Depth Filtration Research Articles

Feasibility of membrane ultrafiltration as a single-step clarification and fractionation of microalgal protein hydrolysates.

Protein hydrolysates are one of the most valuable products that can be obtained from lipid-extracted microalgae (LEA). The advantages of protein hydrolysates over other protein products encompass enhanced solubility, digestibility, and potential bioactivity. The development of an economically feasible process to produce protein hydrolysates depends on maximizing the recovery of hydrolyzed native protein from the lipid-extracted algal biomass and subsequent fractionation of hydrolyzed protein slurry. Previously, we reported a method for fractionation of enzymatically generated protein hydrolysates by acidic precipitation of algal cell debris and unhydrolyzed protein, precipitate wash, centrifugation, and depth filtration. The present study evaluates tangential flow ultrafiltration as a single-step alternative to centrifugation, precipitate wash, and depth filtration. The results demonstrate that the tangential flow ultrafiltration process has a potential that deserves further investigation. First, the membrane diafiltration process uses a single and easily scalable unit operation (tangential flow filtration) to separate and “wash out” hydrolyzed protein from the algal residue. Second, the protein recovery yield achieved with the tangential flow process was >70% compared to 64% previously achieved by centrifugation and depth filtration methods. Finally, protein hydrolysates obtained by membrane ultrafiltration exhibited slightly better heat and pH stability.

Membrane Chromatography-Based Downstream Processing for Cell-Culture Produced Influenza Vaccines.

New influenza strains are constantly emerging, causing seasonal epidemics and raising concerns to the risk of a new global pandemic. Since vaccination is an effective method to prevent the spread of the disease and reduce its severity, the development of robust bioprocesses for producing pandemic influenza vaccines is exceptionally important. Herein, a membrane chromatography-based downstream processing platform with a demonstrated industrial application potential was established. Cell culture-derived influenza virus H1N1/A/PR/8/34 was harvested from benchtop bioreactor cultures. For the clarification of the cell culture broth, a depth filtration was selected as an alternative to centrifugation. After inactivation, an anion exchange chromatography membrane was used for viral capture and further processing. Additionally, two pandemic influenza virus strains, the H7N9 subtype of the A/Anhui/1/2013 and H3N2/A/Hong Kong/8/64, were successfully processed through similar downstream process steps establishing optimized process parameters. Overall, 41.3–62.5% viral recovery was achieved, with the removal of 86.3–96.5% host cell DNA and 95.5–99.7% of proteins. The proposed membrane chromatography purification is a scalable and generic method for the processing of different influenza strains and is a promising alternative to the current industrial purification of influenza vaccines based on ultracentrifugation methodologies.

Optimal dosage strategies for filter aid filtration processes with compressible cakes

We establish optimal time-dependent dosage strategies for compressible filter aid materials, focusing on dead-end filter aid filtration processes operated in constant flow mode. To this end, we apply a direct optimal control approach by repeatedly evaluating a mathematical filtration model with filter aid concentration as the unknown time-dependent control function. Our algorithm iteratively constructs the sought-for trajectory to minimize a cost functional representing previously defined performance goals. We evaluate our optimal control approach for two different model formulations. In the first one, all impurity particles are separated by pure surface filtration on top of the existing filter cake, whereas in the second one, the model is extended toward depth filtration in the filter cake. Particularly for the latter, optimally controlled dosage strategies yield a significant performance improvement of up to 30% reduced filter aid consumption compared with the already optimized but constant filter aid dosage.

Milliscale reactors for integration of continuous precipitation and filtration

AbstractBACKGROUNDThe development of integrated continuous biomanufacturing processes faces a significant challenge when the parameters for the design of the process cannot be accurately estimated from those of batch experiments. Process design is even more challenging if the outcome of one unit operation highly influences the performance of the subsequent one, such as in harvesting of a precipitate by filtration. In the case of protein precipitation, results from the batch and continuous experiements deviate and their scale‐down is limited. Microfluidics suffer from poor mixing characteristics. Thus, milliscale devices were developed to maintain mixing performance but at the expense of a slightly larger scale.RESULTSMilliscale devices were developed for the precipitation of antibodies in continuous tubular reactors to compare different dosage times in small scale. The reactors have multiple addition points for precipitant for the continuous, controlled and precise addition of the precipitating agent without valves. The designed devices have a narrow residence time distribution to achieve fast mixing and a small volume that reduces the time and cost for experiments tenfold. Milliscale devices were used to evaluate the most appropriate dosage time for protein precipitation, thus improving purity by a factor of 3 compared to single addition. The resulting filterability of precipitates in tangential flow filtration and depth filtration was improved.CONCLUSIONResults demonstrated that multiple additions were more beneficial than single addition because they help to reduce pressure and increase filter capacity. Such devices can be used to determine and adjust the precipitation methodology to optimize floc formation and improve solid–liquid separation while reducing development time and cost. © 2022 The Authors. Journal of Chemical Technology and Biotechnology published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry (SCI).

