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A fibrous filter is a common cleaning device often used to remove particles from industrial gas streams. The main question which often arises concerns the evolution of the pressure drop and the filtration efficiency during the filter clogging. In the present study, the loading characteristics of HEPA filters have been studied experimentally. The increase of pressure drop and filter efficiency was measured and was linked to both the penetration profile inside the filter bed and the deposit structure observed thanks to scanning electron micrograph. We have also studied the influence of various parameters such as air velocity, particle size, aerosol concentration and filter main characteristics. A depth and surface filtration model has been developed based on the distinction between the fibres of the filter and deposited particles resulting in additional fibres inside the filter or on the filter surface. We can notice a good agreement between model and experiment. Moreover, model very well describes the transition area between depth filtration and cake filtration. This transition from one type of filtration to another is a continuous process. Model describes also the exponential decrease of penetration profile.

Twenty-five representative water treatment plants were surveyed to compare differences in microbial, physical, and chemical water quality of raw waters and spent filter backwash waters (SFBWs). On the basis of the observed Giardia and Cryptosporidium levels, it was determined that a recycle ratio of 5-10% would be sufficient to minimize the impact of protozoa on ambient raw water. Using the cell culture-polymerase chain reaction method, infectious Cryptosporidium oocysts were observed in raw water and SFBW samples. The presence of particles in the SFBW samples increased the potassium permanganate demand by a factor of 5.5 and the chlorine dioxide demand by a factor of 4.0. However, the presence of particles in SFBWs did not affect the inactivation of Cryptosporidium. Conventional treatment of SFBW with polymers resulted in excellent removal of turbidity, particles, and microorganisms. A backwashable depth filter can be used in place of a conventional filter for control of Cryptosporidium in clarified SFBW.

Despite recent developments in bottom-up proteomics, the need still exists in a fast, uncomplicated, and robust method for comprehensive sample processing especially when applied to low protein amounts. The suspension trapping method combines the advantage of efficient SDS-based protein extraction with rapid detergent removal, reactor-type protein digestion, and peptide cleanup. Proteins are solubilized in SDS. The sample is acidified and introduced into the suspension trapping tip incorporating the depth filter and hydrophobic compartments, filled with the neutral pH methanolic solution. The instantly formed fine protein suspension is trapped in the depth filter stack-this crucial step is aimed at separating the particulate matter in space. SDS and other contaminants are removed in the flow-through, and a protease is introduced. Following the digestion, the peptides are cleaned up using the tip's hydrophobic part. The methodology allows processing of protein loads down to the low microgram/submicrogram levels. The detergent removal takes about 5 min, whereas the tryptic proteolysis of a cellular lysate is complete in as little as 30 min. We have successfully utilized the method for analysis of cellular lysates, enriched membrane preparations, and immunoprecipitates. We expect that due to its robustness and simplicity, the method will become an essential proteomics tool.

Intermittent and hitherto inexplicable blinding of depth filters have been experienced during the large-scale primary downstream processing of mammalian cell culture broths. Distinct populations of either healthy viable mammalian cells or those that had suffered cell death via apoptosis or necrosis were assessed for their ability to impact on the resistance of a depth filter of a type that is commonly used to remove cells in bioprocesses. Apoptotic and necrotic cells were found to induce a pressure drop 1.7 and 15.0 times greater than the corresponding pressure drop induced by viable cultures, respectively. There were no apparent explanations for this in terms of the size distribution of debris and cells. However, DNA removed from the cell culture supernatant was separated electrophoretically and the necrotic culture was clearly identified as containing chiefiy high molecular weight DNA, whereas the supernatant of viable and apoptotic cultures contained low molecular weight DNA. Further treatment of necrotic cultures with DNase 1 or benzonase resulted in these cultures having a reduced impact on the resistance of the depth filter, as compared with untreated necrotic cultures. The significance of high molecular weight DNA in the filtration of biological materials was clearly indicated.

Two 30 urn tortuous path depth filters, associated with either a magnetic or non‐magnetic, but otherwise identical, fuel treatment device were placed in a tandem recirculating fuel oil system comprising a single reservoir of fuel oil (red diesel) contaminated with seawater and fuel degrading microbes. For 17 d the recirculating system, with no added mixing of the reservoir, showed no significant decrease in performance (measured through volume flux). On perturbation and constant gentle mixing of the reservoir thereafter, the volume flux after the filter associated with the magnetic device decreased linearly over the next 18 d to ca 65% of its initial stable value. The volume flux after the filter with the non‐magnetic device decreased much more quickly to around 25% of its initial stable value. The rate of reduction in volume flux after the non‐magnetic device appeared to increase with time. Both filters were being blocked but the one associated with the magnetic device did so at a significantly slower ra...

Column filtration experiments with 2 mm- Φ glass beads were conducted to investigate the behavior of colloids during filtration. Algae and kaolin were used as model particles, while the chemical system was altered by changing the electrolyte concentration and pH. The collision efficiencies from the interaction between colloids and the filter medium were calculated with a semi-empirical approach of the single sphere model and clean-bed filtration theory. The experimental results indicate that ionic strength enhance the removal efficiencies for both algae and kaolin particles significantly. The removal efficiency of the filter for algae decreased with the increase in pH for up to pH 6. No significant change was observed beyond pH 6. Removal efficiencies for kaolin decreased with an increase in pH. It is concluded that collision efficiencies are sensitive to ion strength and pH.

