 71.6% to 83.4% as column depth increased. Similarly, Chemical Oxygen Demand, Biochemical Oxygen Demand, total organic carbon, and phosphates removal efficiencies showed improvement with increasing column depth, reaching values of 95.4%, 98.3%, 98.8%, and 89.3%, respectively. Moreover, The composite MOF beads demonstrated significant adsorption capacities in carwash wastewater treatment, with a noteworthy 35.08 mg/g for Oils/Grease and 28.12 mg/g for Biochemical Oxygen Demand, highlighting their efficiency in removing hydrophobic contaminants and organic pollutants.The derived results highlight the potential of the composite material for carwash wastewater treatment towards advancing the field of wastewater treatment.

Vertical spatial denitrification performance and microbial community composition in denitrification biofilters coupled with water electrolysis.

In this study, a denitrification biofilter coupled with water electrolysis (DNBF-WE) was developed as a novel heterotrophic-hydrogen autotrophic denitrification system, which could enhance denitrification with limited organic carbon in the secondary effluent. The volumetric denitrification rate of DNBF-WE reached 152.16 g N m-3 d-1 (C/N = 2, I = 60 mA, and HRT = 5 h). Besides, the vertical spatial denitrification of DNBF-WE was explored, with the nitrate removal rate being 49.5%, 16.3%, and 29.3% in the top, middle, and bottom, respectively. The concentration of extracellular polymeric substances (EPSs) was consistent with the denitrification performance vertically. The high-throughput sequencing analysis results revealed that autotrophic denitrification bacteria (e.g. Thauera) gradually enriched along DNBF-WE from top to bottom. The functional gene prediction results illustrated the vertical stratification mechanisms of the denitrification. Both dissimilatory nitrate reduction and denitrification contributed to nitrate removal, and denitrification became more advantageous with an increase in the filter depth. The research on both the performance of DNBF-WE and the characteristics of microbial communities in the vertical zones of the biofilter may lay a foundation for the biofilter denitrification process in practice.

Evaluation of and period polynomial relations

Abstract In studying the depth filtration on multiple zeta values, difficulties quickly arise due to a disparity between it and the coradical filtration [9]. In particular, there are additional relations in the depth graded algebra coming from period polynomials of cusp forms for $\operatorname {\mathrm {SL}}_2({\mathbb {Z}})$ . In contrast, a simple combinatorial filtration, the block filtration [13, 28] is known to agree with the coradical filtration, and so there is no similar defect in the associated graded. However, via an explicit evaluation of $\zeta (2,\ldots ,2,4,2,\ldots ,2)$ as a polynomial in double zeta values, we derive these period polynomial relations as a consequence of an intrinsic symmetry of block graded multiple zeta values in block degree 2. In deriving this evaluation, we find a Galois descent of certain alternating double zeta values to classical double zeta values, which we then apply to give an evaluation of the multiple t values [22] $t(2\ell ,2k)$ in terms of classical double zeta values.

Proceedings of the 2023 Viral Clearance Symposium, Session 3: 2023 VCS New Modalities in Chromatography and Adsorptive Filters.

The session provided an update on the application and mechanistic understanding of intensified unit operations (e.g., mixed mode depth filters, mixed mode AEX) since the last conference in 2019. One of the key gaps identified in the 2019 Viral Clearance Symposium session on the topic was for more investigation required to achieve a clear understanding of the molecular mechanisms of virus removal and the relevance of different moleculés interactions including resin, virus, and product. Further investigation into worst-case conditions for these unit operations is also warranted. One of the key outcomes from that 2019 discussion was also that multimodal anion exchangers can have robust and effective virus removal, depending on process and impurities-an observation that was recapitulated with more specific case studies and evidenced by broader application of these chromatographic resins in late-stage regulatory filings.

