6 research outputs found

    Interaction between membrane and protein properties on flux decline during sterile microfiltration

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    Department Head: Stuart A. Tobet.Includes bibliographical references (pages 63-66).Microfiltration is widely used in industry to filter out particulate matter that contaminates or slows down the performance of the membrane. In the biopharmaceutical industry in particular, bacteria, microorganisms and viruses are filtered out using sterile microfiltration. Numerous studies have been conducted to further the understanding of flux decline due to protein fouling. Many times the operating conditions, the type of membrane and type of protein all interact to have an effect on protein fouling and flux decline. Normal-flow microfiltration experiments were conducted using uncoated polytetrafluoroethylene (PTFE) and polyvinylidene fluoride (PVDF) membranes, and PTFE and PVDF membranes coated with polyvinyl alcohol (PVA). Feed streams consisted of lysozyme, β-lactoglobulin and ovalbumin. The pH values of the solution were set at the isoelectric point of each of the proteins (11.0, 5.8, and 4.7 respectively). The experiments were operated with a feed pressure of 2 or 10 psi. Each of the proteins was tested at 0.1 and 2 g/L with uncoated PTFE. No flux decline was seen using 0.1 g/L, so 2 g/L was focused on for PVA coated PTFE, PVA coated PVDF and uncoated PVDF membranes. Protein fouling of the membrane was investigated by determining the variation of permeate flux versus filtrate volume and by analysis of Attenuated Total Reflection-Fourier Transform Infrared (ATR-FTIR) spectra and Field Emission Scanning Electron Microscopy (FESEM) images of unfouled membranes and membranes after microfiltration. Results indicate that the greatest amount of fouling occurs with ovalbumin. The order of most to least fouling was found to be ovalbumin> β-lactoglobulin>lysozyme. Fouling was more severe at the higher protein concentration (2 g/L) and feed pressure (10 psi) and seen only when filtering the solution through uncoated and PVA coated PTFE. Flux decline under these conditions was analyzed using classical pore blockage models. In general, flux decline was found to be caused by complete pore blocking. In the case of ovalbumin filtered through PVA coated PTFE, the flux decline was first caused by pore blockage and then later transitioned to cake filtration. The proteins which showed significant fouling conditions were looked at more closely by pre-filtering the protein solution. The goal of pre-filtration was to decrease any protein aggregates present in solution. This pre-filtration step was conducted with 0.2, 0.45 and 1 μm diameter pore sizes. The flux decline when pre-filtering the feed solution with 1 μm pores was equivalent to the filtration experiments without pre-filtration. The only significant decrease in flux was present when pre-filtering with the 1μm pores. Additional experiments were conducted using hemoglobin (Hb) at 2 g/L and 10 psi operating conditions. Previous literature had shown that using 1 μm pre-filtration, there was severe flux decline for uncoated and PVA coated PTFE. To follow up on these experiments, Hb was pre-filtered using 0.2 and 0.45 μm pre-filtration membranes and then filtered through uncoated and PVA coated PTFE. These experiments resulted in no flux decline. The Hb experiments verified the results from the ovalbumin and β-lactoglobulin experiments. All together, these results indicate that there is an interaction among membrane properties, protein properties, operating conditions and pre-filtration characteristics that determine whether fouling occurs and to what extent

    Evaluating filtration membranes and detection systems for use with virus surrogates