The physical parameters governing adsorption of DNA by various positively charged depth filters and membranes have been assessed. Buffers that reduced or neutralised the depth filter or membrane charge, and those that impeded hydrophobic interactions were shown to affect their operational capacity, demonstrating that DNA was adsorbed by a combination of electrostatic and hydrophobic interactions. The adsorption profile of DNA by a Sartobind Q anion exchange membrane showed immediate breakthrough, irrespective of challenge DNA concentration or flow rate, and in this case adsorption was by electrostatic interactions only. The production-scale removal of DNA from harvest broths containing therapeutic protein by partitioning of cells and debris from protein in sequential centrifugation and filtration steps, and the concentration of DNA in process supernatant were assessed. Centrifugation reduced the quantity of DNA in the process material from 79.8 μg ml-1 to 9.3 μg ml-1 whereas the concentration of DNA in the supernatant of pre- and post-filtration samples had only marginally reduced DNA content: from 6.3 to 6.0 μg ml-1 respectively. DNA was concentrated to 27.3 μg ml-1 along with monoclonal antibody in the ultrafiltration step. Similar effects were observed in the harvest step for a second antibody.

This paper describes two assessment methods for UF type of membranes for large-scale applications. The combination of those two methods results in quite clear and unambiguous answers to the question what membranes are of interest for long-term testing. With the first method, called dead-end filtration method, information is generated on the suitability of the membrane and on the combination of the membrane material, the module hydraulics and assembly. With this method the evolution of TMP is monitored upon filtration cycles of 20 minutes with raw water at a flux rate of 120 l/h.m 2 , alternated with backwash cycles with permeate of 40 seconds at 1.2 bar negative TMP. The second method, called cross-flow filtration method, gives exclusively information on the suitability of the membrane material. This is being done by the measurement of the absolute value of the so-called plateau fluxes in cross-flow mode at 0.2 m/s linear velocity. For this purpose raw water concentrates are being used. Three open UF type of membranes, all three in hollow fibre configuration were assessed with these two methods. It was shown that the PSf based membrane (Koch PM100) reached already after 4 filtration cycles a TMP of 1 bar and showed the lowest plateau flux (25 l/h.m 2 ). This indicated that the membrane suffered from interaction with the raw water. Moreover, it is possible that something was wrong with the hydraulics of this membrane. The two other membranes were PES/PVP based. These membranes showed much less TMP increase over time. The first membrane of this type was X-Flow UFC, the second Stork Friesland Superfil 015-010. It was no problem to operate the first membrane for 18 hours without addition of chemicals for cleaning. The second membrane reached the maximum allowed TMP of 1 bar after 16 hours of operation at the end of the filtration cycle. Moreover, for both membranes a higher plateau flux value (35 l/h.m 2 ) was found. Both observations indicate that this type of membrane material is much more interesting than PSf. It was also shown that the X-Flow membrane gives the lowest absolute TMP values, which is attributed to its higher pure water permeability (740 l/h.m 2 .bar) as compared to the Stork Friesland membrane (pure water permeability of 350 l/h.m 2 .bar) and the Koch membrane (pure water permeability of 290 l/h.m 2 .bar). A last observation was a TMP increase of only 0.1 bar per cycle for the X-Flow membrane, as compared to 0.2 bar for the two others. This observation is in agreement with earlier made FESEM pictures of the inner surfaces. This means that the X-Flow membrane rather acts as a depth filter, whereas the two other membranes act as a surface filter.

The molecular weight of DNA from a large-scale, fed-batch, mammalian cell culture vessel has been evaluated as process material passes through the initial stages of a purification scheme for monoclonal antibodies. High molecular weight DNA was substantially cleared from the broth after passage through a disc stack centrifuge and the remaining low molecular weight DNA was largely unaffected by passage through a series of depth filters and a sterilising grade membrane. Removal of high molecular weight DNA was shown to be coupled with clarification of the process stream. The DNA from cell culture supernatant showed a pattern of internucleosomal cleavage of chromatin when fractionated by electrophoresis but the presence of both necrotic and apoptotic cells throughout the fermentation meant that the origin of the fragmented DNA could not be unequivocally determined.

Periodically regenerateable cake-forming filters have assumed a commercially dominant role in air purification because of their excellent dust collection capabilities. However intensive experimental investigations are usually necessary to optimally design such filters due to the absence of calculation models. In this work an extended computer simulation model is presented, which is capable of simulating the whole filtration (an alternate succession of filtration and regeneration of the filter medium). With this model the long-term behaviour of such a filter was examined and it was found that the compressibility of the dust has a major influence on the operation costs: The more compressible a dust is the sooner the filter has to be replaced due to particles inside the filter medium which cannot be removed anymore.

Periodically regenerable cake-forming filters have assumed a commercially dominant role in air purification due to their excellent dust collection capabilities. These filters are used to separate particles from gases with high dust concentrations, whereby the separation arises as the dust-gas mixture passes through the filter medium and the particles are retained. As soon as a certain maximum pressure drop over the filter medium is reached the filter medium is regenerated. In order to optimally design such filters, there are three important parameters for the economical evaluation of the filter: the correlating pressure drop increase of the filter during filtration which is mainly influenced by the compressibility of the dust cake, the dust separation efficiency especially at the beginning of the filtration and the rise of the residual pressure drop of the filter after several cycles of filtration and regeneration. In this work a 2-dimensional computer simulation model for the compressible dust cake build-up on widely used non-woven fabrics (needle-felts) is introduced. First this model is used to investigate the mechanism causing compression inside dust filter cakes and to clarify different compression phenomena. Second it is shown that this simulation program is capable of describing the particle penetration inside and through the filter medium, the clogging of the filter medium and the growing of the dust filter cake out of the filter medium, whereby the corresponding pressure drop and the number of particles in the clean gas as an function of the filtration time show good qualitative agreement with known experimental data.

