Optimized Large Scale Synthesis of Phosphorothioate Oligonucleotides on PS-PEG Supports

1997 ◽  
Vol 52 (1) ◽  
pp. 110-116
Author(s):  
Michael Gerster ◽  
Martin Maier ◽  
Nils Clausen ◽  
Jens Schewitz ◽  
Ernst Bayer
Keyword(s):  
Gel Electrophoresis ◽  
Continuous Flow ◽  
Large Scale ◽  
Electrospray Mass Spectrometry ◽  
Small Scale ◽  
Batch Mode ◽  
Crucial Step ◽  
Capillary Gel Electrophoresis ◽  
Phosphoramidite Chemistry ◽  
Large Scale Synthesis

Sulphurization is a crucial step during synthesis of phosphorothioate oligonucleotides. Insufficient reaction leads to inhomogeneous products with phosphodiester defects and subsequently to destabilization of the oligomers in biological media. To achieve a maximum extent of sulphur incorporation, various sulphurizing agents have been investigated. Solely, the use of Beaucage reagent provided satisfactory results on PS-PEG supports. Based on our investigations in small scale synthesis (1 μmol) with continuous-flow technique, upscaling to the 0.1-0.25 mmolar range has been achieved using a peptide synthesizer. The syntheses were performed in batch mode with standard phosphoramidite chemistry. Additionally, large scale synthesis of a phosphodiester oligonucleotide has been carried out on PS-PEG with optimized protocols and compared to small scale synthesis on different supports. Products were analysed by 31P NMR, capillary gel electrophoresis and electrospray mass spectrometry. An extent of sulphurization of 99% and coupling effiencies of more than 99% were obtained and the products proved to have similar purity compared to small scale syntheses on CPG

The Scalability of Wet Ball Milling for The Production of Nanosuspensions

2019 ◽  
Vol 7 (2) ◽  
pp. 147-161 ◽  
Author(s):  
Maria L.A.D. Lestari ◽  
Rainer H. Müller ◽  
Jan P. Möschwitzer
Keyword(s):  
Ball Milling ◽  
Large Scale ◽  
Milling Time ◽  
High Energy ◽  
Small Scale ◽  
Particle Sizes ◽  
Scale Production ◽  
Batch Mode ◽  
Pharmaceutical Ingredients ◽  
Large Scale Production

Background: Miniaturization of nanosuspensions preparation is a necessity in order to enable proper formulation screening before nanosizing can be performed on a large scale. Ideally, the information generated at small scale is predictive for large scale production. Objective: This study was aimed to investigate the scalability when producing nanosuspensions starting from a 10 g scale of nanosuspension using low energy wet ball milling up to production scales of 120 g nanosuspension and 2 kg nanosuspension by using a standard high energy wet ball milling operated in batch mode or recirculation mode, respectively. Methods: Two different active pharmaceutical ingredients, i.e. curcumin and hesperetin, have been used in this study. The investigated factors include the milling time, milling speed, and the type of mill. Results: Comparable particle sizes of about 151 nm to 190 nm were obtained for both active pharmaceutical ingredients at the same milling time and milling speed when the drugs were processed at 10 g using low energy wet ball milling or 120 g using high energy wet ball milling in batch mode, respectively. However, an adjustment of the milling speed was needed for the 2 kg scale produced using high energy wet ball milling in recirculation mode to obtain particle sizes comparable to the small scale process. Conclusion: These results confirm in general, the scalability of wet ball milling as well as the suitability of small scale processing in order to correctly identify the most suitable formulations for large scale production using high energy milling.

Kinetics study of heterogeneous continuous-flow nitration of trifluoromethoxybenzene

2018 ◽  
Vol 3 (3) ◽  
pp. 379-387 ◽  
Author(s):  
Zhenghui Wen ◽  
Mei Yang ◽  
Shuainan Zhao ◽  
Feng Zhou ◽  
Guangwen Chen
Keyword(s):  
Continuous Flow ◽  
Kinetic Data ◽  
Large Scale ◽  
Process Development ◽  
Kinetics Study ◽  
Large Scale Synthesis

Trifluoromethoxybenzene (TFMB) nitration was studied in a microreactor, furnishing kinetic data that promoted the process development of large-scale synthesis.

