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1.
Trace amounts of metals are inevitably present in biotherapeutic products. They can arise from various sources. The impact
of common formulation factors such as protein concentration, antioxidant, metal chelator concentration and type, surfactant,
pH, and contact time with stainless steel on metal leachables was investigated by a design of experiments approach. Three
major metal leachables, iron, chromium, and nickel were monitored by inductively coupled plasma-mass spectrometry. It was
observed that among all the tested factors, contact time, metal chelator concentration, and protein concentration were statistically
significant factors with higher temperature resulting in higher levels of leached metals. Within a pH range of 5.5–6.5, solution
pH played a minor role for chromium leaching at 25°C. No statistically significant difference was observed due to type of
chelator, presence of antioxidant, or surfactant. In order to optimize a biotherapeutic formulation to achieve a target drug
product shelf life with acceptable quality, each formulation component must be evaluated for its impact. 相似文献
2.
Improved Performance and Reliability of p‐i‐n Perovskite Solar Cells via Doped Metal Oxides
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Perovskite photovoltaics (PVs) have attracted attention because of their excellent power conversion efficiency (PCE). Critical issues related to large‐area PV performance, reliability, and lifetime need to be addressed. Here, it is shown that doped metal oxides can provide ideal electron selectivity, improved reliability, and stability for perovskite PVs. This study reports p‐i‐n perovskite PVs with device areas ranging from 0.09 cm2 to 0.5 cm2 incorporating a thick aluminum‐doped zinc oxide (AZO) electron selective contact with hysteresis‐free PCE of over 13% and high fill factor values in the range of 80%. AZO provides suitable energy levels for carrier selectivity, neutralizes the presence of pinholes, and provides intimate interfaces. Devices using AZO exhibit an average PCE increase of over 20% compared with the devices without AZO and maintain the high PCE for the larger area devices reported. Furthermore, the device stability of p‐i‐n perovskite solar cells under the ISOS‐D‐1 is enhanced when AZO is used, and maintains 100% of the initial PCE for over 1000 h of exposure when AZO/Au is used as the top electrode. The results indicate the importance of doped metal oxides as carrier selective contacts to achieve reliable and high‐performance long‐lived large‐area perovskite solar cells. 相似文献
3.
Eva Gefroh Art Hewig Ganesh Vedantham Megan McClure Alla Krivosheyeva Ajay Lajmi Yuefeng Lu 《Biotechnology progress》2013,29(3):672-680
(1→3)‐β‐d ‐Glucans (beta‐glucans) have been found in raw materials used in the manufacture of recombinant therapeutics. Because of their biological activity, beta‐glucans are considered process contaminants and consequently their level in the product needs to be controlled. Although beta‐glucans introduced into the cell culture process can readily be removed by bind‐and‐elute chromatography process steps, beta‐glucans can also be introduced into the purification process through raw materials containing beta‐glucans as well as leachables from filters made from cellulose. This article reports a multipronged approach to managing the beta‐glucan contamination in the downstream process. Raw material screening and selection can be used to effectively limit the level of beta‐glucan introduced into the downstream process. Placement of a cellulosic filter upstream of the last bind‐and‐elute column step or effective preuse flushing can also limit the level of contaminant introduced. More importantly, this article reports the active removal of beta‐glucan from the downstream process when necessary. It was discovered that the Posidyne® filter, a charge‐modified nylon 6,6 membrane filter, was able to effectively remove beta‐glucans from buffers at relatively low pH and salt concentrations. An approach of using low beta‐glucan buffer components combined with filtration of the buffer with a Posidyne membrane has been successfully demonstrated at preparative scale. Additionally, the feasibility of active removal of beta‐glucan from in‐process product pools by Posidyne membrane filtration has also been demonstrated. Based on the data presented, a mechanism for binding is proposed, as well as a systematic approach for sizing of the Posidyne filter. © 2013 American Institute of Chemical Engineers Biotechnol. Prog., 29:672–680, 2013 相似文献
4.
