High Content Screening and the Problem of Edge Effects

 By: Sinead Murphy
High content screening, or HCS, refers to the process in the biotechnology sector that focuses on using images of cells in drug discovery. Drug discovery is a hugely important part of the pharmaceutical industry and the constant quest to reach new solutions to medical problems and the search for new drugs.

Also known as cell based screening, high content screening has the advantage over 'high thoughput screening' in the level of detail possible. 'High throughput screening' is a faster method, but does not allow for the wealth of needed to understand drug effects.
The technology uses automated digital microscopy and flow cytometry. Combined with sophisticated IT systems, the technology is a powerful enabler of molecular research. Automation has resulted in the use of higher density well plates and the assay volumes have been reduced. There are clear cost savings to be made in such a strategy. However, this higher density approach can lead to environmental fluctuations between the wells and the plates.

Edge Effects
A common problem with high content screening lies in the area of 'edge effects'. Edge effects are caused by the differences between the cells at the edge and those at centre of the plates. This results in the deterioration of assay performance. In order to minimise the impact of these edge effects, laboratories and screening departments tend to avoid using the peripheral wells on plates. This is a costly exercise in that it avoids rather than solves the problem. For example, in a 96 Well Plate, 38% of the wells are at the edge of the plate and in a 384 Well Plate, 22% of the wells are at the edge of the plate.
Some of the edge effects issues are caused by:
- Fluctuations in temperature
- Osmolarity
- PH

Cell Based Assays
A microplate is a flat plate with multiple wells used as test tubes. Also known as a 'microtiter plate', or 'micro-titer' plate, the microplate is a typical tool used in testing laboratories and in analytical research generally. These are now available in a multitude of well densities, from 96 to 1536 wells per plate. A typical assay workflow for high content screening is performed with:
- cell seeding, Compound
- ligand dosing
- Fixation/Permeabilisation, washing, antibody and substrate addition

Then the images are acquired using high resolution digital imaging techniques which use multichannel fluorescent microscopy. The image analysis involves the selection and configuration of an image analysis algorithm. After that comes the data analysis and visualisation.

The next five years will see the use of the 1536 well plates. This allows for a greater number of tests to be carried out. This increasing miniaturisation saves time and also reduces the amount of reagents required. This ultimately is a key way to save costs. Biocroi's Advanced Microplate technology addresses the problem of low cell number and miniaturisation reduces the number of cells used per assay to the minimum required. Advanced Microplates technology images the entire well and captures the entire population of cells in a well.

The net effect will allow pharmaceutical companies to screen larger libraries with greater content, increasing the chances of finding good leads.
Artice Source: http://www.articlesphere.com

Related Articles in Science

People interested in the above article are also interested in the related articles listed below:

Archaeoastronomy is the study of how folks in the past accepted the phenomenon occurring in the sky, how they utilised the phenomenon and what part the sky played in the culture of these people. Archaeoastronomy can be said to be closely associated the historical astronomy. It is also related with the historic records of heavenly events which can often be used to answer astronomic Problems.
There are lots of predictions depending on which on 21st December 2012 the world will end. This date is meant to mark the end of a cycle of the Mesoamerican long count calendar which is alleged to be just about a 5125 years old cycle. Some people interpret the import of this date differently and say this date will mark the beginning of some changes and transformations.
In the sector of astronomy axial tilt is also known as obliquity. The axial tilt is generally accepted to be the angle between the rotational axis and the line vertical to the orbital plane of an object. Now Earth's axial tilt is 23.4. The orbital plane of Earth is commonly known as ecliptic plane and the there's a different name for Earth's axial tilt 'obliquity of the ecliptic'. This axis remains tilted in the same direction across the year.

More in Science

Excellent, Larry. Thank you for taking the new article directory technology and making it work to the max. I encourage everyone to keep contributing and contributing regularly. I can attest to the fact that this site is already a strong directory in a field of many. Kudos to Larry!

Matthew C. Keegan
The Article Writer


I find it a delight to use both as an author and a publisher. It is full of nice little surprises that make the whole process of writing, reading and publishing articles a complete delight. This is one that comes out tops and beats the rest hands down.

Eric Garner
Managing Director


I did a Google search and came across your site. It was exactly what I was looking for and was elated to find such a broad range of articles. As I am launching a free magazine in a small town in Florida, I wanted to be as resourceful as possible while still being able to provide some content that is interesting and well written. Your site has all the variables in the mix. Excellent Site hitting all the notes in the scale sort of speak.

Mo Montana
Florida, USA

Article Topics

Copyright © 2005 - by Larry Lim, Singapore - Article Search Engine Directory at ArticleSphere.com™
All Rights Reserved Worldwide. All Trademarks and Servicemarks are the property of the respective owners.
ArabicBulgarianCatalanChinese (Simplified)Chinese (Traditional)CzechDanishDutchEnglishEstonianFinnishFrenchGermanGreekHaitian CreoleHebrewHindiHungarianIndonesianItalianJapaneseKoreanLatvianLithuanianNorwegianPersianPolishPortugueseRomanianRussianSlovakSlovenianSpanishSwedishThaiTurkishUkranianVietnamese