Sartorius' Mahesh Prashad and Klaus Tarrach look at the current and future use of cellulose-based depth filter technologies, in the initial recovery processes of biopharmaceuticals manufacturing.

Researchers have studied various types of respirable dust sampling filters to determine if the differential pressure across them at a constant air flow rate can be used to estimate the accumulated dust mass. Results suggest that glass fiber depth filters that allow the dust particles to penetrate well into the filter material have considerable merit. The correlation between the increase in differential pressure (AP) and dust mass (M) when using 37-mm glass fiber filters is linear, provided they are not loaded with more than approximately 5 mg of dust. Under these conditions, the relationship between differential pressure and dust mass can be described by the equation [°P(cm H2O) = 0.25 M(mg)]. Most of the data fall within ± 25 percent of a best-fit regression line and have a correlation coefficient (R2) of 0.88. These results were obtained using coal dusts from Pittsburgh, Upper Freeport, and Pocahontas seams mixed with various percentages (0 to 100%) of rock dust. The density of these dusts vari...

The monoclonal-antibody production of an immobilized hybridoma cell line cultivated in a fluidized-bed reactor was monitored on-line for nearly 900 h. The monoclonal antibody concentration was determined by an immuno affinity-chromatography method (ABICAP). Antibodies directed against the product, e.g. IgG, were immobilized on a micro-porous gel and packed in small columns. After all IgG present in the sample was bound to the immobilized antibodies, unbound proteins were removed by rinsing the column. Elution of the bound antibodies followed and the antibodies were determined by fluorescence. The analytical procedure was automated with a robotic device to enable on-line measurements. The correlation between the on-line determined data and antibody concentrations measured by HPLC was linear.A sampling system was constructed, which was based on a pneumatically actuated in-line membrane valve integrated into the circulation loop of the reactor. Separation of the cells from the sample stream was achieved by a depth filter made of glass-fibre, situated outside the reactor. Rapid obstruction of the filter by cells or cell debris and contamination of the sample system was avoided by intermittent rinsing of the sample system with a chemical solution. The intermittent rinsing of the filter, which had a surface of 4.8 cm(2), resulted in an operational capacity of up to 40 samples (1.0 l total sample volume). Both the sampling system and the analytical device functioned without failure during this long-term culture.The culture temperature was varied between 34 and 40 °C. Raising the temperature from 34 up to 37 °C resulted in a simultaneous increase of growth and specific antibody production rate. Specific metabolic rates of glucose, lactate, glutamine and ammonium stayed constant in this temperature range. A further enhancement of temperature up to 40 °C had a negative effect on the growth rate, whereas the specific monoclonal antibody production rate showed a small increase. The other specific metabolic rates also increased in the temperature range between 38 to 40 °C.

A predictive model is developed for the filtration of noncoagulating particles in packed-bed depth filters. The model uses the trajectory analysis results of Rajagopalan and Tien (1976, A.I.Ch.E. J. 22 , 523–533) to calculate initial collection efficiencies of the granular media. Stochastic simulations of particle deposition are used to predict the decrease in collection efficiency that results from deposited particles not only occupying sites on the collector but also shadowing large deposition areas. A comparison of model predictions with data obtained form batch latex filtration experiments showed qualitative but not quantitative agreement. The observed decrease in collection efficiency could be described by a simple empirical expression, characterized by a single shadowing exponent, that was first suggested by Terranova and Burns (1991, Biotechnol. Bioengng 37 , 110–120). By developing a correlation for the shadowing exponent from the stochastic simulations and adjusting the expression for the initial collection efficiency, reasonably accurate model predictions could be made once the model parameters from a single experiment were determined. A study of the effect of dimensionless model parameters on predicted breakthrough curves showed that the optimal operating conditions to filter a given liquid suspension occur when the ratio of the particle-to-collector diameter is maximized. An approximate analytical solution is also developed to predict breakthrough behavior in lieu of a numerical solution.

The extraction of biopharmaceutical proteins from intact leaves involves the release of abundant particulate contaminants that must be removed economically from the process stream before chromatography, for example, using disposable filters that comply with good manufacturing practice. We therefore scaled down an existing 200-kg process for the purification of two target proteins from tobacco leaves (the monoclonal antibody 2G12 and the fluorescent protein DsRed, as monitored by surface plasmon resonance spectroscopy and fluorescence imaging, respectively) and screened different materials on the 2-kg scale to reduce the number of depth filtration steps from three to one. We assessed filter cost and capacity, filtrate turbidity, and protein recovery when the filter materials were challenged with extracts from different tobacco varieties and related species grown in soil or rockwool. PDF4 was consistently the most suitable depth filter because it was the least expensive, it did not interact significantly with the target proteins, and it had the greatest overall capacity. The filter capacity was generally reduced when plants were grown in rockwool, but this substrate has a low bioburden, thus improving process safety. Our data concerning the clarification of plant extracts will help in the design of more cost-effective downstream processes and accelerate their development.

