Target Purity Research Articles

Effects of Ti Target Purity and Microstructure on Deposition Rate, Microstructure and Properties of Ti Films.

Three titanium (Ti) targets with different purities were used to prepare Ti films on polyimide substrates by DC magnetron sputtering. The microstructures of Ti films were characterized by a metallographic microscope, X-ray diffractometer, field emission scanning electron microscope and three-dimensional surface topography instrument. In this study, we investigated the effects of Ti target purity and microstructure on film deposition rate, surface roughness, microstructure and resistivity. The results show that the deposition rate increased with increasing Ti target purity. Ti film deposited by the high-purity (99.999%) Ti target has fewer surface particles with smaller size, lower surface roughness and lower resistivity when compared to that prepared by the Ti target of low purity (99.7%). The surface roughness of Ti film prepared by the high-purity Ti target was Sa = 121 nm, the deposition rate was 16.3 nm/min and the resistivity was 6.9 × 10−6 Ω·m. For Ti targets of the same purity, the performance of Ti film prepared by a target with equiaxed α-phase grains is better than that of Ti film prepared by a target with twins and β-phase grains.

Optimized steering: Quantum state engineering and exceptional points

The state of a quantum system may be steered towards a predesignated target state, employing a sequence of weak $\textit{blind}$ measurements (where the detector's readouts are traced out). Here we analyze the steering of a two-level system using the interplay of a system Hamiltonian and weak measurements, and show that $\textit{any}$ pure or mixed state can be targeted. We show that the optimization of such a steering protocol is underlain by the presence of Liouvillian exceptional points. More specifically, for high purity target states, optimal steering implies purely relaxational dynamics marked by a second-order exceptional point, while for low purity target states, it implies an oscillatory approach to the target state. The dynamical phase transition between these two regimes is characterized by a third-order exceptional point.

Chromatographic purification with CIMmultus™ Oligo dT increases mRNA stability

One of the major challenges of mRNA based vaccines has been their requirement for distribution and storage at extremely low temperatures, indicating that exposure of mRNA to suboptimal physico-chemical conditions can result in degradation and loss of potency; it is unclear whether this is due to instability of mRNA drug substance, or LNP-encapsulated mRNA, or both. In this study we compare the stability of model mRNA drug substance (eGFP, 995 nt) prepared by affinity chromatography with the stability of mRNA purified by precipitation. We show that both purification methods lead to highly pure mRNA drug substance, however, mRNA purified by chromatography remains stable for 28 days at 37°C, whereas mRNA purified by precipitation is subject to significant degradation under the same storage conditions. We conclude that chromatography eliminates elements and/or conditions with adverse impact on the quality of mRNA to a greater extent than precipitation method and that choosing appropriate purification strategy is crucial not only to achieve target purity but also to obtain a stable product with retained integrity.

Oxygen enrichment of air: Performance guidelines for membranes based on techno-economic assessment

The use of oxygen-enriched air (OEA) is an important strategy for reducing process cost and CO2 emissions in several industrial processes. Membrane-based processes, attributing to their high energy efficiency, are promising alternatives to cryogenic distillation and pressure-swing adsorption (PSA) at small to medium scales. However, so far, the techno-economic assessment of membrane processes has been focused on the production of low-purity O2. This study assesses O2 enrichment by membrane-based processes in a large purity range (30–95%), and reports significant energy and cost savings when high-performance membranes, marked by O2 permeance of 500–1000 GPU and O2/N2 selectivity in the range of 2–20, are developed. The analysis identifies that O2/N2 selectivities of 2–4, 6–15, and 20 are optimal for target purity of 30–40%, 50–65%, and >70%, respectively, leading to specific costs in the range of 20–50 $/tonEPO2 when blending with air is not considered. Purity target below 75% can be achieved by the single-stage process while double-stage processes are needed for higher purity targets. If highly-selective membranes are available, the cost of lower purity OEA can be further reduced by blending higher purity OEA with air.We demonstrate the benefits of the membrane process for four important applications. For natural gas combustion, optimal energy and cost savings of 41% and 22%, respectively, are predicted using membranes with selectivity of 4. An optimized hybrid system combining membrane enricher and post-combustion capture reduces energy consumption (22%) and cost (6%) with respect to the standalone capture. The production of medical-grade oxygen (90% purity) from membranes is economical (0.4 $/kL) compared to that from PSA (0.6–0.8 $/kL). Finally, 95% O2 can also be produced for oxycombustion with a specific cost of 32 $/tonEPO2.