Tao Zhou Kai Chen Li-Min Kong Mu-Song Liu Yong-Min Ma Yuan-Yuan Xie Robert C. Hider 《Bioorganic & medicinal chemistry letters》2018,28(14):2504-2512
Macromolecular chelators have potential applications in the medical area, for instance, in treatment of iron overload-related disorders and in the treatment of external infections. In this investigation, several novel iron(III)-selective hydroxypyridinone hexadentate-terminated first and second generation dendrimeric chelators were synthesized using a convergent strategy. Their iron chelating ability was demonstrated by UV/Visible spectrometry and high resolution mass spectrometry (HRMS). The iron binding affinities were also investigated by the competition with a fluorescent iron chelator CP691. The result indicated that these dendrimers possesses a high affinity for iron with a very high pFe3+ value, which is close to that of an isolated hexadentate unit. These dendrimeric chelators were found to exhibit inhibitory effect on the growth of both Gram-positive and Gram-negative bacteria. 相似文献
5.
Summary The effect of shear stress on the ability of tissue factor-factor VIIa complex to activate factor X in a continuous flow reactor was studied. Tissue factor immobilized in a phospholipid bilayer on the inner surface of a capillary tube was exposed to a perfusate containing factors VIIa and X flowing at flow rates of 12.7, and 204 l/min, corresponding to wall shear rates of 100, and 1760 sec-1. The maximum flux (moles formed per unit surface area per unit time) of factor Xa (activated form of factor X) produced at the wall decreased as the shear stress at the wall was increased from 1 to 3 dynes/cm2 (3-fold) at a constant shear rate of 100 sec-1. In contrast, at higher shear rate (1760 sec-1), increasing shear stress from 16 to 48 dynes/cm2 had no significant influence on factor Xa production. The decreased production of factor Xa at higher shear stress (low shear rate 100 sec-1) probably reflects the transport limitation of factor X to the wall. Apparently shear stress can directly influence the activation of factor X at low shear rates. 相似文献
6.
Ion exchange or biosorptive processes for metalremoval generally lack specificity in metal bindingand are sensitive to ambient conditions, e.g. pH,ionic strength and the presence of metal chelators. Inthis study, cells of a genetically engineered Escherichia coli strain, JM109, which expressesmetallothionein and a Hg2+ transport system afterinduction were evaluated for their selectivity forHg2+ accumulation in the presence of sodium,magnesium, or cadmium ions and their sensitivity to pHor the presence of metal chelators during Hg2+bioaccumulation. The genetically engineered E.coli cells in suspension accumulated Hg2+effectively at low concentrations (0-20 µM) overa broad range of pH (3 to 11). The presence of 400 mMsodium chloride, 200 mM magnesium chloride, or100 µM cadmium ions did not have a significanteffect on the bioaccumulation of 5 µm Hg2+,indicating that this process is not sensitive to highionic strength and is highly selective against sodium,magnesium, or cadmium ions. Metal chelators usuallyinterfere with ion exchange or biosorptive processes.However, two common metal chelators, EDTA and citrate,had no significant effect on Hg2+ bioaccumulationby the genetically engineered strain. These resultssuggest that this E. coli strain could be usedfor selective removal of Hg2+ from waste water orfrom contaminated solutions which are resistant tocommon treatments. A second potential applicationwould be to remove Hg2+ from Hg2+-contaminated soil, sediment, or particulates bywashing them with a Hg2+ chelator andregenerating the chelator by passing the solutionthrough a reactor containing the strain. 相似文献
7.
Chantal Brämer Kimia Ekramzadeh Frank Lammers Thomas Scheper Sascha Beutel 《Biotechnology progress》2019,35(4):e2812
The natural production of patchouli oil in developing countries cannot meet the increasing demand any more. This leads to socioecological consequences, such as the use of arable land, which is actually intended for food. Hence, the world market price increased up to $150/kg. An alternative is the biotechnological production of patchouli oil using a multiproduct sesquiterpene synthase, the patchoulol synthase (PTS). Here, we report the optimization of recombinant PTS purification from Escherichia coli lysate using continuous immobilized metal affinity chromatography. First, the purification conditions of the batch process were optimized in regard to optimal buffer composition and optimized chromatographic conditions. The best purification result was achieved with Co2+-immobilized metal affinity chromatography (Sartobind® IDA 75) with a triethanolamine buffer at pH 7, 0.5 M NaCl, 10% [vol/vol] glycerol, 5 mM MgCl2 and 250 mM imidazole for product elution. This optimized method was then transferred to a continuous chromatography system using three membrane adsorber units (surface of 75 cm2 each). Within 1.5 hr in total, 4.55 mg PTS with a final purity of 98% and recovery of 68% could be gained. The purified enzyme was used to produce 126 mg/L (-)-patchoulol from farnesyl pyrophosphate. Here, for the first time bioactive PTS was successfully purified using membrane adsorbers in a continuous downstream process. 相似文献
8.