The bioreactor volume delineating the selection of primary clarification technology is not always easily defined. Development of a commercial scale process for the manufacture of therapeutic proteins requires scale-up from a few liters to thousands of liters. While the separation techniques used for protein purification are largely conserved across scales, the separation techniques for primary cell culture clarification vary with scale. Process models were developed to compare monoclonal antibody production costs using two cell culture clarification technologies. One process model was created for cell culture clarification by disc stack centrifugation with depth filtration. A second process model was created for clarification by multi-stage depth filtration. Analyses were performed to examine the influence of bioreactor volume, product titer, depth filter capacity, and facility utilization on overall operating costs. At bioreactor volumes1,000 L, clarification using multi-stage depth filtration offers cost savings compared to clarification using centrifugation. For bioreactor volumes5,000 L, clarification using centrifugation followed by depth filtration offers significant cost savings. For bioreactor volumes of ∼ 2,000 L, clarification costs are similar between depth filtration and centrifugation. At this scale, factors including facility utilization, available capital, ease of process development, implementation timelines, and process performance characterization play an important role in clarification technology selection. In the case study presented, a multi-product facility selected multi-stage depth filtration for cell culture clarification at the 500 and 2,000 L scales of operation. Facility implementation timelines, process development activities, equipment commissioning and validation, scale-up effects, and process robustness are examined.

Ceramic filters, working on the depth filtration principle, are known to improve drinking water quality by removing human pathogenic microorganisms from contaminated water. However, these microfilters show no sufficient barrier for viruses having diameters down to 20 nm. Recently, it was shown that the addition of positively charged materials, for example, iron oxyhydroxide, can improve virus removal by adsorption mechanisms. In this work, we modified a common ceramic filter based on diatomaceous earth by introducing a novel virus adsorbent material, magnesium oxyhydroxide, into the filter matrix. Such filters showed an improved removal of about 4-log in regard to bacteriophages MS2 and PhiX174. This is explained with the electrostatic enhanced adsorption approach that is the favorable adsorption of negatively charged viruses onto positively charged patches in an otherwise negatively charged filter matrix. Furthermore, we provide theoretical evidence applying calculations according to Derjaguin-Landau-Verwey-Overbeek theory to strengthen our experimental results. However, modified filters showed a significant variance in virus removal efficiency over the course of long-term filtration experiments with virus removal increasing with filter operation time (or filter aging). This is explained by transformational changes of MgO in the filter upon contact with water. It also demonstrates that filter history is of great concern when filters working on the adsorption principles are evaluated in regard to their retention performance as their surface characteristics may alter with use.

Filtration is the separation of solid particles from a liquid or gas by forcing the mixture through a porous medium. It is widely applied in the food industry, and its importance is often linked to food safety. We distinguish between depth filtration and surface filtration. Depth filtration is applied to the purification of air and water. Surface filtration is applied more extensively. The product may be the separated solid (cake) or the fluid (filtrate). The rate of filtration is of considerable economic and technological importance. The basic mechanism of surface filtration is flow through porous media, quantified by Darcy’s Law and further developed as the Kozeny–Karman equation. The role of filter cake is analyzed and the use of filter aid is explained. Industrial filters include sand filters, depth filters for air, cartridge filters, filter presses, rotary vacuum filters and centrifuge filters. Expression, also known as pressing and squeezing, is an operation closely related to filtration, as it involves flow through a porous medium. Pressing for the expression of oils and juices is described. The influence of material properties and operation conditions on the rate and yield is discussed.

A depth filter perfusion system (DFPS), equipped with a 40-μm polypropylene depth filter for cell immobilization, was used for the continuous production of tissue plasminogen activator (t-PA) from recombinant Chinese hamster ovary cells. Final cell density in the DFPS with oxygen control was 1.8×107 cells/mL of the total working volume and maximum t-PA productivity was 2.63 mg/L/day. Dissolved oxygen concentration in the filter matrix was successfully controlled by air sparging and stable operation was possible for more than 20 days.

Fusion proteins offer the prospect of new therapeutic products with multiple functions. The primary recovery is investigated of a fusion protein consisting of modified E2 protein from hepatitis C virus fused to human IgG1 Fc and expressed in a Chinese hamster ovary (CHO) cell line. Fusion protein products inevitably pose increased challenge in preparation and purification. Of particular concerns are: (i) the impact of shear stress on product integrity and (ii) the presence of product-related contaminants which could prove challenging to remove during the high resolution purification steps. This paper addresses the use of microwell-based ultra scale-down (USD) methods to develop a bioprocess strategy focused on the integration of cell culture and cell removal operations and where the focus is on the use of operations which impart low shear stress levels even when applied at eventual manufacturing scale. An USD shear device was used to demonstrate that cells exposed to high process stresses such as those that occur in the feed zone of a continuous non-hermetic centrifuge resulted in the reduction of the fusion protein and also the release of glycosylated intracellular variants. In addition, extended cell culture resulted in release of such variants. USD mimics of low shear stress, hydrohermetic feed zone centrifugation and of depth filtration were used to demonstrate little to no release during recovery of these variants with both results verified at pilot scale. Furthermore, the USD studies were used to predict removal of contaminants such as lipids, nucleic acids, and cell debris with, for example, depth filtration delivering greater removal than for centrifugation but a small (~10%) decrease in yield of the fusion protein. These USD observations of product recovery and carryover of contaminants were also confirmed at pilot scale as was also the capacity or throughput achievable for continuous centrifugation or for depth filtration. The advantages are discussed of operating a lower yield cell culture and a low shear stress recovery process in return for a considerably less challenging purification demand.

Real-time depth of field (DoF) rendering is crucial to realistic image synthesis and VR applications. This paper presents a new method to simulate the depth-of-field effects with bilateral depth filtering. Unlike the traditional rendering methods that handle the depth-of-field with Gaussian filtering, we develop a new DoF filter, called adaptive bilateral depth filter, to adaptively postfilter the pixels according to their depth variance. Depth information is used to focus on the objects with edge-preserving property. Our approach can eliminate the artifacts of intensity leakage, which can generate adaptive high-quality DoF rendering effects dynamically, and can be fully implemented in GPU parallelization.

