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The Laboratory Robotics
Interest Group Mid Atlantic Chapter |
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The Laboratory Robotics Interest GroupJune 2000 MeetingThe Sixth Annual Technology Exhibition & PresentationsDate: Wednesday, June 14
Agenda: An exciting day is planned with technology exhibits and posters in the main hall. Oral Presentations will be featured in the seminar area throughout the day. Seventy eight exhibitor booths of laboratory automation hardware and software will exhibit, demonstrating their latest products and services. Extensive hors d'oeuvre, courtesy of the exhibitors, will be available as well as a cash bar. The proceeds from this exhibitor funded meeting are used to pay for various costs of running the group. In this way the LRIG can operate without collecting dues. Please support the group by attending this informative and entertaining meeting. Last year Exhibition was extremely successful with over 600 attendees and we hope to surpass that turnout. For more information contact Andy Zaayenga, [email protected]. There are rooms at the Hilton and nearby hotels for attendees who wish to stay overnight. Parking is paid for by the LRIG - the exit gate will be open when you leave. Donations for the door prize drawings are gratefully accepted. Open career positions at your company may be posted on the job board. There is no fee to attend the meeting.
Food: A highlight of the annual exhibition is the food and refreshments. From 4:00 to 6:00 PM there are buffets of vegetable crudite and cheese, as well as butler served cold and hot hors d'oeuvre. At 6:00 PM dinner is presented featuring sushi, roast beef carving board, pasta, and Middle Eastern style grilled vegetables. A cash bar is available throughout. Coffee and tea is served at 7:30 PM. The food is sponsored by all of the exhibitors - thank you!
Door Prizes:
Exhibitors
Presentations
4:00 PM Phenotype MicroArrays and companion high-throughput instruments (OmniLog?and Sprint? have been developed for testing hundreds of cell traits simultaneously. The current set of phenotypes that are tested include carbon, nitrogen, phosphorus, and sulfur sources used by the cell, biosynthesis of small molecules, and sensitivity or resistance to a wide range of drugs as well as other toxic or stimulatory chemicals. The breathing rate of the cells is measured quantitatively and kinetically as the reporter that indicates the cells' response in each well of the MicroArray. This technology can be used to determine the function of genes by doing a simultaneous comparison of a normal cell to a daughter cell in which the gene of interest is either inactivated or over-expressed. The readout of the cell detects aspects of cell function that are altered due to the genetic change (i.e. genotypic change leads to phenotypic change). Data are presented to validate this technology using strains of E. coli. Individual genes have been altered and in all cases the expected phenotypic changes, along with some unexpected phenotypic changes, were detected. Phenotype MicroArray technology can also be used to test the effects of drugs on cells to determine (a) mode of action, (b) specificity of action, and (c) interactions with other drugs.
4:25 PM The advent of higher density plate formats has presented challenges to traditional high throughput screening. There are many advantages to using higher density plates, including higher throughput, faster completion of screens, reduced use of reagents, etc. However, the smaller well and different well and atmosphere surface to volume ratios, as well as the behavior of small liquid droplets has presented some challenges to users and manufacturers of robotic systems. Some of the challenges and answers will be discussed.
4:50 PM The architecture of CLARA 2000 will be presented highlighting the key interactions between the software modules and their function. The open Driver Interface Standard will be discussed with emphasis given to its application to third party devices. A demonstration of the click-and-drag method editing, the scheduling of runs, and the run-time monitoring of a run in progress will be provided.