Takashi Funaki Masatoshi Yanagida Kazuyuki Kasuga Hideki Sugihara 《Inorganica chimica acta》2009,362(7):2519-407
A new type of ruthenium(II) complex containing a 2-quinolinecarboxylate ligand was designed and synthesized as a sensitizer for dye-sensitized solar cells, and its photophysical and photochemical properties were characterized. The solar cells created with this complex exhibited efficient panchromatic sensitization over the entire visible wavelength range extending into the near-IR region. An overall conversion efficiency of 8.2% was attained under standard air mass 1.5 irradiation (100 mW cm−2) with the short-circuit photocurrent density of 18.2 mA cm−2, the open-circuit photovoltage of 0.63 V and the fill factor of 0.72. 相似文献
9.
Stimulation of the (Na + + K + )-dependent adenosine triphosphatase by amino acids and phosphatidylserine: chelation of trace metal inhibitors 总被引:3,自引:0,他引:3
Amino acids stimulated the (Na+ + K+)-dependent ATPase activity of a rabbit kidney preparation without affecting the Mg2+-ATPase activity; the most effective was histidine, producing a 2-fold increase in activity. Similar stimulation was produced by the well-known chelators EDTA, EGTA, and 8-hydroxyquinoline, and by the chelating phospholipid phosphatidylserine. In the presence of maximally effective concentrations of one agent, the other agents were unable to produce additional stimulation. It is suggested that the amino acids, phosphatidylserine, and the conventional chelators all stimulate the ATPase by a common mechanism: the removal of inhibitory trace metal (s). From measurements of the metal content of the enzyme preparation and experiments with extracted reagents it was concluded that the chelatable inhibitor was in the reagents used in the incubation medium rather than being endogenous to the enzyme; attempts to identify the inhibitor (s) were unsuccessful. The chelators also stimulated the K+-dependent phosphatase activity in the preparation but had no major effect on Na+-dependent incorporation of 32P from [32P]ATP. On monovalent cation activation the chelators appeared to relieve an uncompetitive inhibition of Na32 activation and a noncompetitive inhibition of K32 activation, also suggesting an action of the chelatable inhibitor on the later stages of the ATPase reaction sequence. 相似文献
10.
Cheryl L. M. Stults Jaromir Mikl Oliver Whelehan Bradley Morrical William Duffield Lee M. Nagao 《AAPS PharmSciTech》2015,16(2):315-326
To incorporate quality by design concepts into the management of leachables, an emphasis is often put on understanding the extractable profile for the materials of construction for manufacturing disposables, container-closure, or delivery systems. Component manufacturing processes may also impact the extractable profile. An approach was developed to (1) identify critical components that may be sources of leachables, (2) enable an understanding of manufacturing process factors that affect extractable profiles, (3) determine if quantitative models can be developed that predict the effect of those key factors, and (4) evaluate the practical impact of the key factors on the product. A risk evaluation for an inhalation product identified injection molding as a key process. Designed experiments were performed to evaluate the impact of molding process parameters on the extractable profile from an ABS inhaler component. Statistical analysis of the resulting GC chromatographic profiles identified processing factors that were correlated with peak levels in the extractable profiles. The combination of statistically significant molding process parameters was different for different types of extractable compounds. ANOVA models were used to obtain optimal process settings and predict extractable levels for a selected number of compounds. The proposed paradigm may be applied to evaluate the impact of material composition and processing parameters on extractable profiles and utilized to manage product leachables early in the development process and throughout the product lifecycle.KEY WORDS: design of experiments, extractables, injection molding, leachables, process parameters, quality by design 相似文献
11.