Theoretical study of boundary instability due to internal medium perturbations

The ignition of laser-initiated inertial confined fusion (ICF) targets is still not reached, despite considerable efforts taken in this direction. The exact physical reasons for this failure are still questionable, but there are significant hints for the significant role of uncontrollable hydrodynamics instabilities, that prevent ignition. Many papers are devoted to such instabilities, special attention is paid to the Rayleigh-Taylor and Ritchmeyer–Meshkov instabilities of accelerated perturbed interfaces. In this paper we consider an alternative variant, when the interface is initially smooth and perturbations are given inside of one medium. During acceleration the perturbations are carried from medium interior to the interface even if conditions for the Rayleigh–Taylor instability are not fulfilled. This initiates the instability and mediums mixing. The effect may be important for ICF targets, where it is crucial to support target symmetry and purity of each layer during compression.

Integrated material and process evaluation of metal–organic frameworks database for energy-efficient SF[formula omitted]/N[formula omitted] separation

In this work, we proposed multi-scale screening, which employs both molecular and process-level methods, to identify high-performing MOFs for energy-efficient separation of SF6 and N2 mixture. Grand canonical Monte Carlo (GCMC) simulations were combined with ideal adsorption process simulation to computationally screen 2890 metal–organic frameworks (MOFs) for adsorptive separation of SF6/N2. More than 150 high-performing MOFs were identified based on the GCMC simulations at the pressure and vacuum swing conditions, and subsequently evaluated using the ideal adsorption process simulation. 78 out of 86 MOFs selected for the VSA conditions were able to achieve the 90% target purity level of SF6, but 62 top-performing MOFs selected for the PSA condition could not reach the purity level with a single train PSA configuration. Cascade PSA configuration was proposed and adopted to improve the purity level. We also investigated the effect of vacuum pump and compressor efficiency on the energy consumption of the process. We found that the top-performing MOFs were able to achieve the 90% purity-level of SF6 with 0.10–0.4 and 0.5–1.4 MJ per kg of SF6 for VSA and PSA processes, respectively. Finally, the process-level performance of top-performing MFOs (HKST-1, UiO-67) was evaluated on the basis of the experimental isotherms obtained from the literature, and compared with the other materials reported in the literature (MIL-100(Fe), UiO-66, and zeolite-13X). We found that the results based on the experimental isotherms are in qualitative agreement with the results based on the simulated isotherms.

Epitaxial Growth of SrMnO3 Films on SrTiO3 Substrates by Off-Axis Angle Radio Frequency Magnetron Sputtering

ABSTRACTIn this study, high-quality SrMnO3 (001) film was grown on a SrTiO3(001) substrate using a 4 N purity target by 90° off-axis RF magnetron sputtering. In this study, the influence of the plasma center and surrounding positions on the growth of the SrMnO3 film was investigated under different sputtering temperatures and working pressure conditions. The results revealed that the SrMnO3 film exhibited the best crystallinity at the sputtering center under a high working pressure (135 mTorr), high substrate temperature (750 °C), and Ar to O ratio of 1:1. After investigating the relationship between the growth rate and the working pressure through the Alpha step, the film was grown at a lower sputtering rate of 2 nm/min. X-ray diffraction confirmed that the SrMnO3 film was epitaxially grown on the SrTiO3 substrate with an orientation relationship of SrMnO3(001)//SrTiO3(001). The growth state of SrMnO3 on the crystal SrTiO3 substrate was investigated by scanning electron microscopy (SEM); the results revealed that the surface was smooth and compact. In addition, the atomic force microscopy results were consistent with the SEM result; the results revealed that the surface of the film was atomically flat, and the atomic level flatness was 0.906 nm. Furthermore, the contact angle measurement results revealed that the film and substrate surface energy were almost similar and exhibited similar adhesion and internal stress. In addition, energy-dispersive X-ray spectroscopy analysis revealed that the atomic composition ratio in the high-temperature sputtered SrMnO3 film was consistent with the stoichiometric ratio of SrMnO3. The scope and results of this study will lay a foundation on the further research of the performance of SrMnO3 film.