5:15 PM The majority of solution phase work-up traditionally involves a liquid-liquid extraction step to quench reactions and remove excess reagents. The goal of automating these procedures is to fit the requirements of the chemistry and not vice versa. This paper reports on the Automated Liquid-Liquid Extraction workstation (ALLEX) and the chemistry examples that have been performed on the system. ALLEX uses novel sensor technology to detect the boundary between two immiscible liquids and hence removes the need for any volume tracking that is required by the 'dead reckoning' approaches to automating this procedure. The sensor works by sensing electrical differences between the two solvents and then determining the cut off point to give two layers. If no boundary is detected this indicates that the sample may have formed an emulsion which is then registered in the software for later re-processing at the determination of the chemist. Three main examples will be shown; the extraction of total fats from various food samples, a library of dihydropyrimidinones prepared by a one-pot condensation and a convergent solution phase synthesis of ar-tumerone. The first example shows the use of ALLEX in a non-synthesis role in the extraction and analysis of chemicals from natural products. The automation of such procedures can lead to considerable savings in resource and increase productivity in analysis laboratories. The second example creates fluffy precipitates upon quenching of the reaction and shows the ability of the ALLEX to cope with such systems while maintaining good yield of product. It also demonstrates that by adding washing procedures between samples, the levels of cross-contamination are non-detectable by HPLC. The third example demonstrates the use of the Personal Synthesiser and ALLEX in combination to give multi-step automated solution phase reactions without complicated purification between steps. This sequence demonstrates a range of abilities of the ALLEX including the use of dense viscous solutions together with volatile ether for the lithium aluminium hydride reduction to make the alcohol. It also shows the use of saturated wash solutions such as brine for removing excess triphenylphosphine from the reaction mixture in the preparation of the chloro-compound. The versatility of ALLEX lies in the ability to handle a wide range of solvents with differing densities and viscosity with no requirements to change the procedure details. The ability to use a range of volumes (up to 20ml), without the need to volume track means that ALLEX allows true automation of extraction without the need to modify existing chemistry.
5:40 PM Dramatic advances in high-throughput screening, genomics, and combinatorial chemistry are forcing pharmaceutical companies to find new ways to coordinate, track, and integrate the process of research asset management in drug discovery. The eventual success of these technologies depends upon the integration of research asset management solutions that address the challenge of managing millions of discrete compounds. A successful research asset management solution will interface with registration, robotics and informatics systems to optimize compound and plate management processes, this leads to elimination of bottlenecks, reduced cycle time, and increased throughput.
6:05 PM Xyntek's Drug Discovery & Laboratory Automation Group offer consulting
and engineering services to address the following issues: We will present an overview of the following automation projects:
6:30 PM The precision of high-throughput quantitative data depends both on the capabilities of the laboratory automation and on the design of the assay reagents. The importance of reagent design is evident from our experience in the development of homogeneous assays for firefly luciferase. Homogeneous luciferase assays provide quantitative analysis of reporter gene expression more quickly, and with less effort than traditional assays. However, the assay design was found to substantially affect data quality and quantitative robustness. Of greatest concern is achieving uniform luminescence potential within the sample wells. We found that this could be compromised by concentration-dependence of the assay reagent, and by formation of luminescence gradients when the reagent is combined with cell culture media. To overcome these problems, we developed the Steady-Glo and Bright-Glo Reagents to minimize gradient formations when used in high-speed laboratory automation.
6:55 PM As automated screening technologies became available, the initial emphasis
was simply to get high throughput screening (HTS) systems installed and
functioning in order to increase the rate at which compounds could be screened.
A second wave of innovation has focused on miniaturization as a means of
increasing throughput while reducing costs of materials and supplies. Companies
are now working to adjust other components of the drug discovery process in
response to the rapid increase in screening capacity. ?The rate at which compounds are screened,
7:20 PM Well-designed parallel synthesis and purification technology can be applied throughout discovery and development to increase both the speed of laboratory work and the quality of results. In this presentation, we will discuss the latest developments in our parallel synthesis instrumentation and how chemists are using parallel techniques to meet new expectations for higher productivity. Included will be Trident, a modular system for library synthesis and purification, Surveyor, an automated process optimization platform and Endeavor a parallel pressurized reaction system for catalyst optimization and other gaseous reactions.
7:45 PM The twin revolutions of genomics and combinatorial chemistry have created an explosion in the number of compounds for screening. Managing these large compound libraries efficiently is a big challenge. With broad input from key industry experts, we are developing the SmartPlate Cassette, a new standard for compound management. SmartPlate is the only device which integrates shipping, storage and non-contact dispensing of sub-microliter volumes of compounds. This presentation highlights implementation examples and current performance data.
