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排序方式: 共有294条查询结果,搜索用时 15 毫秒
91.
Sanchayita Ghose Jennifer Zhang Lynn Conley Ryan Caple Kevin P. Williams Douglas Cecchini 《Biotechnology progress》2014,30(6):1335-1340
Advances in cell culture expression levels in the last two decades have resulted in monoclonal antibody titers of ≥10 g/L to be purified downstream. A high capacity capture step is crucial to prevent purification from being the bottleneck in the manufacturing process. Despite its high cost and other disadvantages, Protein A chromatography still remains the optimal choice for antibody capture due to the excellent selectivity provided by this step. A dual flow loading strategy was used in conjunction with a new generation high capacity Protein A resin to maximize binding capacity without significantly increasing processing time. Optimum conditions were established using a simple empirical Design of Experiment (DOE) based model and verified with a wide panel of antibodies. Dynamic binding capacities of >65 g/L could be achieved under these new conditions, significantly higher by more than one and half times the values that have been typically achieved with Protein A in the past. Furthermore, comparable process performance and product quality was demonstrated for the Protein A step at the increased loading. © 2014 American Institute of Chemical Engineers Biotechnol. Prog., 30:1335–1340, 2014 相似文献
92.
We studied seasonal fluctuations in the rates of photosynthesis, transpiration, PAR, and stomatal conductance for 16 species
of true mangroves from the Sundarbans region of West Bengal. Soil salinity and pH were also measured. Leaf temperatures were
almost always higher than the ambient temperature. We observed considerable seasonal (summer vs winter) as well as interspecific
variations in photosynthesis, with the highest rates occurring inHeritiera fomes (13.21 pmol m-2s-1) andAvicennia marina (11.8 mol m-2s-1), and the lowest inNypa fruticans (1.56 mol m-2s-1) andCeriops decandra (2.32 pmol m-2s-1), in many species, an abrupt rise in leaf temperature retarded the photosyn-thetic process. In winter, the rate of transpiration
and stomatal conductance reached their maxima inA. marina (4.83 mmol ra-2s-1 and 124.23 m mol m-2s-1, respectively) and their mimima inExcoecaria agallocha (1.85 mmol m-2s-1 and 49.19 mmol m-2s-1, respectively). In contrast, the maximum summer readings were recorded in E.agallocha (6.07 mmol m-2s-1 and 192.74 mmol m-2s-1 respectively). 相似文献
93.
Jennifer Zhang Lynn Conley John Pieracci Sanchayita Ghose 《Engineering in Life Science》2017,17(2):117-124
With cell culture titers and productivity increasing in the last few years, pressure has been placed on downstream purification to look at alternative strategies to meet the demand of biotech products with high dose requirements. Even when the upstream process is not continuous (perfusion based), adopting a more productive and/or continuous downstream process can be of significant advantage. Due to the recent trend in exploring continuous processing options for biomolecules, several enabling technologies have been assessed at Biogen. In this paper, we evaluate the capability of one of these technologies to streamline and improve our downstream mAb purification platform. Current conventional downstream polishing steps at Biogen are operated in flow‐through mode to achieve higher loadings while maintaining good selectivity. As titers increase, this would result in larger columns and larger intermediate product pool holding tanks. A semicontinuous downstream process linking the second and third chromatography steps in tandem can reduce/eliminate intermediate holding tanks, reduce overall processing time, and combine unit operations to reduce validation burdens. A pool‐less processing technology utilizing inline adjustment functionality was evaluated to address facility fit challenges for three high titer mAbs. Two different configurations of polishing steps were examined: (i) anion exchange and hydrophobic interaction and (ii) anion exchange and mixed mode chromatography. Initial laboratory scale proof of concept studies showed comparable performance between the batch purification process and the pool‐less process configuration. 相似文献
94.
95.
Youngbin Baek Deyu Yang Nripen Singh Abhiram Arunkumar Sanchayita Ghose Zheng Jian Li Andrew L. Zydney 《Biotechnology progress》2017,33(6):1555-1560
Diafiltration is used for final formulation of essentially all biotherapeutics. Several studies have demonstrated that buffer/excipient concentrations in the final diafiltered product can be different than that in the diafiltration buffer due to interactions between buffer species and the protein product. However, recent work in our lab has shown variations in solution pH that are largely independent of the protein concentration during the first few diavolumes. Our hypothesis is that these pH variations are due to nonidealities in the acid‐base equilibrium coefficient. A model was developed for the diafiltration process accounting for the ionic strength dependence of the pKa. Experimental results obtained using phosphate and histidine buffers were in excellent agreement with model predictions. A decrease in ionic strength leads to an increase in the pKa for the phosphate buffer, causing a shift in the solution pH, even under conditions where the initial feed and the diafiltration buffer are at the same pH. This effect could be eliminated by matching the ionic strength of the feed and diafiltration buffer. The experimental data and model provide new insights into the factors controlling the pH profile during diafiltration processes. © 2017 American Institute of Chemical Engineers Biotechnol. Prog., 33:1555–1560, 2017 相似文献
96.