Experimental Design of the Multicolumn Countercurrent Solvent Gradient Purification (MCSGP) Unit for the Separation of PEGylated Proteins

The rapid growth and diffusion of biopharmaceuticals, including polyethylene glycol (PEG)–protein conjugates, required to set up stringent regulatory requirements, in terms of purity and clinical safety. In order to produce proteins that meet these requirements, the development of robust purification methods has been one of the main goals in the field of downstream processing in the last years. Most of these methods rely on single or sequential batch chromatographic separations, enabling one to reach the purity specification but often at the expense of low yield. An appealing alternative is the Multicolumn Countercurrent Solvent Gradient Purification (MCSGP). Thanks to the internal recycling of the fractions where product and impurities coelute, this process can provide a significant improvement in the process yield, preserving the purity specification. The drawback lies in the increased number of process parameters, compared to the batch, which complicates the design and optimization of this unit. In this work, we propose an ad hoc design procedure for the optimization of central-cut separations at a target purity. Using PEGylated lysozyme as a model system, we illustrate the use of this procedure to identify the load, the elution gradient as well as the collection intervals for optimal yield and productivity, at fixed purity specifications, for a batch (single) column system. The obtained optimal process parameters are subsequently transferred to the MCSGP unit. The so-designed MCSGP process exhibited superior performances compared to the corresponding optimal batch process by increasing the yield and productivity by 17.0% and 2.1%, respectively, at the purity specification of 80%.

Development of a restraining wall and screw-extractor discharge system for continuous jig separation of mixed plastics

Batch and continuous jig experiments were compared using plastic mixtures with different light and heavy particle ratios. The purity of bottom layer products of continuous jig was lower than those of batch jig because of light particle entrainment induced by the screw-type extractor. To minimize entrainment, a new discharge system consisting of a vertical restraining wall and a screw-type extractor was developed. The restraining wall was installed close to the “product-end” to separate the jig chamber into two and allow particles to transfer from one part to the other via the gap under the wall. The experimental results showed that this proposed discharge system could improve the purity of heavy particles in bottom layer products because of two reasons: (1) higher material mass ratio of heavy plastic close to product-end, and (2) changes in the flow of water and particles. Moreover, the purity of bottom layer products during continuous jig separation was influenced by the difference of material mass ratio in feed; that is, purity was higher when the ratio of heavy plastic was high. In addition, an estimation procedure based on multi-step treatment using separation curves is proposed to achieve the target purity of bottom layer products.

Rapid thermal oxidation of nano silver film for solar cell fabrication

In this paper, the nano Silver dioxides films have been deposited using the reactive pulsed laser deposition method (RPLD) using the tattoo removal Q-swithing Nd-Yag laser, at the value of the wavelength of 1064nm, pulseduration of 6 sec, and 800 mJ energy of laser have been applied for ablated an extra purity of the Silver target then deposited the nano siver oxide particles on the silicon substrates, synthesize and studying of the rapid thermal annealing (RTA) effects on the structural properties, the morphological properties, the Optical properties, the electrical properties and finally the solar cell properties for the prepared samples. Both X-ray diffraction and electron microscopy studies show that the structure of the film depends on the annealing teamperatures effects of the deposited film. The nano silver oxide is present in different crystalline stages, where the particle sizes have been increases with increasing heat treatment from 45nm to 75 nm. The analized Results of the optical aprove the improvements of the absorption lead to decreasing the reflection values compared with the surface of the silicon (crystalline Si), where the transparency for the range of larger than 300 nm and the values of the optical band gap of 2.12 eV. The synthesized results for the solar cell fabrications present a clear improvement in the solar cell quantum efficiency values in the case of silver nano oxide deposition and annealed with the high degree, where the value of the efficiency about of 4.22.

