Sadettin Ozturk

Sadettin Ozturk
STRM.BIO

Doctor of Philosophy

About

58
Publications
6,921
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2,254
Citations
Citations since 2016
3 Research Items
523 Citations
2016201720182019202020212022020406080
2016201720182019202020212022020406080
2016201720182019202020212022020406080
2016201720182019202020212022020406080

Publications

Publications (58)
Article
Background: Graves’ disease has a multitude of effects on the cardiovascular system. In the detection of subclinical left ventricular dysfunction, speckle-tracking echocardiography is more useful than conventional echocardiography. The aim of the present study was to compare the longitudinal global strain values and venous blood concentration of (t...
Chapter
This chapter presents cell culture technologies enabling the production of biopharmaceuticals using continuous biomanufacturing. Different types of continuous cell culture systems are discussed with a special attention to perfusion cultures. The drivers for a continuous bioproduction are outlined, and the challenges in their implementation are disc...
Chapter
This chapter presents the opportunities and discusses the challenges for the implementation of continuous processing in biomanufacturing. Although batch processes are more common in the biopharmaceutical industry, continuous processing have been employed for some of the biomanufacturing steps, mainly for culturing the cells in bioreactors and gener...
Article
Full-text available
Abstract A common challenge encountered during development of high concentration monoclonal antibody formulations is preventing self-association. Depending on the antibody and its formulation, self-association can be seen as aggregation, precipitation, opalescence or phase separation. Here we report on an unusual manifestation of self-association,...
Article
Full-text available
A common challenge encountered during development of high concentration monoclonal antibody formulations is preventing self-association. Depending on the antibody and its formulation, self-association can be seen as aggregation, precipitation, opalescence or phase separation. Here we report on an unusual manifestation of self-association, formation...
Article
This chapter provides information on commonly used equipment in industrial mammalian cell culture, with an emphasis on bioreactors. The actual equipment used in the cell culture process can vary from one company to another, but the main steps remain the same. The process involves expansion of cells in seed train and inoculation train processes foll...
Article
Full-text available
Size exclusion high performance liquid chromatography analysis of a human monoclonal antibody (mAb) showed the presence of a new species that eluted with a retention time between the dimeric and monomeric species of the antibody. Extensive characterization of this species, referred to as "shoulder," indicated that it was a mAb containing an extra l...
Chapter
The Process Analytical Technology (PAT) guidance and Quality by Design (QbD) concepts from the US Food and Drug Administration (FDA) was published in 2004 (FDA Guidance for Industry). It has been introduced by many companies to better understand and design new processes effectively by attributing key product quality parameters within a well-defined...
Chapter
Bioprocess development requires the use of scale-down models for clone selection, media optimization, process development and characterization. Different models are commonly used at various stages: well plates and shake flasks for clone selection, shake flasks and bench-top bioreactors for media optimization and process development, bench-scale and...
Article
In power systems transients caused by energization of power transformers and voltage dip are some of the more common problems. Voltage recovery after a voltage dip can produce transformer saturation. This saturation produces an inrush current similar to that of the transformer energizing. In this paper transformer inrush current resulting by voltag...
Conference Paper
Eigenvalues of a power system can explain the system stability in its operating point. In this paper the linear analysis capabilities of two software packages are evaluated and compared. The paper also illustrates the impact of the models of the power system components (like generators) on the location of the eigenvalues. Eigenvalue analysis are no...
Conference Paper
This paper presents the usage and some studies of an under/over voltage relay which is a part of electric power system designed for constant voltage operation. Electrical characteristics are derived from data sets which belongs to the studied system and the system is modeled by using the artificial neural networks.
Article
Oxygen consumption rates were measured in a respirometer for different mammalian cell lines (BHK, murine hybridoma, and CHO), and the effects of cell density (1-20 million cells/mL) and temperature (6 to 37 degrees C) on specific oxygen consumption rate were investigated. The specific oxygen consumption was cell line dependent. For a given temperat...
Article
On-line monitoring and control of cell culture fermentation is important for optimal and consistent production of biologicals. In this work, glucose and lactate concentrations are monitored on-line using a commercially available analyzer (Model 2700, Yellow Springs Instruments, Yellow Springs, OH) during batch and perfusion hybridoma cell fermentat...
Chapter
Glucose is a major energy source for mammalian cells grown in culture. Although conditions are aerobic, in most cases, glucose is not completely oxidized. Depending on the culture conditions and the cell type, about 50-100% of glucose is converted to lactate. In this study, the glucose metabolism was studied in batch, chemostat, and perfusion cultu...
Chapter
Despite all efforts, process monitoring and control of mammalian cell cultures are still limited to physical variables such as pH, DO, and temperature. Although these are important parameters, cellular activities are equally governed by the biochemical composition of the media in the fermenter. If the cellular environment is not controlled, then ce...