Culbertson SM Vassilenko EI Morrison LD Ingold KU 《The Journal of biological chemistry》2003,278(40):38384-38394
The inhibition of post-Amadori advanced glycation end product (AGE) formation by three different classes of AGE inhibitors, carbonyl group traps, chelators, and radical-trapping antioxidants, challenge the current paradigms that: 1) AGE inhibitors will not increase the formation of any AGE product, 2) transition metal ions are required for oxidative formation of AGE, and 3) screening AGE inhibitors only in systems containing transition metal ions represents a valid estimate of potential in vivo mechanisms. This work also introduces a novel multifunctional AGE inhibitor, 6-dimethylaminopyridoxamine (dmaPM), designed to function as a combined carbonyl trap, metal ion chelator, and radical-trapping antioxidant. Other AGE inhibitors including pyridoxamine, aminoguanidine, o-phenylenediamine, dipyridoxylamine, and diethylenetriaminepentaacetic acid were also examined. The results during uninterrupted and interrupted ribose glycations show: 1) an unexpected increase in the yield of pentosidine in the presence of radical-trapping phenolic antioxidants such as Trolox and dmaPM, 2) significant formation of Nepsilon-carboxymethyllysine (CML) in the presence of strong chelators and phenolic antioxidants, which implies that there must be nonradical routes to CML, 3) prevention of intermolecular cross-links with radical-trapping inhibitors, and 4) that dmaPM shows excellent inhibition of AGE. Glucose glycations reveal the expected inhibition of pentosidine and CML with all compounds tested, but in a buffer free of trace metal ions the yield of CML in the presence of radical-trapping antioxidants was between the metal ion-free and metal ion-containing controls. Protein molecular weight analyses support the conclusion that Amadori decomposition pathways are constrained in the presence of metal ion chelators and radical traps. 相似文献
12.
Anxin Sun Congcong Tian Rongshan Zhuang Chen Chen Yiting Zheng Xueyun Wu Chen Tang Yuan Liu Zihao Li Beilin Ouyang Jiajun Du Ziyi Li Jingyu Cai Jinling Chen Xiling Wu Yong Hua Chun-Chao Chen 《Liver Transplantation》2024,14(8):2303941
The efficiency loss caused by area scaling is one of the key factors hindering the industrial development of perovskite solar cells. The energy loss and contact issues in the buried interface are the main reasons. Here, a new self-assembled monolayer (SAM), Ph-4PACz, with a large dipole moment (2.32 D) is obtained . It is found that Ph-4PACz with high polarity can improve the band alignment and minimize the energy loss , resulting in an open-circuit voltage (Voc) as high as 1.2 V for 1.55 eV perovskite. However, when applied to large-area devices, the fill factor (FF) still suffered from significant attenuation. Therefore, alumina nanoparticles (Al2O3-NPs) are introduced to the interface between Ph-4PACz and rough FTO substrate to further improve the flatness , resulting in a conformal perovskite film with almost no voids in the buried interface, thus promoting low exciton binding energy, fast hot-carrier extraction and low non-radiative recombination. The final devices achieved a small-area power conversion efficiency (PCE) of 25.60% and a large-area (1 cm2) PCE of 24.61% (certified at 24.48%), which represents one of the highest PCE for single device ≥ 1 cm2 area. Additionally, mini-modules and stability testing are also carried out to demonstrate the feasibility of commercialization. 相似文献
13.