Novel Intensified Alternatives for Purification of Levulinic Acid Recovered from Lignocellulosic Biomass

The development of a bio-based economy has its foundations in the development of efficient processes to optimize biomass potential. In this context there are a multitude of molecules that can be either synthetized or recovered from biomass, among those the so-called 12 building-blocks reported by the US Department of Energy. Even if their identification and importance is clearly defined, research efforts concerning the purification or separation of these platform molecules are limited. To fill this gap, different configurations for the purification of levulinic acid recovered from lignocellulosic biomass are examined and compared in this work. In particular, hybrid configurations obtained by the combination of liquid-liquid extraction and distillation have been considered. It was demonstrated how a deep understanding of the subspace including all extraction-assisted simple column distillation configurations represents a fundamental step in the synthesis of different process alternatives. From a separation efficiency and economic standpoint, the proposed intensified liquid-liquid thermally equivalent configuration (LL-TE) and liquid-liquid side stream column configuration (LL-SSC) are promising solutions. Nonetheless, their performances are deeply interrelated to the purity target defined by the designer.

Separation and determination of ultratrace rhenium quantities in molybdenum matrix

ABSTRACT The production of very pure molybdenum, free of Re even at ultratrace levels, is extremely important in meeting target purity specifications during the production of 99Mo for medical applications. Here we propose two methods for separating ultratrace levels of Re from a bulk Mo matrix using either solvent extraction or extraction chromatography, combined with inductively coupled plasma quadrupole mass spectrometry (ICP-MS) detection. Re is extracted (D > 70) from solutions in sulfuric acid as a complex with tri-n-butyl phosphate. Scrubbing and washing steps result in total decontamination factors for Mo up to 1,700 for solvent extraction and 3,500 for extraction chromatography. Re is stripped into a 3 M NH4OH matrix and analyzed by ICP-MS. Detection (LD ) and quantification (LQ ) limits were optimized by matrix-matching to allow detection of Re in strip solutions at levels of LD = 0.1 ng Re/g-Mo and LQ = 0.3 ng Re/g-Mo in Mo powder samples. By employing these two extraction methods, excellent recoveries of Re from bulk Mo are achieved, and the LQ is improved by a factor of 5 × 104.

Effect of Polarity of Surfactant on Formation of through-Silicon Via Using Metal-Assisted Chemical Etching

In this study, we demonstrated formation of high aspect vertical holes in Si substrate using wet chemical approach, MacEtch process, for the application of through silicon via (TSV) holes. It is important that the addition of the surfactants in the etching solution to obtain the well- defined straight holes in the Si substrate using MacEtch, regardless the polarity of the surfactants. MacEtch is expected to be used for formation of TSV instead of Deep reactive ion etching (Deep-RIE) because of lower costs than Deep-RIE [1,2,3]. However, it is difficult to obtain high aspect vertical holes using MacEtch process due to its instability of etching direction for prolonged process as shown in Fig. 1(a). Addition of surfactant is usefulness to improve the morphology of etched holes. Micro scale holes were prepared in N-type Si (100) substrate using MacEtch process. The disc shape Au deposited by sputtering were used as catalyst. Before deposition of the Au catalyst, a Ti interlayer with a thickness of 10 nm was deposited directly on the Si substrate with patterned resist. The patterned Au discs (10 μm in diameter), which were deposited on a Ti / Si substrate using a photolithography lift-off process. The thicknesses of deposited Au were 10 nm for Ti/Si substrate. The base pressure of the deposition chamber was maintained at 10-5 Pa, and purity of Au and Ti target used for the deposition were 99.99 %, respectively. For the MacEtch process, a mixture of 1.0 M hydrofluoric acid (HF), 1.3 M hydrogen peroxide (H2O2) and deionized water was used as the base etching solution. Benzalkonium chloride (BKC), and polyethylene glycol (PEG), which were cationic and non-polar surfactant, respectively, were used as the additive for the etching solutions. The MacEtch of the Si substrate with patterned Au were performed for 120 min at 40 oC in the etching solution. Fig.1 shows cross sectional SEM images of typical shape of etched Si holes using MacEtch. The direction of etched Si hole was changed during MacEtch without surfactants, as shown Fig.1 (a), and these changes of direction occurred more than 60% Si holes. By contrast, we observed drastic improvement on direction of etched holes in almost all holes in addition of PEG, as indicated Fig.1 (b). Similarly, adding BKC in MacEtch process was also observed improvement. The catalyst at the bottom of substrate without surfactant was deformed and partially detached from the Si substrate, as shown Fig.1 (d). However, with PEG and BKC, the catalyst contacted to the bottom and was suppressed deformation, as indicated Fig.1 (e), (f). In addition, BKC suppressed at 25 times low concentration compared with PEG. This phenomenon was is considered due to influence of polarity of hydrogen part or structure of surfactants. Particularly, the shape of catalyst film with BKC kept flat during MacEtch process compared with PEG. Therefore, defamation of catalyst has a strong correlation with formation of bended holes. Moreover, the suppression effect of catalyst is stronger in cation, BKC, than in non-ion, PEG.