Article
High density cell culture systems offer the advantage of production of bio-pharmaceuticals in compact bioreactors with high volumetric production rates; however, these systems are difficult to design and operate. First of all, the cells have to be retained in the bioreactor by physical means during perfusion. The design of the cell retention is the...
Article
On-line, "real-time" monitoring of product concentration is important for mammalian cell culture fermentation. The continuous measurement of monoclonal antibodies allows for instantaneous determination of cell productivity and effective manipulation of the fermentor operating conditions for optimal production. This article will present the evaluati...
Article
On-line optical cell density probes were implemented to continuously monitor the cell densities in mammalian cell bioreactor and to achieve advanced bioreactor controls. We tested cell density probes from six manufacturers in high cell density bioreactors. When externally calibrated, Aquasant and Ingold backscattering probes produced the most linea...
Chapter
A perfusion bioreactor system has been developed for independent control of cell density and metabolite concentrations. The cell density was monitored and controlled using an online optical sensor. A constant environment to the cell was provided by controlling metabolite concentrations. This was accomplished by altering the perfusion rate using a k...
Chapter
High density cell culture systems offer more than a one-order of magnitude increase in reactor productivity. The design and scale-up of these systems are, however, more difficult. The challenges start with the mechanical design of the bioreactors; mixing and mass transfer are more critical in high density systems. In this paper, we analyze several...
Chapter
Culture productivity and product titer can significantly affect the economics of large-scale production of biotherapeutics. Bioreactor space-time productivity is determined by cell density and cell-specific productivity, while product titer is determined by medium feed rate per cell and cell-specific productivity. Therefore, high space-time product...
Article
Full-text available
The influence of ammonia and lactate on cell growth, metabolic, and antibody production rates was investigated for murine hybridoma cell line 163.4G5.3 during batch culture. The specific growth rate was reduced by one-half in the presence of an initial ammonia concentration of 4 mM. Increasing ammonia levels accelerated glucose and glutamine consum...
Chapter
Verax Corporation has pioneered the use of natural collagen macroporous microcarriers (Microspheres) for the small and large-scale cultivation of animal cells, both attachment preferred and suspension cells. Collagen Microspheres containing cells are cultured in fluidized-bed bioreactors to very high densities (> 108 viable cells per mL of matrix)...
Article
A mouse-mouse hybridoma cell line (167.4G5.3) was cultivated in a 1.5-L stirred-tank bioreactor under constant pH and dissolved oxygen concentration. The transient kinetics of cell growth, metabolism, and antibody production were followed by biochemical and flow cytometric methods. The cell-specific kinetic parameters (growth and metabolic rates) a...
Article
The effects of serum, dissolved oxygen (DO) concentration, and medium pH on hybridoma cell physiology were examined in a controlled batch bioreactor using a murine hybridoma cell line (167.4G5.3). The effect of serum was also studied for a second murine hybridoma cell line (S3H5/gamma 2bA). Cell growth, viability, cell density, carbohydrate and ami...
Article
Full-text available
A murine hybridoma cell line (167.4G5.3) was cultured in batch mode using IMDM containing different serum concentrations and bovine serum albumin (BSA). Cell growth and death, metabolism and antibody production were studied in these cultures. The cells were more susceptible to shear in the stationary and in the decline phase of growth as evidenced...
Article
Full-text available
Osmolarity is an important process variable during the cultivation of mammalian cells in vitro. Cell culture medium is designed to have osmolarity in the range of 260 and 320 milliosmoles (mOsm), basically to mimic the osmolarity of serum at 290 mOsm/kg. Fragmented information on the response of hybridoma cells to elevated osmolarity is available....
Article
Full-text available
Two murine hybridoma cell lines (167.4G5.3 and S3H5/2bA2) were adapted to grow in low-serum and serum-free media by a weaning procedure. The changes in cell growth, metabolic, and antibody production rates with adaptation were examined using biochemical and flow cytometric analyses. After adaptation to a particular serum level, the short-term serum...
Article
Full-text available
A murine hybridoma cell line (167.4G5.3) was cultivated in batch mode with varying inoculum cell densities using IMDM media of varying fetal bovine serum concentrations. It was observed that maximum cell concentrations as well as the amount of monoclonal antibody attainable in batch mode were dependent on the inoculum size. Specifically, cultures w...
Article
Full-text available
Studies were conducted to determine the mechanism of drug release from pellets coated with an ethylcellulose-based pseudolatex widely accepted for use as a sustained release coating for pharmaceuticals. Possible mechanisms for release include solution/diffusion through the continuous polymer phase and/or plasticizer channels, diffusion through aque...
Article
The effects of dissolved oxygen concentration (DO) on hybridoma cell physiology were examined in a continuous stirred tank bioreactor with a murine hybridoma cell line (167.4G5.3). Dissolved oxygen concentration was varied between 0% and 100% air saturation. Cell growth and viability, carbohydrate, amino acid, and energy metabolism, oxygen uptake,...