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    Department Head: Susan P. James.2010 Summer.Includes bibliographical references (pages 41-45).Virus filtration membranes are used to provide size exclusion removal of viruses during the purification of biopharmaceutical products. This viral clearance is required by regulatory agencies to ensure the safety of patients by preventing contamination of product by adventitious or endogenous virus. Viral clearance studies are often laborious, expensive, and require highly trained personnel. Detection and quantification of virus using standard assays has restrictions in terms of limit of detection, extraneous contamination and false positives. Moreover, biosafety for personnel and the environment is always a concern when working with live virus. In order to avoid the hazards of live, adventitious virus, bacteriophages have been used previously as virus surrogates (Aranha-Creado & Brandwein, 1999). While the health threat associated with using live viruses is eliminated using bacteriophages as surrogates, the detection systems and quantitative assays are still laborious and difficult. Development of a non-biological system to simulate and quantify virus particles could reduce the time taken to perform viral clearance tests; reduce development costs; reduce the risk to personnel performing the tests; and lead to more reliable data, since a non-biological system will reduce variability in assays. Here we develop a prototype of a novel, gigantic magnetoresistive (GMR) detection system for magnetic virus surrogates. In addition, we investigate various polymeric membranes for their ability to reject virus. Results will be used as a benchmark for evaluating the behavior of a future, superparamagnetic virus surrogate. GMR-based technology has increasingly been on the rise since the 2007 Nobel Prize in physics was awarded to Albert Fert and Peter Grünberg for its discovery. GMR sensors show potential for being extremely sensitive, inexpensive, and flexible devices for use in biodetection assays. Compared to the current magnetic detection technology of the superconducting quantum interference device (SQUID), which requires complex instrumentation and qualified users, GMR technologies can be fabricated in such a manner so as to be applied to lab-on-chip systems. Here we discuss the sensor design and fabrication. Initial measurements indicate that 104 iron oxide nanoparticles, approximately 20nm in diameter, can be detected in 0.5μl of solution. Various virus filters as well as ultrafiltration membranes were challenged with feed streams spiked with high concentrations of minute virus of mice (MVM) in the presence and absence of 1% bovine serum albumin (BSA) (w/v). Changes in permeate flux with filtrate volume were determined in conjunction with changes in rejection of parvovirus. Decrease in permeate flux resulting from fouling of BSA was evaluated for its effect on virus rejection. The results, which compare the performance of virus filtration and similar ultrafiltration membranes, provide insights into the comparison of live virus with future virus surrogates

    Inverse colloidal crystal membranes: formation, surface modification and applications

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    2010 Fall.Includes bibliographical references.Inverse colloidal crystal (ICC) membranes have many advantages, such as highly uniform pore size, fully interconnected pores, and high porosity, over commercially available porous membranes as a selective barrier for ultrafiltration and microfiltration. However, making an ICC membrane which is applicable in separations using reported ICC membrane formation methods has been still not successful yet. We describe here a new ICC membrane formation method, vertical cell (VC) assembly method, to make ICC separation membranes in a simple, low-cost way. The VC assembly method is a versatile colloidal crystal assembly method which is specifically designed for making ICC membranes. Formation of colloidal crystal films(CCF), which is the first step in formation of the inverse colloidal crystal membrane, to large extent determines how good the final membrane properties. The vertical cell assembly method is described that yields CCFs with surface areas up to 5 cm2 and thicknesses up to 100 μm. The thickness of the CCF can also be easily controlled by the spacer which is used. Based on the new ICC membrane formation method, the ICC membranes have been fabricated with a variation of pore-sizes and thicknesses. The membrane casting cell facilitates easy variation of membrane thickness. The membrane pore size is varied by changing the diameter of the silica spheres used to prepare the colloidal crystal template. By changing the composition of the reactive monomer solution, the ICC membranes have been fabricated with different hydrophobicities. Following synthesis, the ICC membranes were tested in a commercially available stirred cell. Particle fractionation was studied in normal flow filtration experiments. The membrane produced from 835 nm particles and 100 μm spacer gives a good passage for 60 nm particles in 60-835 nm bidisperse particle suspension while gives poor passage for the same size paritcles in 60-440 nm bidisperse particle suspension. Fabrication of a UF membrane requires a much smaller pore size. However, for making the ICC membranes with pore size in UF range, it is hard to make them just relying on using small SiO2 particles. This would lead to poor membrane mechanical strength. Here, I described a way to reduce the ICC membrane pore size by growing a uniform poly (poly ethylene glycol methacrylate) (PPEGMA) nano-layer from the membrane surface using surface initiated atom transfer radical polymerization. There are two purposes for the surface modification. One is to control membrane pore size. The other is to improve the membrane surface hydrophobicity. The grafted membranes were characterized with SEM, XPS, ATR-FTIR and water contact angle measurement. Dextran rejection test was conducted on the modified membrane with modification time of 3hr. The rejection rate was obtained for dextran with Mw from 1 kDa through 2000 kDa. The tested membrane shows more than 80% rejection for Dextran with MW more than 100 kDa, and a partial rejection for Dextran with Mw from 10 kDa to 100 kDa, and a less than 20% rejection for Dextran with MW smaller than 10kDa