Abnormal Negative Bias Stress Instability of Amorphous InGaZnO Thin Film Transistors

The negative bias stress normally yields a negative threshold voltage shift of the thin film transistors due to the additional positive charges trapped in the gate dielectrics or at channel/gate insulator interface. However, a positive threshold voltage shift of the device with the post InGaZnO deposition annealing at 400oC is observed in our devices. The Na+ incorporation from Mo gate into the gate dielectric after 400oC annealing is responsible for this abnormal threshold voltage shift. The movement of Na+ ions toward the gate electrode by the negative gate bias decreases the distance between the gate electrode and the Na+ ions. Therefore, the voltage drop between the gate electrode and the Na+ ions reduces, and a corresponding positive threshold voltage shift is observed. Inserting a SiNx layer between the SiOx gate insulator and the Mo gate electrode can reduce the Na+ mobility, and thus a normal negative threshold voltage shift resumes. Experiment: A Mo layer with the thickness of 100 nm was sputtered on glass, and patterned as the gate electrode. Then 300 nm thick SiOx was deposited on the Mo gate electrode by plasma enhanced chemical vapor deposition (PECVD) at 350oC. A 50 nm a-IGZO active layer was sputtered on SiOx. PDA was performed with an O2/N2 gas with a mixing ratio of 1:4, and the annealing temperature is 350oC or 400oC for 1 hour. A 200 nm SiOx layer was deposited on the active layer by PECVD at 200oC as the etch-stop layer. After that, 100 nm Mo was sputtered as the source and drain electrodes. The channel width and length of all TFTs are 20μm and 10μm, respectively. Additional 100 nm thick SiOx was deposited by PECVD at 200oC as the passivation layer. Result and Discussion: The slightly negative VT shift of the device with 350oC PDA after negative bias stress (NBS) was mainly attributed to the hole-trapping in the gate insulator [1] or at the a-IGZO/gate insulator interface [2]-[3]. As the trapped holes increase, the VT shifts to the negative direction. However, the abnormally negative VT shift of the device with 400oC PDA after NBS was due to the motion of mobile Na+ in the gate insulator [4]. The Mo electrode has the Na+ concentration of ∼1×1015 cm−3, which was confirmed by second ion mass spectroscopy (SIMS). These results suggest that the origin of Na+ may be due to the contamination or the purity of Mo target. On the other hand, the peak concentration of Na+ in the device with 400oC PDA is approximately 5X of 350oC PDA. Fig. 1 shows the transfer characteristics of devices after NBS prebiased with a positive gate voltage (VGS=20V for 600 seconds). The larger positive VT shift of 400oC PDA TFT with prebias after NBS than the fresh devices is due to the large movement of Na+ toward gate electrode. Fig. 2(a) and (b) shows the band diagram to illustrate the Na+ effect. During the prebias period, Na+ near the SiOx/Mo gate electrode interface drifts toward the a-IGZO channel. When negative bias is applied at the Mo gate, Na+ moves toward the gate electrode. As the distance between Na+ and gate electrode decreases, the negative voltage drop at the gate electrode decreases, which “effectively” shifts the VT to the positive direction. In order to reduce the impact of Na+ movement, a 50nm SiNx layer was inserted between the SiOx insulator and the Mo gate electrode, and the VT shift after NBS with prebias recovered to negative direction. For SIMS measurement, the peak concentration of Na+ near SiOx and SiNx interface of the device with SiNx layer are smaller than near SiOx and Mo interface of the device without SiNx layer. On the other hand, the Na+ trapped in SiNx has low mobility and relatively low movement during NBS [5]. Therefore, the effectively positive voltage shift caused by Na+ movement is suppressed, and thus improves the reliability of 400oC PDA device. Acknowledgement: The support of INNOLUX and the Ministry of Science and Technology, Taiwan (MOST 108-2622-8-002-016, MOST 108-2218-E-002-027) is highly acknowledged.[1] Y. K. Moon et al., JJAP (2009) [2] E. N. Cho et al., Trans. Device Mater. Rel. (2011) [3] W. T. Chen et al., EDL (2011)[4] C. Lo et al., J-EDS (2016) [5] B.-D. Choi et al., JJAP (2005) Figure 1