Asymmetric depth-filtration: A versatile and scalable method for high-yield isolation of extracellular vesicles with low contamination.

We developed a novel asymmetric depth filtration (DF) approach to isolate extracellular vesicles (EVs) from biological fluids that outperforms ultracentrifugation and size‐exclusion chromatography in purity and yield of isolated EVs. By these metrics, a single‐step DF matches or exceeds the performance of multistep protocols with dedicated purification procedures in the isolation of plasma EVs. We demonstrate the selective transit and capture of biological nanoparticles in asymmetric pores by size and elasticity, low surface binding to the filtration medium, and the ability to cleanse EVs held by the filter before their recovery with the reversed flow all contribute to the achieved purity and yield of preparations. We further demonstrate the method's versatility by applying it to isolate EVs from different biofluids (plasma, urine, and cell culture growth medium). The DF workflow is simple, fast, and inexpensive. Only standard laboratory equipment is required for its implementation, making DF suitable for low‐resource and point‐of‐use locations. The method may be used for EV isolation from small biological samples in diagnostic and treatment guidance applications. It can also be scaled up to harvest therapeutic EVs from large volumes of cell culture medium.

UAV Based Indoor Localization and Objection Detection.

This article targets fast indoor positioning and 3D target detection for unmanned aerial vehicle (UAV) real-time task implementation. With the combined direct method and feature method, a method is proposed for fast and accurate position estimation of the UAV. The camera pose is estimated by the visual odometer via the photometric error between the frames. Then the ORB features can be extended from the keyframes for the map consistency improvement by Bundle Adjustment with local and global optimization. A depth filter is also applied to assist the convergence of the map points with depth information updates from multiple frames. Moreover, the convolutional neural network is used to detect the specific target in an unknown space, while YOLOv3 is applied to obtain the semantic information of the target in the images. Thus, the spatial map points of the feature in the keyframes can be associated with the target detection box, while the statistical outlier filter can be simultaneously applied to eliminate the noise points. Experiments with public dataset, and field experiments on the established UAV platform in indoor environments have been carried out for visual based fast localization and object detection in real-time for the efficacy verification of the proposed method.

The influence of filtration velocity on the full-sized fibrous filter performance

Filtration velocity is a fundamental parameter that influences fibrous filtration performance. The previous work focuses on the effect of velocity on filtration performance, mainly using downsized filters, a flat sheet media or numerical methods. In this study, the actual performance of the full-sized fibrous filters was simulated according to standard test procedures, ISO 16890:2016 at different filtration velocities. The experimental findings show that the filtration efficiency increases with increasing velocity as the inertial impaction increases at higher velocity. The initial pressure differential shows an increasing relationship at [Formula: see text] with increasing velocity. The dust cake specific resistance coefficient, K c increases linearly with the velocity at the depth filtration stage and the beginning of transitional filtration stage. K c exhibits a quadratic growth with filtration velocity since the middle stage of transitional filtration and surface filtration. Dust holding capacity would be reduced and the final pressure differential would be increased with the increasing velocity due to the greater force incurred by the higher velocity, causing the filter media to deform and rupture easily. The experimental outcome of this study can be applied directly to industrial and commercial heating, ventilation and air conditioning design in consideration of the filter pressure differential for a lower energy consumption without compromising the efficiency for indoor air quality.