    Reactive membrane extraction in biorefineries

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    2011 Spring.Includes bibliographical references.Separations account for 60-80% of the processing costs of most mature chemical processes. Membrane based separations offer several advantages over conventional technology such as lower energy costs and easy scale up. Here we focus on membrane extraction for removal of acetic acid, sulfuric acid, furfural, HMF and other toxic compounds from biomass hydrolysates. As membrane extraction is non-dispersive it overcomes the disadvantages of conventional extraction. Experiments have been conducted using dilute sulfuric acid pretreated corn stover (hydrolysate). Acetic acid, in its protonated form, is extracted into an organic phase consisting of octanol/oleyl alcohol and Alamine 336, a tertiary amine, containing aliphatic chains of 8-10 carbon atoms. Co-extraction of sulfuric acid leads to an increase in hydrolyste pH. The effect of aqueous and organic phase flow rates and temperature, on the rate of extraction of acetic acid and sulfuric acid has been investigated. Changes in the rates of acetic and sulfuric acid extraction may be explained by considering the structure of the complexes formed in the organic phase. We conducted computational modeling to elucidate the extraction process of Alamine 336 in different solvents. Extraction of carboxylic acids, Furfural and HMF in water and octanol was simulated using the Gaussian 03 package. In the past the extraction process has been explained by the direct interaction of the carboxylic acid with the Alamine 336 to form an ion pair. More carboxylic acids could be extracted through hydrogen bonding forming a dimer or trimer complex form with the Alamine 336, stabilized by the organic solvent. Hydrolysates treated by membrane extraction and conventional conditioning technologies were fermented using a glucose-xylose fermenting bacteria to determine the viability of membrane technology to detoxify biomass hydrolysates. Membrane extraction could be a viable hydrolysate detoxification technology because the other conditioning technologies do not remove acetic acid

    Can researchers trust ICD-10 coding of medical comorbidities in orthopaedic trauma patients?

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    Abstract. Objectives:. The 10th revision of the International Classification of Diseases (ICD-10) coding system may prove useful to orthopaedic trauma researchers to identify and document populations based on comorbidities. However, its use for research first necessitates determination of its reliability. The purpose of this study was to assess the reliability of electronic medical record (EMR) ICD-10 coding of nonorthopaedic diagnoses in orthopaedic trauma patients relative to the gold standard of prospective data collection. Design:. Nonexperimental cross-sectional study. Setting:. Level 1 Trauma Center. Patients/Participants:. Two hundred sixty-three orthopaedic trauma patients from 2 prior prospective studies from September 2018 to April 2022. Intervention:. Prospectively collected data were compared with EMR ICD-10 code abstraction for components of the Charlson Comorbidity Index (CCI), obesity, alcohol abuse, and tobacco use (retrospective data). Main Outcome Measurements:. Percent agreement and Cohen's kappa reliability. Results:. Percent agreement ranged from 86.7% to 96.9% for all CCI diagnoses and was as low as 72.6% for the diagnosis “overweight.” Only 2 diagnoses, diabetes without end-organ damage (kappa = 0.794) and AIDS (kappa = 0.798) demonstrated Cohen's kappa values to indicate substantial agreement. Conclusion:. EMR diagnostic coding for medical comorbidities in orthopaedic trauma patients demonstrated variable reliability. Researchers may be able to rely on EMR coding to identify patients with diabetes without complications or AIDS. Chart review may still be necessary to confirm diagnoses. Low prevalence of most comorbidities led to high percentage agreement with low reliability. Level of Evidence:. Level 1 diagnostic
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