Synthesis SnO2:Bi2O3 Nanostructure Device for Bio Sensor

SnO2:Bi2O3 colloidal NPs were synthesized by pulsed laser ablation of Sn:Bi target (50%:50%) in double distilled water (DDW) at room temperature. High purity Sn:Bi target (purity of 99.99%) was fixed at bottom of open a plastic cell containing of 2 ml DDW and DDW+ PVP which represent the liquid media. Ablation is carried out with laser operating at 1.064 nm wavelengths at flounce set in the range of 40.5J/cm2 and (60 laser pulses). The diffraction peaks in the XRD pattern broadened due to the particles in the sample are too small. The primary particle size calculated by Sherrer formula is about 150 nm. The spherical nanoparticles morphologies were carried out by scan electron microscope (SEM) analysis, exhibits spherical with average size distribution found to be 20 nm.

Isotherm parameter library and evaluation software for CO2 capture adsorbents

We developed a computer-aided evaluation software system for CO2 capture adsorbents, named General Adsorbent Library and Evaluation (GALE). This software, freely available for downloads, provides two practical functions: an extensive sorbent library with isotherm parameters for more than 2000 sorbents and a computationally efficient function to evaluation their performance for user in a pressure swing adsorption (PSA) process. The new sorbent library provides isotherm parameters, which were calculated through molecular simulations using the previously available structure libraries. Based on these parameters in the software, performances of user-selected adsorbents can be evaluated and ranked in terms of the CO2 capture efficiency in an ideal PSA process. The evaluation function is designed to address diverse situations such as varying feed conditions and target purities. Some innovative strategies regarding the use of purity upper bound and candidate pool reduction concepts are suggested to lower the computational load.

Cascade extraction of proteins and feruloylated arabinoxylans from wheat bran

A cascade process for the sequential recovery of proteins and feruloylated arabinoxylan from wheat bran is proposed, involving a protein isolation step, enzymatic destarching and subcritical water extraction. The protein isolation step combining lactic acid fermentation and cold alkaline extraction reduced the recalcitrance of wheat bran, thus improving the total yields of the subsequent subcritical water extraction. The time evolution of subcritical water extraction of feruloylated arabinoxylan was compared at two temperatures (160 °C and 180 °C). Longer residence times enhanced the purity of target feruloylated arabinoxylans, whereas higher temperatures resulted in faster extraction at the expense of significant molar mass reduction. The radical scavenging activity of the extracted feruloylated arabinoxylans was preserved after the initial protein isolation step. This study opens new possibilities for the cascade valorization of wheat bran into enriched protein and non-starch polysaccharide fractions, which show potential to be used as functional food ingredients.