In drinking water treatment systems, the conventional process (coagulation, sedimentation and filtration units) cannot remove trace metals efficiently. Iron oxide is an excellent, regenerable adsorbent, and often controls free metals through adsorption. The utilization of heating process for coating iron oxide on sand surface allowed the media to be used in a packed column. The adsorbent media were investigated for removing copper ions from water using both batch and column experimental methods. A one-dimensional convective-dispersive transport model with a combination of second-order kinetic adsorption equation was adopted for predicting copper retention in a 80 cm depth filter bed. The concentration of copper ions in influent ranged from 0.64 to 3.2 mg/l. The experimental results indicated that the copper could be removed completely until the breakpoint. Once breakthrough occurred, the regeneration of the media could be achieved by soaking with acid solution (pH = 3.0). The simulation results of the transport-adsorption equation fit experimental data quite well. Consequently, the coated sand can be applied for the conventional rapid filtration process to remove copper ions from water.

Ceramic filter candles, based on the natural material diatomaceous earth, are widely used to purify water at the point-of-use. Although such depth filters are known to improve drinking water quality by removing human pathogenic protozoa and bacteria, their removal regarding viruses has rarely been investigated. These filters have relatively large pore diameters compared to the physical dimension of viruses. However, viruses may be retained by adsorption mechanisms due to intermolecular and surface forces. Here, we use three types of bacteriophages to investigate their removal during filtration and batch experiments conducted at different pH values and ionic strengths. Theoretical models based on DLVO-theory are applied in order to verify experimental results and assess surface forces involved in the adsorptive process. This was done by calculation of interaction energies between the filter surface and the viruses. For two small spherically shaped viruses (MS2 and PhiX174), these filters showed no significant removal. In the case of phage PhiX174, where attractive interactions were expected, due to electrostatic attraction of oppositely charged surfaces, only little adsorption was reported in the presence of divalent ions. Thus, we postulate the existence of an additional repulsive force between PhiX174 and the filter surface. It is hypothesized that such an additional energy barrier originates from either the phage's specific knobs that protrude from the viral capsid, enabling steric interactions, or hydration forces between the two hydrophilic interfaces of virus and filter. However, a larger-sized, tailed bacteriophage of the family Siphoviridae was removed by log 2 to 3, which is explained by postulating hydrophobic interactions.

In the underlying study we evaluated different single-use filtration systems for cell separation and harvest clarification in 1,000 L scale. A screening of different depth filters was carried out with various single-use filters from Pall, Cuno (3M), Millipore and Sartorius Stedim. In total, we included 85 depth filtrations in the screening. Out of that, two single-use filtration systems were chosen and further tested in 200 L scale. Based on these results, a single-use filtration set-up for harvesting production scale fed batch processes was determined.

Safe drinking water is still not accessible to more than 15% of the world’s population. Decentralised water treatment with ceramic filter candles at the point-of-use (POU) level provides a low-cost and single-stage filtration process with which pathogenic microorganisms can be removed. However, the retention performance of such depth filters scatters for microbiological contaminants in literature. The purpose of this study was to gain a better understanding on the removal mechanisms in ceramic depth filters based on the natural material diatomaceous earth (DE). Therefore, we manufactured so-called ceramic filter candles by ram-extrusion process and subjected these filters to a detailed physical characterisation regarding porosity, pore size distribution, specific surface area, flowrate, surface charge and microstructure. Next, we investigated experimentally the removal of colloidal latex (polystyrene) particles having diameters from 100 to 500 nm under various ionic strengths. Such particles were found to be removed due to adsorption of the colloids. Extended DLVO-theory was used to investigate the forces that account for the adsorption suggesting that hydrophobic interactions drag latex particles onto specific adsorption sites of the filter. It is hypothesised that these specific adsorption sites originate from the unique nanostructured surface of the diatomaceous earth. Furthermore, we believe that such latex particles may be suitable to model the removal of microorganisms if the surrogate and the target pathogen have similar characteristics.

Industrial fermentation takes into account many factors for economical production of desired products such as substrates and its conversion, product selectivity, product titer, productivity, and energy consumption. A new multistage continuous high cell density culture (MSC-HCDC) system assumes that cell density ( X ) is the most important factor in fermentation. The system under consideration consists of n -serially connected continuous stirred-tank reactors (CSTRs) with either hollow-fiber cell recycling or cell immobilization for high cell density having about 10-fold X . In each CSTR substrate, supply and product removal are possible. Examples of high cell density cultures in a single- and two-stage lactic acid and monoclonal antibodies are given as well as several multistage bioreactor operations for ethanol productions. MSC-HCDC system for monoclonal antibody (mAb) production was simulated based on two-stage HCDC experimental work with recombinant Chinese hamster ovary (rCHO) cells in the depth filter perfusion systems, which showed that MSC-HCDC can give the product ratio (PR) of about 10 achieving equivalent product titer of fed-batch system. The PR is defined as D t · θ B/FB , where D t and θ B/FB are system dilution rate of MSC-HCDC and cycle time of batch or fed-batch (B/FB) system, respectively. MSC-HCDC can be considered as a new production platform for various fermentation products including mAb.

