Lab Automation - Articles and news items
Issue 6 2012 / 18 December 2012 / Dr. Stephen Brown, Sheffield RNAi Screening Facility, Biomedical Sciences, University of Sheffield
As RNA interference (RNAi) enters its teenage years from the first critical observations, it has now reached a multi-billion pound industry. There are few research areas that have expanded as quickly and spectacularly as the field of RNAi. The potential of RNAi initially sparked a functional genomics gold rush. Different uses of this technology in genomewide screens have identified genes involved in fundamental biological processes. There are now hundreds of research papers reporting genome-wide screens using cell culture to investigate the building blocks of the cell. However tempting it may be to speculate that this technology could be the new magic bullet to all our research needs, especially after some of the previous successes, some basic aspects of the RNAi technology and screening process still need to be addressed and improved upon. This review will investigate the strengths and weaknesses of our current technology, suggesting improvements and highlighting some of the novel growth areas in this field.
Our foundations of cell biology rely upon an understanding of cellular pathways, the components of which have been investigated over the last 40 years or so. Recent embellish – ment of the pathways has been carried out using models in cell culture with RNAi technology1. Many techniques have been used to reveal the functions of core pathway proteins, but few have sparked the imagination like the RNAi screen with the potential to systematically knock down the expression of every gene in the genome. (more…)
Issue 3 2010, Past issues / 24 June 2010 / Fernando A. Ramon Olayo, Manager, GlaxoSmithKline
The pharmaceutical industry has significantly influenced laboratory automation trends in the past two decades. The need to screen large collections of chemical entities in a short time with minimised consumption of reagents has driven a strong demand of parallelisation, automation, simplification and miniaturisation solutions from the suppliers of instruments, labware and assay technologies. Currently, the levels of automation and miniaturisation seem to have reached a plateau and the new paradigms are flexibility and information content. (more…)
Issue 2 2010 / 9 May 2010 / Sheraz Gul, Vice President, European ScreeningPort GmbH
In this article, an overview regarding advances in assay formats for specific target classes and options that should be considered when considering hardware will be given. There has been a significant growth in the assay and automation technologies that are available for compound screening activities and it is essential to evaluate a variety of these before beginning a drug discovery program, the aims of these being to ensure the most relevant assay formats that are available are adopted. (more…)
Industry Focus 2010, Past issues / 22 February 2010 /
Over the past decade we have seen a significant realignment of activities associated with drug discovery and this will continue for a multitude of reasons. Within the pharmaceutical industry we have seen significant changes e.g. a decrease in the numbers of drugs that are being approved by the regulatory authorities and the looming expiration of patented drugs, both of which have an immediate and direct consequence on revenue streams. In light of these issues, the pharmaceutical industry is responding appropriately. These changes have included a re-assessment of the strategies being employed in the pre-clinical phase of drug discovery, some of which are discussed in relation to automation solutions. (more…)
Issue 6 2009, Past issues / 12 December 2009 /
Dr Gordon R Alton, Dr Scott Bowes, Dr Sheraz Gul and Chris Molloy discuss Lab Automation in this European Pharmaceutical Review roundtable discussion. (more…)
Issue 6 2009, Past issues / 12 December 2009 /
In 2010 a diverse group of scientists, engineers and professionals from around the world will come together once again for this laboratory automation event. At LabAutomation2010 participants will develop long-lasting connections through networking and expand their minds by exploring cutting-edge information and strategies. (more…)
Issue 2 2009, Past issues / 20 March 2009 /
There has been a continuous move by the large commercially orientated players involved in Drug Discovery to initiate novel methods to increase income streams and productivity. An example of the former has been the acquisition of companies and their drug pipelines and in the case of the latter, rationalisation of internal Research & Development activities. This is well illustrated by GlaxoSmithKline Pharmaceuticals which have formed small focused research units called the Centres for Excellence in Drug Discovery (CEDD) and the Discovery Performance Units (DPU) each of which having increased accountability1.