Predictive modelling of a rapid stratified bed filter for turbidity removal from surface water

The objective of the present work was to evaluate the hydrodynamic behaviour of a stratified bed filtration column consisting of 4 cm of sand and 2 cm of limestone to remove turbidity and measuring the head loss through the filter in several runs. In this study, two types of sand were used as filtering bed material, one fine and one medium. Crushed limestone was also available. These materials were characterized to determine the average particle diameter, porosity, and permeability coefficient. These were respectively 1.7∙10 –4 m, 336.96 and 0.68 m∙day –1 for fine sand, 3.3∙10 –4 m, 654.24 and 2.59 m∙day –1 for the medium sand and 1.26∙10–3 m, 388.8 and 8.64 m∙day–1 for crushed limestone. Using these materials, hydrodynamic analyses were carried out using clean water under rapid filtration conditions. In these analyses, different filtration rates were determined to be used in each experiment. Once the filtration rates were determined, the filtration analysis was performed with synthetic turbid water prepared at 8 NTU using tap water and bentonite. From the results obtained, a predictive model was developed based on total head losses for the evaluated filter, maintaining the rapid filtration condition. As a result, a turbidity removal efficiency of 97.7% was obtained with a total head loss of 17.8 cm at a filtration rate of 153 m·day –1. The developed model predicted head loss as a function of operating time, filtration rate, and filter depth to maximise turbidity removal. The model showed excellent prediction accuracy with R2 of 0.9999, which indicates that the model predictions are not biased. It was concluded that, due to the porosity of these materials, a stratified bed of sedimentary rocks has a great potential to be used in surface water filtration processes, which implies that it could be used at the rural community level as a form of water treatment, since the

Optimum design of a recharge filter for recharging the dug wells: a field application

Artificial recharging of the abandoned and/or functional dug wells through a recharge filter is an efficient and economical method for mitigating and maintaining depleting water tables. An optimum sizing of the recharge filter is necessary to avoid its over-design or under-design and has a minimum cost. Optimum sizing of the recharge filter for the dug well recharging has received very little attention, especially in India. In this paper, analytical expressions for designing the recharge filter were derived based on the concept of maximization of the hydrological water balance equation. Optimum sizing of the recharge filter based on the minimum cost was formulated using the optimization model. The optimization model was solved using the Snopt non-linear programming optimization model of the AMPL software. The results of the optimization model were also compared with the analytical framework. Sensitivity analyses using an analytical framework indicated that size, time of filling and empty time for the recharge filter were more sensitive to the changes in watershed area and watershed condition as compared to the diameter of the discharge pipe, the porosity of the filter material and depth of the recharge filter. It could be concluded that the derived optimization model incorporating the derived analytical expressions can successfully be used for optimum sizing and evaluation of the effectiveness of the recharge filter of any shape and locations in different hydro-climatic regions.

Production of Lentiviral Vectors Using a HEK-293 Producer Cell Line and Advanced Perfusion Processing.

The field of lentiviral vector (LV) production continues to face challenges in large-scale manufacturing, specifically regarding producing enough vectors to meet the demand for treating patients as well as producing high and consistent quality of vectors for efficient dosing. Two areas of interest are the use of stable producer cell lines, which facilitates the scalability of LV production processes as well as making the process more reproducible and robust for clinical applications, and the search of a cell retention device scalable to industrial-size bioreactors. This manuscript investigates a stable producer cell line for producing LVs with GFP as the transgene at shake flask scale and demonstrates LV production at 3L bioreactor scale using the Tangential Flow Depth Filtration (TFDF) as a cell retention device in perfusion mode. Cumulative functional yields of 3.3 x 1011 and 3.9 x 1011 transducing units were achieved; the former over 6 days of LV production with 16.3 L of perfused media and the latter over 4 days with 16 L. In comparing to a previously published value that was achieved using the same stable producer cell line and the acoustic filter as the perfusion device at the same bioreactor scale, the TFDF perfusion run produced 1.5-fold higher cumulative functional yield. Given its scale-up potential, the TFDF is an excellent candidate to be further evaluated to determine optimized conditions that can ultimately support continuous manufacturing of LVs at large scale.

Monocular 3D object detection with Pseudo-LiDAR confidence sampling and hierarchical geometric feature extraction in 6G network

The high bandwidth and low latency of 6G network technology enable the successful application of monocular 3D object detection on vehicle platforms. Monocular 3D-object-detection-based Pseudo-LiDAR is a low-cost, low-power solution compared to LiDAR solutions in the field of autonomous driving. However, this technique has some problems, i.e., (1) the poor quality of generated Pseudo-LiDAR point clouds resulting from the nonlinear error distribution of monocular depth estimation and (2) the weak representation capability of point cloud features due to the neglected global geometric structure features of point clouds existing in LiDAR-based 3D detection networks. Therefore, we proposed a Pseudo-LiDAR confidence sampling strategy and a hierarchical geometric feature extraction module for monocular 3D object detection. We first designed a point cloud confidence sampling strategy based on a 3D Gaussian distribution to assign small confidence to the points with great error in depth estimation and filter them out according to the confidence. Then, we present a hierarchical geometric feature extraction module by aggregating the local neighborhood features and a dual transformer to capture the global geometric features in the point cloud. Finally, our detection framework is based on Point-Voxel-RCNN (PV-RCNN) with high-quality Pseudo-LiDAR and enriched geometric features as input. From the experimental results, our method achieves satisfactory results in monocular 3D object detection.