Depth filtration of liquids is a well established process. Its main drawback is that it does not effectively remove particles smaller than about 2-3 µm diameter, because they do not normally approach near enough to the surface of the medium to become attached to it. A static electrical field overcomes this by promoting electrophoretic movement of the particles. The work has studied particle removal from low conductivity water through fibrous depth filters and has covered a variety of fibres with different physical properties. The results yield a fibre efficiency series, which suggest the relationship between filtration efficiency and the electrical properties of the fibre.

The new Poly-Fine ARD incorporates into a single device design an absolute rated fixed pore structure final filter with a graded pore size outer prefilter depth matrix. This combination of surface and depth filter mechanisms results in an extremely versatile filter that can provide high performance filtration of particles down to 1 μm and below under a variety of operational conditions. The filter design allows many current nominal depth filter applications to be upgraded for improved filtrate quality at an economical cost. The ARD can also provide value improvement to many absolute surface filter applications, maintaining or improving filtrate quality while actually reducing filtration costs. The novel approach to the ARD manufacturing technology provides superior control over product consistency, repeatability and cleanliness. Comparative tests with other filters serving the same applications have demonstrated the ARD's improved service life, flow rates and removal efficiency. It has been highly successful in many applications including fine chemicals, pre-RO and ultrapure water, coatings, and beverages. The Poly-Fine ARD represents a new and valuable tool for filtration unit process improvements. Its unique performance features meet the challenge of increasing quality filtration demanded by the competitive global market place.

The specific objective of this research was to revise an existing depth filter ripening model designed for monodisperse suspensions to account for heterodisperse suspensions and to calibrate and test the resulting model with experimental results. The comparison of the detailed experimental results with the mathematical model provided a good test of the model to handle both conditions for which it was designed and conditions for which it was not designed. When calibrated with results of the monodisperse experiments, the model did a poor job of predicting filtration performance in the bi-modal and tri-modal experiments; however when calibrated with results of non-monodisperse experiments, the model performed significantly better.

The aerosol of surgical plume could be measured effectively with the use of bacteriophage ΦX-174 as a biological marker, in contrast to previous methodologies reported by others. Recovery of virus plaqueforming units was highest from hydrophobic polytetrafluoro-ethylene membranes compared to hydrophobic polycarbonate screen filters or polyvinylidene difluoride depth filters, indicating that the method of virus recovery strongly affects the utility of a virus as an aerobiological marker. With this new method, surgical plume was indeed found in significant amounts when cutting tissue phantoms made with agar containing virus. The Electromagnetic Field Focusing System was used, which is a new thermal surgical device. The nominal power setting did not appear to be a factor in the amount of virus recovered. However, when pulse modulating the power by adjusting the crest factor from 1·4 to 4·3, a measure of the duty cycle for power delivery which adjusted the device from its cutting to haemostatic mode, a nearly five-fold increase in surgical plume, as evidenced by the recovery of ΦX-174 plaque forming units, was seen. The data indicate that bacteriophage ΦX-174 can be used effectively as an aerobiological marker for aerosols generated during clinical procedures, and reinforce the need to use a safety vacuum during aerosol generating procedures. The availability of a safe and economical biological marker for aerosols from clinical procedures, which may lead to acquired infections in hospital personnel, makes evaluation of procedures and containment systems markedly easier. The data also indicates that surgical plume biohazard may be present in other techniques that employ pulse modulation including surgical lasers and electrocauteries.

Cuno developed the charge modified cellulose depth filter in response to increasing concerns over the use of asbestos based filter media in the pharmaceutical industry. The subsequent ban on asbestos in filter media was extended to other industries due to greater understanding of the dangers posed by asbestos. The charge modification technique has been applied to other types of substrates to produce novel filter media as Sailesh Patel, Cuno UK, explains.

We herein describe a new depth filter media which exhibits selective adsorption properties for lipids of plasma on Zeta Plus Del I (Cuno Europe). Lipids plug chromatographic columns and filter during plasma fractionnation and cause solution instability for the final product. Several parameters which could affect the lipid removal efficiency on Zeta Plus Del I have been investigated: prefiltration, contact time, ionic strength, pH, and temperature. The maximum percentage of total lipids eliminated, in the better operating conditions was 68%. This method has proven to be efficient for the treatment of plasmatic lipids and can be easily incorporated in an industrial process.

The removal of the abnormal form of prion protein i.e. PrP(SC) by filtration steps in the plasma fractionation process has been investigated by immuno-Western blotting. Depth filtration has been shown to be capable of removing scrapie by 2-3 log from certain plasma product intermediates. These include cryoprecipitate supernatant, used for the manufacture of immunoglobulin and albumin, and albumin fraction V, by filtration using Pall Seitz or 3m Cuno depth filters respectively. However no significant removal occurred with immunoglobulin Fraction II after Cuno depth filtration. When 0.2 microm PVDF and Nylon membrane filters were tested, the removal of TSEs from 20% albumin was limited i.e. 0.6-1.3 log. However under protein free conditions using phosphate buffered saline, filtration was not effective in the case of a PVDF filter but very effective i.e. >2.9 log in the case of a Nylon filter.

The aim of this work was to recover albumin from Kistler and Nitschmann's fraction IV using membrane chromatography. The best solubilization results were obtained at pH 6.5 using a phosphate buffer containing 150 mM NaCl. More than 90% of the initial albumin content was recovered. The purification procedure included 2 main steps: the first one was a depth filtration in order to remove fine particles and a selective depth filter treatment for lipid removal. The second step was ion exchange chromatography. We used membrane chromatography systems where the fluid flows radially allowing fast flow purification under low operating pressures. The eluted albumin was free from IgG. Because of the absence of contaminating IgG and its high microbiological quality compared to standard animal sera, this albumin preparation can be used as a culture medium additive. It can also be further purified by ultrafiltration. The equipment used here is easy to handle and to sterilize, and meets the FDA Code of Federal Regulations. Additionally, this procedure is flexible enough to allow the co-purification of other fraction IV proteins such as transferrin or alpha-1-anti-trypsin.