Influence of filtration treatments on grapevine DNA traceability in wine

Wine authentication through grapevine DNA traceability could be affected by wine technological processing treatments. In this study, filtration treatments including depth filter treatment using kieselguhr, perlite and membrane filtration using different types and pore sizes (0.22 and 0.45 μm) were applied on ‘Nebbiolo’ wine at an experimental scale. We used ‘Nebbiolo’ because it is an important Italian winegrape variety used to produce high-quality wines. Phenolic composition and color properties of the treated wines were examined using spectrophotometric and HPLC methods, while grapevine DNA traceability was evaluated using PCR based assays. The filtration treatments, as expected, significantly decreased turbidity compared to the unfiltered control, although total phenolics, total flavonoids and total non-flavonoids were not significantly affected. A significant reduction of acetylated anthocyanins by 6.1%–43.3% was observed in filtered wines, which could account for the reduced in total anthocyanins and color intensity of these wines. Grapevine DNA was significantly reduced in filtered wine by 37.2%–99.7%, with the reduction rate depending mainly on the properties of filter material. Polyvinylidene difluoride (PVDF) membranes with a pore size of 0.22 μm showed highest reduction of grapevine DNA in wine, resulting in the failure of TaqMan® single nucleotide polymorphisms (SNPs)-based assays used to detect grape DNA in wines.

Intensified Influenza Virus Production in Suspension HEK293SF Cell Cultures Operated in Fed-Batch or Perfusion with Continuous Harvest.

Major efforts in the intensification of cell culture-based viral vaccine manufacturing focus on the development of high-cell-density (HCD) processes, often operated in perfusion. While perfusion operations allow for higher viable cell densities and volumetric productivities, the high perfusion rates (PR) normally adopted-typically between 2 and 4 vessel volumes per day (VVD)-dramatically increase media consumption, resulting in a higher burden on the cell retention device and raising challenges for the handling and disposal of high volumes of media. In this study, we explore high inoculum fed-batch (HIFB) and low-PR perfusion operations to intensify a cell culture-based process for influenza virus production while minimizing media consumption. To reduce product retention time in the bioreactor, produced viral particles were continuously harvested using a tangential flow depth filtration (TFDF) system as a cell retention device and harvest unit. The feeding strategies developed-a hybrid fed-batch with continuous harvest and a low-PR perfusion-allowed for infections in the range of 8-10 × 106 cells/mL while maintaining cell-specific productivity comparable to the batch control, resulting in a global increase in the process productivity. Overall, our work demonstrates that feeding strategies that minimize media consumption are suitable for large-scale influenza vaccine production.

Depth filtration for clarification of intensified lentiviral vector suspension cell culture.

Depth filtration significantly impacts efficiency of lentiviral (LV) vector purification process. However, it is often deprioritized in the overall scope of viral vector manufacturing process optimization. The demand for LV vectors has increased with the rise in disease indications, making it crucial to improve current manufacturing processes. Upstream bioreactor process intensification has enabled cell densities of over 107 viable cells/mL, creating challenges for harvest unit operations. The larger size of LV vectors and their physiochemical similarity to host cell-DNA (HC-DNA) and poor clarification performance causes significant challenges for the subsequent chromatography-based purifications. As a result, a robust and scalable harvest of LV process is needed, especially for LV in vivo therapeutic quality needs. In this study, we systematically evaluated the overlooked yet important issue of depth filtration systems to improve enveloped LV functional vector recovery. We found that an established depth filtration system in process A that provided 94% (n = 6) LV functional recovery could not be translated to intensified Process B cell culture. Hence, the depth filtration process became a bottleneck for the purification performance in an intensified process. We demonstrated an improvement in LV functional vector recovery from 34% to 82% via filter train optimization for an intensified suspension cell culture system (>107 cells/mL with higher titer), while still maintaining a loading throughput of ≥82 L/m2 and turbidity ≤20 NTU. It was demonstrated that the two or three-stage depth filtration scheme is scalable and more suitable for high cell density culture for large scale for LV manufacturing process.

Fiber chromatographic enabled process intensification increases monoclonal antibody product yield.