Numerical Simulation of Particle-Laden Flow and Soot Layer Formation in Porous Filter

So far, diesel particulate filters (DPFs) have been widely used to collect diesel particulates including soot in the exhaust after-treatment. However, as the soot is continuously collected in the porous filter, the exhaust pressure (pressure drop) increases. To optimize the filter design for reducing its pressure drop, we need a numerical simulation. In this study, we simulated the particle-laden flow across the DPF. Structure of SiC-DPF was obtained by an X-ray CT technique. We conducted the numerical simulation by changing the soot aggregation diameter (simply called soot size), and evaluated the time-variation of the pressure drop. For discussing the soot deposition process, the contributions of the Brownian diffusion and the interception effect were separately estimated. Especially, we focused on the soot deposition region which could affect the pressure drop, together with the soot cake permeability and the soot packing density. Results show that, as the soot size is smaller, more soot is trapped. As a result, the shift from the depth filtration to the surface filtration is observed earlier. Therefore, for discussing the pressure drop, it is important to consider where the soot deposition occurs as well as the deposited soot mass in the filter.

Clarification of recombinant adeno-associated virus (rAAV) & lentivirus from adherent culture

In recent years the cell and gene therapy industries have been rapidly expanding, with two of the most utilized viral vector classes being adeno-associated virus (AAV) and lentivirus. With clinical success comes the need to develop and scale-up efficient manufacturing processes. As both of these vectors are produced in cells, the first step in their purification is to clarify them from the cell culture. There are many technologies traditionally used for cell culture clarification but given the projected manufacturing scales and need for single-use consumables a combination of depth and membrane filtration is a logical fit for batch processing of viral vectors. This work focuses on developing filtration-based clarification processes for both AAV and lentivirus. The data shows robust turbidity reduction and step yields across batches, scales, and AAV serotypes. We discuss how capacity can be impacted by feedstream characteristics and how capacities translate to manufacturing footprints. Finally, we discuss some process considerations that are unique to viral vector processing and critical to successful vector harvest.

An innovative strategy to recycle permeate in biologics continuous manufacturing process to improve material efficiency and sustainability.

Intensified perfusion processes are an integral part of continuous manufacturing for biopharmaceuticals which enable agile operations and significant reduction in cost of goods. However, they require large volumes of media to support robust cell growth and maintain high productivity, posing substantial challenges to operations, logistics, and process sustainability. This study explores a novel strategy for reprocessing and reusing permeate from perfusion cultures for mAb production. The concept was initially evaluated by recycling permeate, Protein A flow-through (ProA FT) and CEX processed ProA FT in deep-well plate mock perfusion and ambr® 250 perfusion formats. Further processing of ProA FT through a cation exchange depth filter before recycling reduced process impurities such as host cell proteins (HCPs) and DNA. However, a direct replacement of fresh media with spent media reduces nutrient depth which results in a concomitant reduction in productivity. In ambr® 250 bioreactors, recycling of ProA FT at 25%-50% replacement rates (defined as the fraction of recycled material in media) resulted in a 13%-30% reduction in cumulative productivity while maintaining product quality. To mitigate this, we used media concentrates which allowed independent modulation of media depth by replacing a portion of diluent WFI with recycled material. Results from deep-well mock perfusion studies demonstrated that comparable or higher productivities relative to control can be achieved with this approach. Taken together, our study demonstrates the feasibility of recycling permeate in perfusion cultures. Process mass intensity (PMI) calculations reveal that this approach can meaningfully improve material efficiency by reducing water consumption, thereby enhancing overall bioprocess sustainability.