Many of the small molecule entities discovered in the pre-clinical phases of Drug Discovery have been identified from compound screening activities (CSA) e.g. Low Throughput Screening (LTS) usually employing focussed sets of compounds (numbering in the low tens of thousands) and High Throughput Screening (HTS) utilising significantly larger libraries (in the hundreds of thousands and in some cases in the region of one million compounds)2-5. These CSA require two inputs, namely an assay and high quality compound library. Up until relatively recently, most of the microtitre plate based CSA were carried out in an in vitro biochemical format that used targets in a purified form (tagged truncate or full length) prepared from recombinant expression systems. Crude preparations will also suffice, however, appropriate control experiments are required to ensure the measured modulation of target activity in the presence of compound is not due to a contaminant within the preparation. Of course, assays for transporters, ion-channels, and receptors would be in a cell membrane or cellular system. These in vitro biochemical assays tend to be a context far removed from actual physiological conditions6. More recently, human primary and stem cell based assays are becoming more common in CSA7-9. In order to enhance the outputs from these assays, High Content Screening (HCS) can also be used to yield phenotypic read-outs (e.g. changes in morphology, sub-cellular localisation and redistribution of proteins)10. The second component required for CSA, the high quality compound library, would be expected to contain known scaffolds (for LTS) or diverse chemical space (for HTS) that contain appropriate starting points for Drug Discovery. (more…)
Industry Focus 2009, Past issues / 10 January 2009 /
Among the challenges for the pharmaceutical industry, declining research productivity and increasing research costs take a prominent position. This is often put in the context of efforts in the pharmaceutical industry to automate and “industrialise” research activities, combinatorial chemistry and High Throughput Screening being the most prominent examples. An argument is being put forward that the industry replaced scientists with robots and scientists’ ingenuity with mindless screening. It is then concluded that the investments into automation were misguided and led to a decline in research productivity. (more…)
Issue 6 2008, Past issues / 3 December 2008 /
High Throughput Screening (HTS) has for many years now been playing a central role in drug discovery efforts to aid the identification of small molecule chemical entities that are capable of modifying the activity of disease relevant targets1. In order to make HTS a viable option to provide appropriate starting points for drug discovery efforts, large libraries of compounds are required that contain diverse chemical space.
These libraries are typically composed of 0.5 to 3.0 million distinct compounds in solution (usually DMSO) of which 10,000 to 100,000 are available in solid form. Subsequent to the execution of an HTS at an appropriate single concentration of compound, thousands of these are typically identified and are classified as actives. Some of these initial actives may be false positives, therefore their activities are usually confirmed in independent experiments carried out in duplicate followed by dose-response experiments to determine their potencies. The final set of confirmed actives is termed validated hits. Appropriate selectivity and liability assays enables annotation of these compounds and the most promising ones can be considered for structure-activity-relationship (SAR) studies. The SAR process is an iterative process in which new compounds are synthesised, their activities determined in appropriate assays, followed by further synthesis and compound profiling. Upon achieving the desired properties in the compound, potential starting points (lead like molecules) are obtained which would undergo a series of in-vivo validation studies. Subsequent lead optimisation could result in a pre-clinical candidate molecule which would enter a period of efficacy, safety and absorption, distribution, metabolism, excretion and toxicity (ADME-Tox)2 testing in animals and ultimately enter the various human clinical studies. The time period for a drug discovery program from its conception to initiation of human clinical trials is typically in excess of five years and consumes tens of millions of dollars. This article will overview how liquid handling technologies have aided the successful development of screening compatible assays. (more…)
Issue 6 2008, Past issues / 3 December 2008 /
Date: 24-28 January 2009
Venue: Palm Springs Convention Centre
Host: The Association for Laboratory Automation
From around the world, a diverse and highly innovative group of academicians, scientists, engineers, post-doctoral associates, graduate students, and business leaders will converge at LabAutomaton2009. The show will be held on 24-28 January 2009, at the Palm Springs Convention Centre, Palm Springs, California. (more…)
Industry Focus 2007, Past issues / 7 April 2008 /
Laboratory automation development is being increasingly outsourced to the commercial market according to a recent industrial member survey by the Association for Laboratory Automation (ALA). ALA polled 400 of its members in industry with 14 questions and received 72 responses representing 47 different companies in the Pharma, Biotech and Agriculture Science sectors (an exceptionally good response). This article discusses the four questions that pertain to how the practitioners of laboratory automation in industry get their job done.
We can compare some of these answers to historical responses to the same question by past attendees of the ‘Introduction to Laboratory Automation’ short course at the annual ALA LabAutomation. The size and diversity of the respondent pool in those cases was similar. (more…)
Industry Focus 2008, Past issues / 7 April 2008 /
The increasing need for improved efficiency, precision and 24/7 operation imply more and more sophisticated measures in laboratory automation. This is true for a variety of fields – from pharmaceutical to food, agricultural, and the petrochemical industry, as well as forensics and medical diagnostics. Chemical and biological tests have to be supported by very small individual samples in medicine and forensics, up to continuous flow production with inline quality control in the chemical industry. A vast variety of physical, chemical, and biological methods need to be supported by experiment design and control, data acquisition and evaluation, documentation as well as simulation. Time constraints, high performance, extensive resource utilisation, and reproducibility of results demand a high degree of automation including unmanned operation. Global collaborations within multinational companies are the order of the day. Regulatory compliance with its diversity of validation processes increases the complexity of tasks. In addition, laboratory automation is no longer limited to R&D or production laboratories; it is now totally integrated into almost all production systems in a globalised enterprise. Adequate automation solutions always need the expertise of domain experts and automation specialists. (more…)