The febrile reaction that occurs on reinfusion of ascites was studied. Intravenous reinfusion of ascites was performed 213 times in 63 cases of ascites, which were refractory to treatment with various drugs including diuretics. In order to prevent fever on reinfusion of ascites, a screen filter and a depth filter were used; the results were more favorable with the screen filter. Fibrin was considered to be one of the substances removable by the screen filter. HPLC analysis of the filtered and concentrated ascites, after passage through the screen filter, revealed a fraction corresponding to albumin. Intravenous injection of this fraction into rabbits caused fever. Although the screen filter cannot completely prevent fever on reinfusion of ascites, it appears useful to prevent fever in some patients.

This chapter explores many different types of filters that are available for processes such as strainers, presses, and filters aided by magnet, electricity, or centrifugal force. The filters are divided by the force that causes filtration: vacuum (i.e., a negative pressure at the filter medium), gravity alone (i.e., the hydrostatic head of the liquid above the medium), centrifugal force (i.e., an amplified gravity effect), fluid pressure (imposed by the suspension feed pump), mechanical pressure (a squeezing effect), and the use of other force fields. The large number of types of pressure filters is obvious—for most people the pressure filter, from simple cartridge to the complex fully automated filter press, typifies filtration. The range of gas filtration equipment is much smaller than that for liquids. This is because the recovery of solids from a gas suspension is a task not often undertaken in a filter, a cyclone being used instead. Gas filtration is almost always a decontamination process, whether it is of inlet air to buildings or machinery, or of exhaust streams from machines or processes. Solids recovery from liquid suspension, on the other hand, is a task frequently undertaken by filters, and the wide variety of types of liquid filters is almost entirely because of the problems imposed on filter design by the need to remove these collected solids from the inside of the filter.

In this paper, we proposed an early depth test method which extends a pixel-level depth filter to a triangle-level depth filter. This method decides whether the triangles are removed as well as pixels by a mask plane called depth filter (DF). The proposed method evaluates the DF in the triangle-level by using a hierarchical map of the conventional DF; thus the method removes the invisible triangles before the rasterization. Therefore, the rasterization performance can be increased and the bandwidth is further saved than the conventional DF. As the simulation results using complex scenes, the memory bandwidth is reduced by up to 31% compared with the conventional pixel-level DF method

An efficient depth image based rendering with edge dependent depth filter and interpolation is proposed. The proposed method can solve the hole-filling problem in DIBR system efficiently with high quality. The PSNR of the proposed method is better than the previous work by 6 dB and the subjective view shows the quality is better. In addition to that, the number of instruction cycles is 3.7 percent compared with the previous work

Depth filtration can be very attractive for initial clarification because of low capital costs and ease of operation. However, there is currently no fundamental understanding of the effects of the filter pore size and morphology on the overall capacity and filtrate quality. The objective of this study was to examine the flux, capacity, and filtrate turbidity of a series of depth filters with different pore size ratings and multilayer structures for the filtration of yeast cell suspensions. Data were analyzed using available fouling models to obtain insights into the flux decline mechanisms. Filters with small pore size provide high filtrate quality at low capacity, with the reverse being true for the larger pore sizes. The multilayer structure of commercial depth filters leads to improved performance, although the choice of layer properties is critical. The highest capacity was achieved using a multilayer filter in which the upper layer allows significant yeast cell penetration into the filter matrix but still protects the retentive layer that is needed for a high quality filtrate.

Low abrasive content and much smaller mean particles of silica, alumina and ceria abrasives in new generation chemical mechanical planarization (CMP) slurries demand much tighter retention of /spl ges/0.5 /spl mu/m and even smaller particles with least effect on the mean working particles. Current slurry manufacturing processes target 90% and higher reduction of cumulative large particle counts (LPCs) at /spl ges/0.56 or 1.01 /spl mu/m in a single pass. Filtration using graded density, multiple thin-layer, and pleated depth filter media or membranes can provide needed retention depending on the slurry characteristics. Efficient slurry filter design must consider slurry abrasive type and morphology, LPCs, mean particle size distribution (PSD), wt% solids, oxidizers, chemicals and organic additives, blending protocols, viscosity, abrasive settling rate, target retention level, pressure drop (/spl Delta/p) limits, flow rate stability and expected filter lifetime. Results of retention, flow rate and /spl Delta/p from filtration tests using 0.50 and 1.0 /spl mu/m nominal rating depth media samples show very different behavior in silica, alumina and ceria slurries, confirming that newer CMP slurries filter optimization still remains empirical in nature. This study shows that laboratory and field characterizations, and post-use filter analysis are useful in filter optimization. This study demonstrates that the filtration of newer CMP slurries is useful in managing large particles.