Digital Twin for HIV-Gag VLP Production in HEK293 Cells

The development and adoption of digital twins (DT) for Quality-by-Design (QbD)-based processes with flexible operating points within a proven acceptable range (PAR) and automation through Advanced Process Control (APC) with Process Analytical Technology (PAT) instead of conventional process execution based on offline analytics and inflexible process set points is one of the great challenges in modern biotechnology. Virus-like particles (VLPs) are part of a line of innovative drug substances (DS). VLPs, especially those based on human immunodeficiency virus (HIV), HIV-1 Gag VLPs, have very high potential as a versatile vaccination platform, allowing for pseudotyping with heterologous envelope proteins, e.g., the S protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). As enveloped VLPs, optimal process control with minimal hold times is essential. This study demonstrates, for the first time, the use of a digital twin for the overall production process of HIV-1 Gag VLPs from cultivation, clarification, and purification to lyophilization. The accuracy of the digital twins is in the range of 0.8 to 1.4% in depth filtration (DF) and 4.6 to 5.2% in ultrafiltration/diafiltration (UFDF). The uncertainty due to variability in the model parameter determination is less than 4.5% (DF) and less than 3.8% (UFDF). In the DF, a prediction of the final filter capacity was demonstrated from as low as 5.8% (9mbar) of the final transmembrane pressure (TMP). The scale-up based on DT in chromatography shows optimization potential in productivity up to a factor of 2. The schedule based on DT and PAT for APC has been compared to conventional process control, and hold-time and process duration reductions by a factor of 2 have been achieved. This work lays the foundation for the short-term validation of the DT and PAT for APC in an automated S7 process environment and the conversion from batch to continuous production.

Removal of MS2 and fr Bacteriophages Using MgAl2O4-Modified, Al2O3-Stabilized Porous Ceramic Granules for Drinking Water Treatment.

Point-of-use ceramic filters are one of the strategies to address problems associated with waterborne diseases to remove harmful microorganisms in water sources prior to its consumption. In this study, development of adsorption-based ceramic depth filters composed of alumina platelets was achieved using spray granulation (calcined at 800 °C). Their virus retention performance was assessed using cartridges containing granular material (4 g) with two virus surrogates: MS2 and fr bacteriophages. Both materials showed complete removal, with a 7 log10 reduction value (LRV) of MS2 up to 1 L. MgAl2O4-modified Al2O3 granules possessed a higher MS2 retention capacity, contrary to the shortcomings of retention limits in pure Al2O3 granules. No significant decline in the retention of fr occurred during filtration tests up to 2 L. The phase composition and morphology of the materials were preserved during filtration, with no magnesium or aluminum leakage during filtration, as confirmed by X-ray diffractograms, electron micrographs, and inductively coupled plasma-optical emission spectrometry. The proposed MgAl2O4-modified Al2O3 granular ceramic filter materials offer high virus retention, achieving the criterion for virus filtration as required by the World Health Organization (LRV ≥ 4). Owing to their high thermal and chemical stability, the developed materials are thus suitable for thermal and chemical-free regeneration treatments.

Insights From the Analysis of Clinicopathological and Prognostic Factors in Patients With Gallbladder Cancer.

AimsTo investigate the clinical efficacy and prognostic factors of primary gallbladder cancer (GBC) treated by radical surgery.MethodsThe clinical and pathological data of 168 patients with primary gallbladder cancer admitted and treated in the Third Affiliated Hospital of Soochow University from January 1st, 2010 to December 31st, 2018 were analyzed retrospectively. Kaplan Meier method was used to draw the survival curve and evaluate the survival rate. Chi-square test was used for univariate analysis and binary logistic regression was used for multivariate analysis.Results94 cases showed symptoms of abdominal pain and abdominal distension. 7 cases showed symptoms of fatigue and weight loss. Jaundice occurred in 10 patients. Fever occurred in 6 patients. 51 patients had no symptoms at all. The median survival time of 168 patients was 35.0 (1.0 ~ 142.0) months. The overall 1-, 2- and 3-year cumulative survival rates were 69.6%, 55.4% and 48.8% respectively. The univariate analysis indicated that preoperative bilirubin, tumor size, tumor location, pathological type, degree of differentiation, liver invasion, nerve invasion, vascular invasion, surgical margin, filtration depth and N staging were significant factors influencing prognosis of patients with primary GBC (P<0.05). The results of multivariate analysis demonstrated that degree of differentiation, nerve invasion, filtration depth and N staging were independent risk factors for prognosis of patients with primary GBC (P<0.05).ConclusionPatients with risk factors of gallbladder cancer should be more active in early cholecystectomy to avoid the malignant transformation of benign diseases. Degree of differentiation, nerve invasion, filtration depth and N staging were important factors for poor prognosis of patients with primary GBC. For T4 staging patients, preoperative evaluation should be more comprehensive, and patients and surgeons should be more prudent in adopting appropriate clinical treatment. The primary purpose should be prolonging the survival time and improving the quality of life.