Article
Full-text available
The quasi-equilibrium assumption is often used to simplify the analysis of reaction diffusion problems, including those that arise in drug dissolution and ionization processes. This approximation often makes the governing equations tractable, and analytical solutions may then be obtained. However, the application of the quasi-equilibrium assumption...
Article
A murine hybridoma cell line (167.4G5.3) was adapted to grow in different serum concentrations over a six month period of time. Adaptation to low serum and to serum-free media improved growth rates, but at low serum (1.25%) the antibody productivity was diminished. Flow cytometric analysis showed the presence of two distinct cell populations with r...
Article
The chemical decomposition of glutamine to ammonia and pyrrolidonecarboxylic acid was studied at 37 degrees C in a pH range of 6.8-7.8 in different media preparations containing various amounts of fetal bovine serum. The media type influenced the decomposition rate, and the first-order rate constants increased with increasing pH values. The serum c...
Thesis
Monoclonal antibodies produced by hybridoma cells are one of the most important products of biotechnology. Optimal design and development of bioreactors require a quantitative understanding of cell growth, metabolism, and antibody production rates. This thesis is a comprehensive investigation of the influence of culture environment on these biologi...
Article
Peer Reviewed http://deepblue.lib.umich.edu/bitstream/2027.42/41536/1/11095_2004_Article_306008.pdf
Article
Full-text available
This paper describes the use of a commercially available off-line gas sensing electrode for determination of ammonia and glutamine in cell culture media. The measurement technique was tested in different media preparations with different serum concentrations. The glutamine decomposition was studied as a function of pH for cell culture medium and th...
Article
Full-text available
Dynamic reaction diffusion models were used to analyze the consequences of aggregation for syntrophic reactions in methanogenic ecosystems. Flocs from a whey digestor were used to measure all model parameters under the in situ conditions of a particular defined biological system. Fermentation simulations without adjustable parameters could precisel...
Article
Full-text available
A transtubular mammalian cell perfusion chamber has been developed that allows separate delivery and control of medium and gas flow to the cells. The hydrodynamic and mass transfer characteristics of the reactor are studied experimentally for both gas and liquid components. Feasibility and potential of the transtubular reactor are demonstrated by t...
Article
Full-text available
Controlled and localized release of drugs in the intestine can be achieved by enteric coating. The design of enteric-coated tablets has so far remained empirical, in part because of the lack of a quantitative description of the drug release kinetics. In this paper, a mathematical model is presented that describes the dissolution of the polymer coat...
Article
Full-text available
The dissolution kinetics of ionizable drugs (weak acids or bases) are analyzed with a mathematical model derived from the theory of mass transfer with chemical reaction. The model assumes that the overall process is diffusion limited, that all the reactions are reversible and instantaneous, and that dissolution and reaction are limited to the stagn...
Article
The dynamics of complex systems can be effectively analyzed by judicious use of intrinsic time constants. Order of magnitude estimation based on time constants has been used successfully to examine the dynamic behavior of complicated processes. The main goal of this paper is to introduce this approach to the analysis of complex metabolic systems. T...
Article
Mathematical models have been developed for the design of bubble column slurry reactors wherein the particles with nonuniform distribution of solid reactant take part in the reaction and follow the shrinking core model. The cases of external mass transfer control, ash layer diffusion control and chemical reaction control have been analyzed using so...
Article
The influence of suspended fine particles of differing adsorbing capacity (activated carbon, avicell cellulose, SiO2, and molecular sieves) on the liquid-film mass transfer coefficient κL, was examined experimentally in a stirred cell of well-defined gas-liquid interfacial area by chemical methods. The greatest effect on κL was observed with the ac...
Article
A penetration theory analysis is presented for the problem of gas absorption, with chemical reaction involving a volatile liquid reactant. Model equations are derived and solution techniques are presented. It is shown that as long as the diffusivities of two reactants are equal, the enhancement factors predicted by film and penetration theories onl...
Article
This report is divided into two sections plus an appendix. The first section reports on computer simulations which were developed for three important coal liquefaction processes - the Mobil Methanol to Gasoline (MTG) process, the Fischer-Tropsch (F-T) process, and the synthesis of methanol. The models are designed to be general and information such...
Article
The oxidation of aqueous sodium sulphide solutions (0.13-1.00 kmol/m) by pure oxygen at atmospheric pressure was studied in a stirred cell with an unbroken interface. The temperature ranged between 278-308 K and the pH was maintained at 13 by using 0.6 kmol/m sodium hydroxide. Gas absorption rate measurements were analysed using Danckwerts' plots i...
Article
The objective of this work is to investigate areas of science and technology that have been defined as being of prime interest to coal processing technology development. These areas include properties of coal liquids and slurries, reactor design, and performance in relation to reaction mechanisms. The work comprises the following tasks: (1) reactio...

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