Adi Prasetio Rakesh R. Pradhan Pia Dally Mohammed Ghadiyali Randi Azmi Udo Schwingenschlögl Thomas G. Allen Stefaan De Wolf 《Liver Transplantation》2024,14(9):2303705
Effective charge carrier-selective contacts are a crucial component of high-performance crystalline silicon (c-Si) solar cells. Organic materials deposited via self-assembly on the c-Si surface are promising candidates for simplified, scalable, and cost-effective processing of charge extraction layers. This study investigates the application of nPACz self-assembled monolayers (SAMs), based on carbazole and phosphonic acid groups, where n (= 2, 4, or 6) is the aliphatic chain length, to facilitate electron extraction in c-Si solar cells by tuning the work function of aluminum (Al) at the rear contact. So far, these SAM molecules are mainly applied as the hole-selective layer in state-of-the-art perovskite and organic solar cells, via anchoring on a metal oxide electrode. Here, by inserting 2PACz between amorphous silicon passivated c-Si and Al, an electron-selective contact with a contact resistivity of 65 mΩ cm2 is achieved and a power conversion efficiency of 21.4% with an open-circuit voltage of 725 mV and a fill factor of 79.2% is demonstrated. Although the 2PACz displays some instability in this study, its initial performance is comparable to those achieved with conventionally used n-type amorphous silicon. This study highlights the potential of solution-processable organic SAMs in forming carrier-selective contacts for c-Si heterojunction solar cells. 相似文献
14.
Samuel James Davidson 《Biochimica et Biophysica Acta (BBA)/General Subjects》1975,385(2):163-172
In previous studies, in vitro digestion of [1 2 5I] ribonuclease by lysosomes of mouse kidney was limited because breakdown, which was rapid at first slowed markedly so that most of the labeled protein escaped degradation. We now describe incubation conditions which allow digestion to proceed until approximately 70% of the exogenous protein label is released in acid-soluble from, after 30–45 min at 37°C. Such activity is seen with either the addition of EDTA or incubation of concentrated cell particle suspensions. EDTA is effective in low concentrations and shows the same stimulation of digestion over a range of approximately 10−6−10−3 M. Other chelating agents have similar effects; dipyridyl and hydroxquinoline are as effective as EDTA, o-phenanthroline and diethyldithiocarbamate are slightly less effective. When the incubation medium had been treated with a chelating resin, Chelex 100, dilute suspensions of lysosomes were as active as those in EDTA. These results lead to the conclusion that metal ions, present as contaminants in very small concentraions, inhibit the activity of mouse kidney lysosomes.The effect of the metal ions is to diminish lysosomal stability, leading to release of intact labeled ribonuclease in non-sedimentable form. Interaction between lysosomes and metal, leading to inhibition of digestion upon heating occurs at low temperature, but breakdown requires incubation at 37°C and may be autolytic. In contrast to chelators, mercaptoethanol is without marked effect on stability; the stimulation in digestion rate caused by this agent is due either to a direct effect on the lysosomal enzymes or to a non-destructive influence on the lysosomal structure. 相似文献
15.
Zhang Y Eric Ballard C Zheng SL Gao X Ko KC Yang H Brandt G Lou X Tai PC Lu CD Wang B 《Bioorganic & medicinal chemistry letters》2007,17(3):707-711
Maintaining a proper balance of metal concentrations is critical to the survival of bacteria. We have designed and synthesized a series of conjugates of metal chelators and efflux transporter substrates aimed at disrupting bacterial metal homeostasis to achieve bacterial killing. Biological studies showed that two of the compounds had very significant antimicrobial effect with an MIC value of 7.8 microg/mL against Gram-positive Bacillus subtilis. 相似文献
16.
Two crystalline and one highly purified galactanases were obtained from the culture broth of Bacillus subtilis var. amylosacchariticus (1043) and their chemical and enzymatic properties, especially, their specificities were comparatively studied. Their molecular weights were almost the same, but the isoelectric points were considerably different from each other. The galactanases were sensitive to metal chelators and stabilized by Ca2+. The pH optimum of the enzymes were between 6.0 and 7.0. All the galactanases investigated here attacked soybean arabinogalactan without liberation of arabinose, though they were inactive against coffee bean arabinogalactan. In digestion of soybean arabinogalactan, all the galactanases purified here formed galactose, galactobiose and galactotriose whereas the galactanase previously isolated from Bacillus subtilis K–50 produced galactobiose as the main final product. 相似文献
17.