The most straightforward method to increase monoclonal antibody (mAb) product yield is to complete the purification process in less steps. Here, three different fiber chromatographic devices were implemented using a holistic approach to intensify the mAb purification process and increase yield. Fiber protein A (proA) chromatography was first investigated, but traditional depth filtration was not sufficient in reducing the contaminant load as the fiber proA device prematurely fouled. Further experimentation revealed that chromatin aggregates were the most likely reason for the fiber fouling. To reduce levels of chromatin aggregates, a chromatographic clarification device (CCD) was incorporated into the process, resulting in single-stage clarification of harvested cell culture fluid and reduction of DNA levels. The CCD clarified pool was then successfully processed through the fiber proA device, fully realizing the productivity gains that the fiber technology offers. After the proA and viral inactivation neutralization (VIN) hold step, the purification process was further intensified using a novel single-use fiber-based polishing anion exchange (AEX) material that is capable of binding both soluble and insoluble contaminants. The three-stage fiber chromatographic purification process was compared to a legacy five-step process of dual-stage depth filtration, bead-based proA chromatography, post-VIN depth filtration, and bead-based AEX chromatography. The overall yield from the five-step process was 60%, while the fiber chromatographic-enabled intensified process had an overall yield of 70%. The impurity clearance of DNA and host cell protein (HCP) for both processes were within the regulatory specification (<100 ppm HCP, <1 ppb DNA). For the harvest of a 2000 L cell culture, the intensified process is expected to increase productivity by 2.5-fold at clarification, 50-fold at the proA step, and 1.6-fold in polishing. Relative to the legacy process, the intensified process would reduce buffer use by 1088 L and decrease overall process product mass intensity by 12.6%.

Technoeconomic comparison of optimised bioreactor-filtration systems for mAb production

Primary post-cultivation biomass recovery (cell culture removal from API-rich solutions) is essential in biopharmaceutical manufacturing. Centrifugation and depth filtration are dominant industrial primary recovery technologies, but mechanistic dynamic models suitable for performance evaluation are scarce. This paper uses established literature models to present and analyse optimal operation strategies for integrated process designs of fed-batch or perfusion CHO bioreactors (for mAb cultivation via CHO cultures), with an explicit rotational disk (dynamic crossflow) filtration model (for primary recovery). A rigorous DAE filter model (Marke et al., 2020) is employed here, to evaluate system performance. Dynamic optimisation of bioreactor-filter systems has been completed for different bioreactor types, filter arrangements and feed manipulations, considering the same annual mAb plant production target. A technoeconomic analysis of optimal designs addresses industrial viability, confirming a clear cost advantage of fed-batch reactors combined with stacked membrane microfilters.

Cu fractions in Shiraz and Pinot Noir wines during bottle aging: rates of changes and capacity for conversion

The Cu fraction in wine associated with Cu(II)-organic acid complexes can suppress detrimental aromas attributed to hydrogen sulfide and methanethiol. However, the long-term stability of this Cu fraction (known as Cu fraction I) during bottle aging of red wine is not well understood. This study utilised Pinot Noir and Shiraz wines containing 0.43 ± 0.01 and 0.56 ± 0.02 mg/L respectively of total Cu, to which 0, 0.3 or 0.6 mg/L Cu(II) was further added immediately before bottling. The bottles were then stored at 14 °C for 1 yr. Cu fraction I concentrations were measured using two independent methods: i) stripping potentiometry, and ii) ICP-OES analysis of filtrate after diatomaceous earth depth filtration. Within the first 6 months of storage, Cu fraction I was found to decrease in all wines. Using stripping potentiometry, the first-order decay rates were found to be 0.012 ± 0.001 day-1 and 0.010 ± 0.001 day-1 for Pinot Noir and Shiraz respectively, corresponding to half-lives of 55 ± 4 and 67 ± 9 days. The decay rates for Shiraz versus Pinot Noir were similar for wines with different Cu addition rates, or when rates were determined using the different analysis techniques. Both wines had a high capacity for conversion of Cu fraction I to Cu fraction III during the 1-yr storage period, with 0.4-0.8 mg/L Cu forming Cu fraction III in the Pinot Noir, and 0.3-0.6 mg/L in the Shiraz. These conversion capacity ranges are higher than the typical Cu(II) additions made to wine during production. Overall, the results show that red wine has a large capacity for enabling the sulfide-binding of Cu-organic acid complexes during bottle aging and the conversion occurs at a relatively uniform rate with the concentration halving approximately every 2 months.

