scholarly journals Heraeus cytomat® 6000 Series Incubators and Storage Systems from Kendro Laboratory Products

Author(s):  
Randall Engler

There are a number of cases in high throughput screening systems where a controlled environment is desired. These include incubation periods for cell-based assays, incubation for protein detection assays such as ELISA or fluorescence assays, and branching assays for mRNA detection. In addition, as the density of wells in microplates increases and well volumes become smaller, evaporation becomes a concern in all assays. The cytomat® 6000 is a robot accessible, automated CO2 incubator used for cell-based High Throughput Screening systems. The incubator provides superior environmental conditions, due to the unique access door at the back of the instrument, the PlateShuttle (see Figure 3 ). This small access opening insures that the environment inside the system (temperature, humidity and CO2) is undisturbed as microplates are accessed ( Figure 2 ). The system provides high speed, random (bar-coded) access to all microplate formats for 24, 96, 384 and 1536 well microplates (up to 261-microplate capacity). Other cytomat configurations offer refrigerated and low humidity environments.

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Anna Gärtner ◽  
Anna Joëlle Ruff ◽  
Ulrich Schwaneberg

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.


2017 ◽  
Vol 15 (19) ◽  
pp. 4036-4041 ◽  
Author(s):  
M. Metsä-Ketelä

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.


Circulation ◽  
2014 ◽  
Vol 130 (suppl_2) ◽  
Author(s):  
Jordan S Leyton-Mange ◽  
Robert W Mills ◽  
Min-Young Jang ◽  
Xaio Ling ◽  
Patrick T Ellinor ◽  
...  

Introduction: The lack of high quality predictive models for drug-induced QT prolongation continues to be a significant problem in pharmaceutical development. While human pluripotent stem cell derived-cardiomyocytes (hPSC-CMs) hold promise to be a valuable tool for drug discovery, efforts have been frustrated by the labor-intensive nature of electrophysiological recordings and the heterogeneity of hPSC-CMs populations. Methods: Using lentivirus, we introduced the genetically encoded fluorescent voltage reporter, A242-Arclight, into hPSC-CM monolayers in multi-well plates. An inverted fluorescence microscope was fit with an environmentally controlled enclosure and automated stage. High speed imaging with a Photometrics Evolve 128 EMCCD camera was performed at baseline and after administration of test compounds. Optical traces were processed using a custom program and composite AP durations, APD80, were compared before and after drug application (Figures A & B). Results: Baseline APD80 values displayed high degree of consistency between wells: 483±59 msec. High-throughput data acquisition demonstrated dose dependent APD80 increases from all QT-prolonging agents tested as well as dose dependent APD80 decrease from pinacidil. In contrast, negative control compounds caused no significant changes in APD80. Results from a representative plate are shown (Figure C). Conclusions: Optical measurements provide rapid recordings of drug-induced AP duration changes, and offer a strategy to non-invasively screen hPSC-CMs in high-throughput. Recording from cell monolayers as opposed to single cells and using paired comparisons may be beneficial in addressing the heterogeneity amongst hPSC-CM preparations.


Author(s):  
Adetola Okea ◽  
Deniz Sahin ◽  
Xin Chen ◽  
Ying Shang

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.


2003 ◽  
Vol 25 (3) ◽  
pp. 63-66
Author(s):  
Benjamin G. Carvalho

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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