Effect of dibutyryl cyclic AMP on the restoration of contact inhibition in tumor cells and its relationship to cell density and the cell cycle 总被引:1,自引:0,他引:1
KB cell cultures exposed to 10−4 M dibutyryl cyclic AMP were significantly inhibited and exhibited contact inhibition of growth at cell densities of 8 × 104/cm2 irrespective of the initial plating density. Control cultures reached densities of 2.5 × 105/cm2. Inhibition of growth did not occur in KB cells when the density was below 1 × 104 cells/cm2. When dibutyryl cyclic AMP was removed from KB cells in the contact-inhibited state, growth resumed with DNA synthesis beginning in about 6 h. Labeled metaphases increased rapidly after 22 h without the appearance of an early rise in unlabeled metaphases. This suggests that the inhibitory effect of dibutyryl cyclic AMP is on the G1 phase of the cell cycle. 相似文献
18.
Electrical charge on any biological surface plays a crucial role in its interaction with other molecules or surfaces. Here,
we study, under flow conditions, the interactions of erythrocytes with an artificial surface: a platinum microelectrode whose
charge density ranges from –15 to +27 μC/cm2. This artificial surface could be similar in surface charge to an endothelium or a biomaterial. In this model, interactions
are measured as a transient relative increase of the electrolyte resistance obtained by impedance measurement of a microelectrode.
A maximal interaction of erythrocytes with the charged surface is calculated in the 0 to +10 μC/cm2 charge density range. At negative surface charge, a less efficient contact was obtained because of electrostatic repulsion
forces. High positive surface charge (charge density >10 μC/cm2) does not improve the contact but induces a progressive decrease in the contact efficiency, which could be explained by a
rearrangement of macromolecules on the erythrocyte surface or an effect of positive groups on the cell membrane. This work
suggests that a greater surface area of contact is obtained in the 0 to +10 μC/cm2 charge density range and that this is provided by more molecular bridges.
Received: 23 February 1996 / Accepted: 26 April 1996 相似文献
19.
Djuro Josi? Petra Schulz Lothar Biesert Lutz Hoffer Horst Schwinn Mira Kordis-Krapez Ales Strancar 《Journal of chromatography. B, Analytical technologies in the biomedical and life sciences》1997,694(2):716
Product development and process validation are shown in the case of several products obtained from human plasma. These are virus-inactivated plasma, intravenous immunoglobulins and the clotting factors VIII and IX. Different analytical methods are presented, which are used for product control and in-process control. For the production of virus-inactivated human plasma a down-scale protocol is presented, allowing a simulation of the production on a laboratory scale. Virus validation has shown that the reduction of transfusion-relevant viruses in the process was higher than six log steps. Determination of leachables from the RP-column, which was used in this production, proved that they appear in the final product in quantities below the detection limits only. It was also shown that the chemicals used for virus inactivation could be quantitatively removed from the product. For the isolation of other products, here intravenous gamma globulins and the clotting factors VIII and IX, similar validation steps had to be taken. In the case of clotting factor VIII the following data were determined, the reduction of viruses, the amount of leachables from the column, the residues of chemicals from the solvent/detergent treatment for virus inactivation. Virus reduction was successfully performed as well as the removal of chemicals used for virus inactivation. The amount of leachables from the columns used for chromatographic purification was found to be far below the permissible levels. 相似文献
20.
Solution processed polymer:fullerene solar cells on opaque substrates have been fabricated in conventional and inverted device configurations. Opaque substrates, such as insulated steel and metal covered glass, require a transparent conducting top electrode. We demonstrate that a high conducting (900 S cm?1) PEDOT:PSS layer, deposited by a stamp‐transfer lamination technique using a PDMS stamp, in combination with an Ag grid electrode provides a proficient and versatile transparent top contact. Lamination of large size PEDOT:PSS films has been achieved on variety of surfaces resulting in ITO‐free solar cells. Power conversion efficiencies of 2.1% and 3.1% have been achieved for P3HT:PCBM layers in inverted and conventional polarity configurations, respectively. The power conversion efficiency is similar to conventional glass/ITO‐based solar cells. The high fill factor (65%) and the unaffected open‐circuit voltage that are consistently obtained in thick active layer inverted geometry devices, demonstrate that the laminated PEDOT:PSS top electrodes provide no significant potential or resistive losses. 相似文献