Energy production and sanitation improvement using microbial fuel cells

2013 ◽  
Vol 3 (3) ◽  
pp. 383-391 ◽  
Author(s):  
I. Ieropoulos ◽  
J. Greenman ◽  
D. Lewis ◽  
O. Knoop
Keyword(s):  
Fuel Cells ◽  
Microbial Fuel Cells ◽  
Continuous Flow ◽  
Rapid Prototype ◽  
Small Scale ◽  
Anaerobic Sludge ◽  
Practical Implementation ◽  
Rapid Prototype Technology ◽  
Batch Mode ◽  
Artificial Urine

This study builds on the previous work of urine utilisation and uses small-scale microbial fuel cells (MFCs), working both as individual units in cascade or collectively as a stack, to utilise artificial urine. Artificial urine was prepared at concentrations typically found in real human urine with peptone employed as a surrogate proteinacious component. MFCs were constructed from Nanocure® polymer using rapid prototype technology. The anode and cathode electrodes were made of 15 cm2 carbon veil, folded down to fit in the 1 mL chambers. Eight MFCs were inoculated using activated anaerobic sludge; after 17 days of fed batch mode they were switched to continuous flow, initially at 0.09 mL/h and subsequently at 0.43 mL/h, resulting in HRT of 12.69 minutes/MFC. MFCs showed stable performance following the maturing period and produced, under polarisation experiments, peak power levels of 117 μW, corresponding to 962.94 W/m3. Continuous flow experiments data showed higher power production, increasing with the concentration of the carbon/energy source within artificial urine. The work demonstrates that artificial urine of varying composition can be successfully utilised for the production of energy and concomitant cleanup of organic waste. Finally, in line with the practical implementation and robotics work in our group, the small-scale MFCs were configured into a stack and directly energised electronic devices.

Large-scale synthesis of high quality InP quantum dots in a continuous flow-reactor under supercritical conditions

2015 ◽  
Vol 26 (8) ◽  
pp. 085604 ◽  
Author(s):  
Christian Ippen ◽  
Benjamin Schneider ◽  
Christopher Pries ◽  
Stefan Kröpke ◽  
Tonino Greco ◽  
...  
Keyword(s):  
Quantum Dots ◽  
Continuous Flow ◽  
Large Scale ◽  
Flow Reactor ◽  
High Quality ◽  
Supercritical Conditions ◽  
Continuous Flow Reactor ◽  
Large Scale Synthesis ◽  
Inp Quantum Dots

Small-Scale Science to Large-Scale Profession

2000 ◽  
Vol 45 (4) ◽  
pp. 396-398
Author(s):  
Roger Smith
Keyword(s):  
Large Scale ◽  
Small Scale

Development of Physics Learning Module Based on Guided Inquiry with Light Wave Material in Class XI of Senior High School

2020 ◽  
Vol 1 (1) ◽  
pp. 1-10
Author(s):  
Evi Rahmawati ◽  
Irnin Agustina Dwi Astuti ◽  
N Nurhayati
Keyword(s):  
Large Scale ◽  
Learning Strategy ◽  
Student Response ◽  
Average Score ◽  
Small Scale ◽  
Design Development ◽  
Teacher Response ◽  
Student Responses ◽  
Analysis Design ◽  
Scientific Skills

IPA Integrated is a place for students to study themselves and the surrounding environment applied in daily life. Integrated IPA Learning provides a direct experience to students through the use and development of scientific skills and attitudes. The importance of integrated IPA requires to pack learning well, integrated IPA integration with the preparation of modules combined with learning strategy can maximize the learning process in school. In SMP 209 Jakarta, the value of the integrated IPA is obtained from 34 students there are 10 students completed and 24 students are not complete because they get the value below the KKM of 68. This research is a development study with the development model of ADDIE (Analysis, Design, Development, Implementation, and Evaluation). The use of KPS-based integrated IPA modules (Science Process sSkills) on the theme of rainbow phenomenon obtained by media expert validation results with an average score of 84.38%, average material expert 82.18%, average linguist 75.37%. So the average of all aspects obtained by 80.55% is worth using and tested to students. The results of the teacher response obtained 88.69% value with excellent criteria. Student responses on a small scale acquired an average score of 85.19% with highly agreed criteria and on the large-scale student response gained a yield of 86.44% with very agreed criteria. So the module can be concluded receiving a good response by the teacher and students.

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