Laboratory assessment of media clogging in bioretention systems: Effects of sawdust addition, plant species and dry-wet alternation

Bioretention system has received increasing attention as a more natural approach to stormwater management, while clogging is recognized as the main limiting factor in its long-term operation. In this study, a laboratory-scale bioretention systems were constructed to investigate the influence of different factors on the media clogging. The addition of sawdust in filter media (sand and sandy loam soil mixture) had no obvious effect on suspended solids (SS) accumulation and matrix porosity in different depth of filter, but effectively increased the hydraulic conductivity of bioretention systems. Similarly, there was also no significant difference in spatial or temporal variations in SS accumulation between three systems with different plants (p > 0.05). Nevertheless, plant species had significant influence on the hydraulic conductivity, with Acorus calamus L. demonstrating to be appropriate to mitigating the clogging (p < 0.05). Dry-wet alternation helped to improve the hydraulic performance. The results showed that the upper layer (0–20 cm) was more prone to clogging while dry period was conductive to alleviating media clogging no matter in summer or winter rainfall mode. This study will contribute to a greater understanding of the hydraulic performance and provide guidance for alleviating media clogging in bioretention systems.

Role of biological granular activated carbon in contaminant removal and ultrafiltration membrane performance in a full-scale system

This study evaluated a long-term impact of biological activated carbon (BAC) filter that was employed in a full-scale drinking water treatment plant to enhance the removal of contaminants by the ultrafiltration (UF) process. The results showed that BAC enhanced UF performance by increasing the flux by 18.5% and extending the filtration run by 45%. The presence of BAC improved the removal of primary contaminants, including dissolved organic carbon (4–40%), UV 254 (10–57.7%), geosmin and 2-methylisoborneol (80%). BAC was also effective in decreasing the concentration of biopolymers, humic substances, (semi-)volatile organics, chlorite and halonitromethanes, thereby lowering contaminant load on the UF unit. The changes in primary water quality parameters in the combined process showed that the humic substances in dissolved organic nitrogen, low molecular weight substances in UV 254 , and fluorescence protein-like substances could be useful indicators for DBPs as these organic fractions had strong correlation with DBPs. Obvious spatio-temporal characteristics of GAC grain and microbial communities in BAC filter were observed with operation time and filter depth. The bacterial community in BAC filter was highly diverse and was less influenced by influent quality with an increase in filter depth, while the communities in UF cake layer correlated with organic removal in the UF system. • The BAC performance in a hybrid full-scale DWTP in combination with UF was studied. • BAC could increase the UF flux by 18.5% and extend the filtration run by 45%. • BAC removed 4–40% of DOC, 10–57.7% of UV 254 and 80% of 2- MIB in sand filtrate. • BAC was more effective in controlling N-DBPFP than C-DBPFP, in particular for HNMs. • The microbial communities in BAC filter exhibited temporal and spatial variability.

Scale-up issues for commercial depth filters in bioprocessing.

Significant increases in cell density and product titer have led to renewed interest in the application of depth filtration for initial clarification of cell culture fluid in antibody production. The performance of these depth filters will depend on the local pressure and velocity distribution within the filter capsule, but these are very difficult to probe experimentally, leading to challenges in both process design and scale-up. We have used a combination of carefully designed experimental studies and computational fluid dynamics (CFD) to examine these issues in both lab-scale (SupracapTM 50) and pilot-scale (StaxTM ) depth filter modules, both employing dual-layer lenticular PDH4 media containing diatomaceous earth. The SupracapTM 50 showed a more rapid increase in transmembrane pressure and a more rapid DNA breakthrough during filtration of a Chinese Hamster Ovary cell culture fluid. These results were explained using CFD calculations which showed very different flow distributions within the modules. CFD predictions were further validated using measurements of the residence time distribution and dye binding in both the lab-scale and pilot-plant modules. These results provide important insights into the factors controlling the performance and scale-up of these commercially important depth filters as well as a framework that can be broadly applied to develop more effective depth filters and depth filtration processes.