Optimization and application of caprylic acid precipitation in the purification of monoclonal antibody

In response to the market demand for therapeutic antibodies, the upstream cell culture scale and expression titer of antibodies have been significantly improved, while the production efficiency of downstream purification process is relatively fall behind, and the downstream processing capacity has become a bottleneck limiting antibody production throughput. Using monoclonal antibody mab-X as experimental material, we optimized the caprylic acid (CA) precipitation process conditions of cell culture fluid and low pH virus inactivation pool, and studied two applications of using CA treatment to remove aggregates and to inactivate virus. Based on the lab scale study, we carried out a 500 L scale-up study, where CA was added to the low pH virus inactivation pool for precipitation, and the product quality and yield before and after precipitation were detected and compared. We found that CA precipitation significantly reduced HCP residuals and aggregates both before and after protein A affinity chromatography. In the aggregate spike study, CA precipitation removed about 15% of the aggregates. A virus reduction study showed complete clearance of a model retrovirus during CA precipitation of protein A purified antibody. In the scale-up study, the depth filtration harvesting, affinity chromatography, low pH virus inactivation, CA precipitation and depth filtration, and cation exchange chromatography successively carried out. The mixing time and stirring speed in the CA precipitation process significantly affected the CA precipitation effect. After CA precipitation, the HCP residue in the low pH virus inactivation solution decreased 895 times. After precipitation, the product purity and HCP residual meet the quality criteria of monoclonal antibodies. CA precipitation can reduce the chromatography step in the conventional purification process. In conclusion, CA precipitation in the downstream process can simplify the conventional purification process, fully meet the purification quality criterion of mab-X, and improve production efficiency and reduce production costs. The results of this study may promote the application of CA precipitation in the purification of monoclonal antibodies, and provide a reference for solving the bottleneck of the current purification process.

Contaminant removal from plastic waste pyrolysis oil via depth filtration and the impact on chemical recycling: A simple solution with significant impact

Recycling of mixed plastic waste via pyrolysis and subsequent steam cracking towards light olefins is a promising solution for the ever-growing plastic waste crisis. However, the pyrolytic recycling pathway is still not established on industrial scale due to the large variety of pyrolysis oil contaminants that hamper the application in (petro-)chemical processes. In short, plastic waste pyrolysis oils are unfeasible for steam crackers without upgrading. In this work, depth filtration for the removal of particulate contamination from a post-consumer mixed polyolefin (MPO) pyrolysis oil was performed using three different filter media with different porosity. Comprehensive analyses using SEM-EDX of the retained particles as well as ICP-OES and GC × GC-FID of the filtered oils allowed to understand the efficacy of filtration. Most of the particulate contamination was removed by filtration leading to a reduction from 69 mg/L in the unfiltered sample to < 2 mg/L in the filtered samples. Particle characterization confirmed that the main contamination is composed of iron, calcium and silicon-based contaminants in combination with carbon-based species. It was confirmed by ICP-OES that after filtration, important contaminants such as nickel, vanadium and lead were reduced below contamination thresholds for steam crackers indicating that filtration is an efficient, and potentially cost-effective upgrading technique for pyrolysis oils. When steam cracking the filtered oils, results show that radiant coil coke formation was reduced by 40–60% compared to the unfiltered oil without changes in product selectivity, confirming the strong impact of particulate contamination on coke formation during steam cracking.

Evaluation of a single-use disk stack centrifuge for improved efficiency and sustainability at 1000 L GMP manufacturing scale.

Direct depth filtration is an established technology for single-use harvest operation. Advantages of direct depth filtration include familiarity with depth filtration in downstream processes and simplicity of the operation. Drawbacks include low capacity, large footprint, labor-intensive set-up, high water use, and high waste in the form of discarded filters. Single-use centrifugation is emerging as an alternative to depth filtration for the single-use harvest step. Within the single-use centrifugation space, disc stack centrifugation represents the newest entrant. In this study, we evaluated the performance of the GEA kytero single-use disc stack centrifuge to clarify two monoclonal antibody-producing cell culture fluids. The separation performance of the GEA kytero centrifuge varied between the two cell culture fluids, with differences in centrate turbidity and centrate filterability measured. A comparison was then performed to determine resource savings, compared to direct two-stage depth filtration, when using a GEA kytero centrifuge to harvest a 1000 L bioreactor. The analysis concluded that replacement of the first stage of depth filters with a GEA kytero centrifuge has the potential to decrease the required second stage depth filtration area by up to 80%. The decrease in depth filter area resulting from the use of the GEA kytero would result in a decrease in the harvest step footprint, a decrease in buffer volume required to prime and rinse depth filters, and a decrease in the volume of plastic waste. An economic comparison of the GEA kytero single-use centrifuge against a direct depth filtration step found that for a 1000 L harvest step, the GEA kytero centrifuge may reduce costs by up to 20% compared with two-stage direct depth filtration.