Modeling and control of high-throughput screening systems

2012 ◽  
Vol 20 (1) ◽  
pp. 14-23 ◽  
Author(s):  
T. Brunsch ◽  
J. Raisch ◽  
L. Hardouin
Keyword(s):  
High Throughput ◽  
High Throughput Screening ◽  
Modeling And Control ◽  
And Control ◽  
Screening Systems

scholarly journals A 96-multiplex capillary electrophoresis screening platform for product based evolution of P450 BM3

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Anna Gärtner ◽  
Anna Joëlle Ruff ◽  
Ulrich Schwaneberg
Keyword(s):  
Capillary Electrophoresis ◽  
High Throughput ◽  
High Throughput Screening ◽  
Product Formation ◽  
Resonance Spectroscopy ◽  
P450 Bm3 ◽  
Microtiter Plates ◽  
Main Challenge ◽  
Total Turnover ◽  
Screening Systems

Abstract The main challenge that prevents a broader application of directed enzyme evolution is the lack of high-throughput screening systems with universal product analytics. Most directed evolution campaigns employ screening systems based on colorimetric or fluorogenic surrogate substrates or universal quantification methods such as nuclear magnetic resonance spectroscopy or mass spectrometry, which have not been advanced to achieve a high-throughput. Capillary electrophoresis with a universal UV-based product detection is a promising analytical tool to quantify product formation. Usage of a multiplex system allows the simultaneous measurement with 96 capillaries. A 96-multiplexed capillary electrophoresis (MP-CE) enables a throughput that is comparable to traditional direct evolution campaigns employing 96-well microtiter plates. Here, we report for the first time the usage of a MP-CE system for directed P450 BM3 evolution towards increased product formation (oxidation of alpha-isophorone to 4-hydroxy-isophorone; highest reached total turnover number after evolution campaign: 7120 mol4-OH molP450−1). The MP-CE platform was 3.5-fold more efficient in identification of beneficial variants than the standard cofactor (NADPH) screening system.

Evolution inspired engineering of antibiotic biosynthesis enzymes

2017 ◽  
Vol 15 (19) ◽  
pp. 4036-4041 ◽  
Author(s):  
M. Metsä-Ketelä
Keyword(s):  
Structure Function ◽  
High Throughput ◽  
High Throughput Screening ◽  
Antibiotic Biosynthesis ◽  
Screening Systems ◽  
Proof Of Principle

Chimeragenesis is an effective tool to probe the structure/function relationships of proteins without high-throughput screening systems. Here the proof-of-principle is presented with three pairs of proteins.

High Throughput Screening for Drug Discovery and Virus Detection

2021 ◽  
Vol 24 ◽  
Author(s):  
Adetola Okea ◽  
Deniz Sahin ◽  
Xin Chen ◽  
Ying Shang
Keyword(s):  
Drug Discovery ◽  
High Throughput ◽  
High Throughput Screening ◽  
Virus Detection ◽  
Flow Time ◽  
New Drugs ◽  
Mixed Integer ◽  
General Process ◽  
Screening Systems

Background: High throughput screening systems are automated labs for the analysis of many biochemical substances in the drug discovery and virus detection process. This paper was motivated by the problem of automating testing for viruses and new drugs using high throughput screening systems. The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) at the turn of 2019-2020 presented extradentary challenges to public health. Existing approaches to test viruses and new drugs do not use optimal schedules and are not efficient. Objective: The scheduling of activities performed by various resources in a high throughput screening system affects its efficiency, throughput, operations cost, and quality of screening. This study aims to minimize the total screening (flow) time and ensure the consistency and quality of screening. Methods: This paper develops innovative mixed integer models that efficiently compute optimal schedules for screening many microplates to identify new drugs and determine whether samples contain viruses. The methods integrate job-shop and cyclic scheduling. Experiments are conducted for a drug discovery process of screening an enzymatic assay and a general process of detecting SARS-CoV-2. Results: The method developed in this article can reduce screening time by as much as 91.67%. Conclusion: The optimal schedules for high throughput screening systems greatly reduce the total flow time and can be computed efficiently to help discover new drugs and detect viruses.

scholarly journals Development and implementation of industrialized, fully automated high throughput screening systems

2003 ◽  
Vol 25 (3) ◽  
pp. 63-66
Author(s):  
Benjamin G. Carvalho
Keyword(s):  
High Throughput ◽  
High Throughput Screening ◽  
Automated Systems ◽  
Support Structure ◽  
Automation Systems ◽  
The Future ◽  
House Automation ◽  
New Generation ◽  
Screening Systems

Automation has long been a resource for high-throughput screening at Bristol-Myers Squibb. However, with growing deck sizes and decreasing time lines, a new generation of more robust, supportable automated systems was necessary for accomplishing high-throughput screening goals. Implementation of this new generation of automated systems required numerous decisions concerning hardware, software and the value of in-house automation expertise. This project has resulted in fast, flexible, industrialized automation systems with a strong in-house support structure that we believe meets our current high-throughput screening requirements and will continue to meet them well into the future.

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