8:10 PM Over the past decade, the application of automation techniques to High Throughput Screening has made great strides. Automation has enabled HTS to increase productivity by ten-fold or more. Labs are now processing hundreds of plates per day. "A plate a minute with some automation strategies". Surprisingly enough, these advancements paid little attention to the way plates are handled before and after the actual screening process. Questions still remain about where and how to store these increased compound plates without compromising integrity. Central to the concept of plate handling up and downstream is an effective way to automatically seal and unseal a microplate. Conventional approaches such as adhesive or thermal systems have been used with various levels of success in automated systems. However, neither of these technologies can be reused, once they have been removed from the plate or pierced by awaiting pipettors. The SealTite* microplate cover is the cornerstone of a unique system that provides a reusable, fully automated sealing and unsealing technique that guarantees sample integrity under an inert gas tight seal. Used with the totally automated PlateServer Workstation, plates are retrieved from the PlateStore storage module, thawed, unsealed, logged through the barcode and delivered to any vendor's automated platform at rates up to 240 plates per hour. TekCel's new model for plate handling, storage and sealing is destined to change how microplates are automatically delivered and retrieved to various screening platforms as well as moved to long term storage. This novel approach can draw and analogy to the migration path the computer industry took in moving away from the core main frame to the client server distributed architecture. In this model data is stored and work is performed in multiple places as opposed to one large, inflexible system.
Posters
Poster: Streamlined Synthesis of
Substituted 2-Aminothiazoles Using Tandem Precipitation and Polymer-Assisted
Reactions
Poster: Complete Automation of
Nucleic Acid Purification and Analysis Reaction Setup Introducing the ABI
PRISM?6700 Automated Nucleic Acid Workstation The genomics revolution has demanded significant improvements in automation for management of nucleic acid materials. PEBiosystems developed The ABI PRISMTM 6700 Automated Nucleic Acid Workstation instrument to provide an integrated system that fully automates this historically labor-intensive task. Starting with basic biological material, such as cultured cells, the instrument performs nucleic acid purification, collects that purified material and subsequently creates the analysis plates for this material. This is accomplished in an industry standard 96 well format and has the throughput capability to process hundreds of samples per day and manages the information in an integrated database. The key to the system is the vacuum driven flow through purification tray mated with a customized vacuum station we have been able to develop a fully automated, high performance system. The principle application has been purification of cellular RNA for quantitative gene expression analysis. The proprietary protocol supports purification of very pure total cellular RNA at very consistent levels and high yield. Applications are now being developed for genomic DNA purification and for nucleic acid purification from other biological sources. In conclusion the ABI PRISM 6700 system is very efficient, cost effective solution for supporting nucleic acid analysis procedures.
Poster: LC-ARC: A NOVEL SENSITIVE
ON-LINE DETECTION SYSTEM/METHOD FOR RADIO-HPLC A novel in-line liquid chromatography radiochemical flow detection system LC-ARC (Liquid Chromatography - Accurate Radioisotope Counting) is described. The LC-ARC system consists of an existing LC system with a flow radioactivity detector, a StopFlow?controller, and a ARC?control and data acquisition software system. LC-ARC method utilizes advanced stop-flow counting technologies to accurately quantitate any desired portions of the radiochromatogram. The typical limit of detection of LC-ARC is 5-20 DPM for 14C and 10-40 DPM for 3H. The sensitivity is 10-20 fold better than that of traditional flow-through detection systems. The LC-ARC method dramatically improves the radioactivity counting accuracy and reduces the radioactive wastes. LC-ARC eliminates the need of collecting fractions for off-line counting for low level radioactivity thus reducing the study cost. LC-ARC has successfully provided an on-line sensitive detection system/method for chemists in areas where low level of radioactivity is used and highly sensitive detection method is required for radio-HPLC analyses.
Poster: Semi-Preparative High
Throughput Separations via a Parallel HPLC Configuration The desire to perform more work in less time is a constant challenge for scientists. We explored optimization of sample throughput via a single multiple probe/injector device configured with multiple chromatographs (4), employing fast HPLC separations, semi-preparative flow rates, independent fraction collection, fraction tracking and parallel analysis. With this approach, semi-preparative HPLC analysis of milligram quantities (20-40 mg range) was achieved in less than 7 minutes per set of samples, or a series of 32 semi-prep samples were chromatographed and fractionated in an hour, or 256 semi-prep samples per day. This presentation will cover key aspects of hardware strategy, system control, chromatographic performance, sample/fraction tracking and data handling.
Directions: On-line directions may be found at:
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