Jennifer Zhang Sethu Siva Ryan Caple Sanchayita Ghose Rob Gronke 《Biotechnology progress》2017,33(3):708-715
Protein A chromatography is currently the industry gold‐standard for monoclonal antibody and Fc‐fusion protein purification. The high cost of Protein A, however, makes resin lifetime and resin reuse an important factor for process economics. Typical resin lifetime studies performed in the industry usually examine the effect of resin re‐use on binding capacity, yield, and product quality without answering the fundamental question of what is causing the decrease in performance. A two part mechanistic study was conducted in an attempt to decouple the effect of the two possible factors (resin hydrolysis and/or degradation vs. resin fouling) on column performance over lifetime of the most commonly used alkali‐stable Protein A resins (MabSelect SuRe and MabSelect SuRe LX). The change in binding capacity as a function of sodium hydroxide concentration (rate of hydrolysis), temperature, and stabilizing additives was examined. Additionally, resin extraction studies and product cycling studies were conducted to determine cleaning effectiveness (resin fouling) of various cleaning strategies. Sodium hydroxide‐based cleaning solutions were shown to be more effective at preventing resin fouling. Conversely, cold temperature and the use of stabilizing additives in conjunction with sodium hydroxide were found to be beneficial in minimizing the rate of Protein A ligand hydrolysis. An effective and robust cleaning strategy is presented here to maximize resin lifetime and thereby the number of column cycles for future manufacturing processes. © 2017 American Institute of Chemical Engineers Biotechnol. Prog., 33:708–715, 2017 相似文献
97.
Divisible load theory is a methodology involving the linear and continuous modeling of partitionable computation and communication loads for parallel processing. It adequately represents an important class of problems with applications in parallel and distributed system scheduling, various types of data processing, scientific and engineering computation, and sensor networks. Solutions are surprisingly tractable. Research in this area over the past decade is described. 相似文献
98.
Christopher Furcht Michael VanSeveren Melissa Holstein Hasin Feroz Sanchayita Ghose 《Biotechnology progress》2023,39(1):e3306
Biologics manufacturing is capital and consumable intensive with need for advanced inventory planning to account for supply chain constraints. Early-stage process design and technology transfer are often challenging due to limited information on process variability regarding bioreactor titer, process yield, and product quality. Monte Carlo (MC) methods offer a stochastic modeling approach for process optimization where probabilities of occurrence for process inputs are incorporated into a deterministic model to simulate more likely scenarios for process outputs. In this study, we explore MC simulation-based design of a monoclonal antibody downstream manufacturing process. We demonstrate that this probabilistic approach offers more representative outcomes over the conventional worst-case approach where the theoretical minimum and maximum values of each process parameter are used without consideration for their probability of occurrence. Our work demonstrates case studies on more practically sizing unit operations to improve consumable utilization, thereby reducing manufacturing costs. We also used MC simulations to minimize process cadence by constraining the number of cycles per unit operation to fit facility preferences. By factoring in process uncertainty, we have implemented MC simulation-based facility fit analyses to efficiently plan for inventory when accounting for process constraints during technology transfer from lab-scale to clinical or commercial manufacturing. 相似文献
99.
Zhenping Zhu Jaroslav Kralovec Tarunendu Ghose Molly Mammen 《Cancer immunology, immunotherapy : CII》1995,40(4):257-267
The anthracyclin antineoplastic agent doxorubicin (Adriamycin) was linked by four different methods of linkage to DalB02, an IgG1 murine monoclonal antibody (mAb) against surface-associated antigens on human chronic lymphocytic leukaemia (CLL) B cells. All the four conjugates fully retained the immunoreactivity of the parent DalB02. When the inhibitory effect of these conjugates was evaluated in vitro against the target D10–1 cells (a clone derived from an Epstein-Barr-virus-transformed human CLL B cell line that binds DalB02) it was observed that one conjugate was more potent than the free drug but the others were not. When131I-labelled unmodified DalB02 and the131I-labelled DalB02-containing conjugate that was found to be potent were injected i.v. into nude mice bearing a subcutaneous D10–1 xenograft, the percentages of the injected dose (%ID) of both131I-DalB02 and the131I-DalB02-containing conjugate that localized in the tumour were much higher than the %ID of the respective preparations that localized in normal tissues of D10–1-xenografted mice. The systemic toxicity of the conjugate was less than that of the free drug. At an equitoxic dose level, this conjugate was a more effective inhibitor of established D10–1 xenografts than the free drug.This study was supported by grants from the Medical Research Council of Canada (grant MT 10964) and the Cancer Research Society Inc., Montreal, Canada 相似文献
100.
Direct anaerobic bioconversion of cellulosic substances into ethanol by Clostridium thermocellum ATCC 27405 has been carried out at 60 degrees C and pH 7.0 (initial for 100 L) under continuous sparging of oxygen free nitrogen in a culture vessel. Raw bagasse, mild alkali-treated bagasse, and solka floc were used as substrates. The extent of conversion of raw bagasse (cellulose, 50%; hemicellulose, 25%; lignin, 19%) was observed as 52% (w/w) and 79% (w/w) in the case of mild alkali and steam-treated bagasse (cellulose, 72%; hemicellulose, 11%; lignin, 12%), respectively. Use of bagasse concentration above 10 g/L showed a decreased rate in ethanol production. An inoculum age between 28-30 h and cell mass content of 0.027-0.036 g/L (dry basis) were used. The results obtained with raw and pretreated bagasse have been compared with those of highly pure Solka Floc (hemicellulose, 10%). Studies on the product inhibition indicated a linear fall of the percent of survivors with time. An Arrhenius type correlation between the cell decay rate constant and the product concentration was predicted. Even at low levels, the inhibitory effects of products on cell viability, the specific growth rate, and extracellular cellulase enzyme were observed. 相似文献