N-TiO2-x Nanocatalysts: PLAL Synthesis and Photocatalytic Activity

N-TiO2-x nanocatalysts are developed by the pulsed laser ablation in liquid (PLAL) technique, a simple and surfactant-free preparation method. The PLAL approach allows synthesizing chemical-morphological fine-tuning water TiO2-based nanomaterials, starting from targets of different nature (powders and commercial high purity targets). The catalytic activity was investigated using methylene blue (cationic dye) and methyl orange (azo dye). A different photocatalytic response was found for the various kinds of N-TiO2-x. In the first 20 min, under UV and visible light, about 50% and 10% of the methyl orange were removed using the N-TiO2-x and TiO2 colloids, respectively. In addition, we observe that the response towards the methylene blue is comparable in all the synthesized samples under UV irradiation while differing by about 30% under a visible lamp. The enhanced photocatalytic response of the N-TiO2-x nanocatalysts with respect to the TiO2 one is dependent on the content of the nitrogen dopant, surface area, and nitrogen-oxygen bonding configurations.

Development of a generic reversed-phase liquid chromatography method for protein quantification using analytical quality-by-design principles

Biopharmaceutical drug substances are generally produced using fermentation technology and are subsequently purified in the following downstream process. For the determination of critical quality attributes (CQAs), such as target protein titer and purity, monitoring tools are required before quality control analysis. We herein present a novel reversed phase liquid chromatography method (RPLC), which enables facile and robust protein quantification during upstream and downstream processing of intracellularly produced proteins in E. coli.The overall goal was to develop a fast, robust and mass spectrometry compatible method which can baseline resolve and quantify each protein of interest. Method development consisted of three steps, oriented on an Analytical Quality by Design (AQbD) workflow: (i) the stationary phase as primary parameter was chosen based on state-of-the art technology thus minimizing protein on-column adsorption and providing high efficiency, (ii) secondary parameters (i.e. gradient conditions and column temperature) were optimized applying chromatographic modeling, and (iii) the established Method Operable Design Region (MODR) was challenged and confirmed during robustness testing, performed in-silico and experimentally by a Design of experiment (DoE) based approach.Finally, we validated the RPLC method for pivotal validation parameters (i.e. linearity, limit of quantification, and repeatability) and compared it for protein quantification against a well-established analytical methodology. The outcome of this study shows (i) a protocol for RPLC development using an AQbD principle for new method generation and (ii) a highly versatile RPLC method, suited for quick and straightforward recombinant protein titer measurement being applicable for the detection of a broad range of proteins.

Separation of samarium from medium rare earth mixture using multi-stage counter-current extraction

A large number of bifunctional ionic liquid extractant with ammonium-based have been formulated to separate and extract rare earth (RE) ions with better extraction efficiencies and selectivities compared to conventional extractant. In this paper, a methodical study for the separation of samarium from a mixture of samarium, europium, and gadolinium using bifunctional ionic liquid, [A336][P204] was developed. The optimum condition for the extraction was explored in regard to the concentration and type of acid as well as the organic to the aqueous ratio of the mixture. The sum of extraction and scrubbing stages are then calculated using the counter-current theory. The target purity and recovery ratio was set to 99.9% and 90%, respectively. Multi-stage of counter-current extraction process for three, four, and five stages were developed to simulate the extraction process. As a result, extraction with 3.0 M HNO3 and 4:1 organic to aqueous ratio selected as the best condition based on the value of separation factor, β: 2.81. The number of stages calculated by the theory matches the stages done experimentally, which is four. The outcome of the extraction indicates a high recovery value (>90%) but with a poor purity ratio (<70%). For scrubbing stages, by theory 13 stages is required, however in the experimental work, 18 stages needed to achieve the purity of >99%. The counter-current simulation of the samarium extraction from the mixed RE solution showed that a complete separation with excellent purity and recovery is possible and a process flow sheet has been presented.