We evaluated the efficiency of five membrane filters for recovery of Cryptosporidium parvum oocysts and Giardia lamblia cysts. These filters included the Pall Life Sciences Envirochek (EC) standard filtration and Envirochek high-volume (EC-HV) membrane filters, the Millipore flatbed membrane filter, the Sartorius flatbed membrane filter (SMF), and the Filta-Max (FM) depth filter. Distilled and surface water samples were spiked with 10 oocysts and 10 cysts/liter. We also evaluated the recovery efficiency of the EC and EC-HV filters after a 5-s backwash postfiltration. The backwashing was not applied to the other filtration methods because of the design of the filters. Oocysts and cysts were visualized by using a fluorescent monoclonal antibody staining technique. For distilled water, the highest percent recovery for both the oocysts and cysts was obtained with the FM depth filter. However, when a 5-s backwash was applied, the EC-HV membrane filter (EC-HV-R) was superior to other filters for recovery of both oocysts ( n = 53 ± 15.4 per 10 liters) and cysts ( n = 59 ± 11.5 per 10 liters). This was followed by results of the FM depth filter (oocysts, 28.2 ± 8, P = 0.015; cysts, 49.8 ± 12.2, P = 0.4260), and SMF (oocysts, 16.2 ± 2.8, P = 0.0079; cysts, 35.2 ± 3, P = 0.0079). Similar results were obtained with surface water samples. Giardia cysts were recovered at higher rates than were Cryptosporidium oocysts with all five filters, regardless of backwashing. Although the time differences for completion of filtration process were not significantly different among the procedures, the EC-HV filtration with 5-s backwash was less labor demanding.

This paper describes the structure and testing of two novel permanently magnetized magnetic filters for fine radioactive material. In the first filter the holes in the filter are left open as capture proceeds which means the pressure drop builds up only slowly. This filter is not suitable for composite particles which can be broken by mechanical forces. The second filter has been changed so as to strongly capture particles composed of fine particles weakly bound together which tend to break when captured. This uses a principle of assisted capture in which coarse particles aid the capture of the fine fragments. These filters have the following characteristics: (1) no external magnet is required; (2) no external power is required; (3) small in size and portable; (4) easily interchangeable; (5) can be cleaned without demagnetizing by using a magnetic fluid which matches the susceptibility of the captured particles.

Magnetically Assisted Gasification (MAG) is a relatively new concept for the destruction of solid wastes aboard spacecraft, lunar and planetary habitations. Three sequential steps are used to convert the organic constituents of waste materials into useful gases: filtration, gasification, and ash removal. In the filtration step, an aqueous suspension of comminuted waste is separated and concentrated using a magnetically consolidated depth filter composed of granular ferromagnetic media. Once the filter is fully loaded, the entrapped solids are thermochemically gasified via a variety of mechanisms including pyrolysis, isomerization, and oxidation reactions. Finally, the inorganic ash residue is removed from the magnetic media by fluidization and trapped downstream by filtration. Importantly, for each of these steps, the degree of consolidation or fluidization of the granular ferromagnetic media is controlled using magnetic forces. This makes possible the application of the MAG technology in a variety of gravitational environments, including microgravity, hypogravity, and 1 g. In this paper we summarize the development of Gradient Magnetically Assisted Filtration and Fluidization methods which are essential components of the MAG process. Numerical models representing filtration and fluidization phenomena are described. The results of both laboratory and µg flight experiments are presented and compared to the outcomes predicted by the mathematical models.

Background and Objectives Plasma-derived therapeutic proteins have the potential to contain transmissible spongiform encephalopathy (TSE) infectivity. This study evaluated the effectiveness and characterized the mechanism of abnormal prion protein removal during a depth-filtration step used in the manufacture of an immunoglobulin preparation. Materials and Methods Scrapie brain homogenate was treated with lysolecithin, sonicated and sequentially filtered through 0.45-, 0.22- and 0.1-μm membrane filters. The scrapie brain homogenate was then added (at a 1: 51 dilution) to the Supernatant III fraction used in the manufacture of Rh 0 (D) immune globulin (human). The spiked immunoglobulin preparation was then filtered through a depth filter under the same conditions used in full-scale production. After filtration, the depth filter was washed with hypertonic NaCl solutions to elute the abnormal prion protein (PrP Sc ) from the filter. A Western blot assay for PrP Sc was used to quantify removal from the filtrate and recovery from the filter washes. A second run was performed whereby the PrP Sc -spiked Supernatant III was filtered through a 0.22-μm membrane filter prior to depth filtration. A third run evaluated depth filtration of PrP Sc in Tris-buffered saline (TBS). Results The depth filter removed greater than four logs of PrP Sc from the Supernatant III filtrate. A significant portion of the PrP Sc could be recovered from the depth filter by elution with high-molarity NaCI solutions. Prefiltration (through a 0.22-μm membrane filter) of the spiked Supernatant III prior to depth filtration removed all detectable PrP Sc . Depth filtration removed less than one log of PrP Sc from TBS. Conclusions Depth filtration appears to remove PrP Sc from the immunoglobulin preparation by mechanical straining rather than by adsorption to the filter matrix. The immunoglobulin preparation caused the PrP Sc to aggregate from particles 0.22 μm, probably as a result of the presence of methanol in the preparation. The depth filter failed to remove PrP Sc from a purely aqueous environment.

Introduction Sterilization by Heat Autoclaves Hot Air Ovens and Incineration Filtration Depth Filters Membrane Filters Using Filters Integrity Testing Fumigation Formaldehyde Ethylene Oxide Gamma Irradiation Ultraviolet Light Liquid Disinfectants Formaldehyde and Glutaraldehyde Hypochlorite Phenolics Alcohol Other Disinfectants Virus Testing and Elimination Prions Regulatory and Safety Issues Safety Requirements Good Manufacturing Practice Good Laboratory Practice Bibliography Keywords: good laboratory and manufacturing practice; antibiotics; filtration; fungicides; biocides; irradiation