ACS Chemical Information Division (CINF)
Fall, 1998 ACS National Meeting
Boston, MA (August 23-27)
SUNDAY AM / PM
Marriott Copley Place, Salon C, 4th Floor
|Interfacing Robotics and Laboratory Automation|
|R. W. Snyder, Organizer, Presiding|
Robotics, computers, and biochemistry: automation and the drug discovery process.
Marc N. Feiglin, Merck Research Labs, Rahway, NJ 07065.
Technological advances in the areas of Genetics, Combinatorial Chemistry, and High Throughput Biochemical Screening have revolutionized the drug discovery process. These technologies allow scientists to investigate more chemical entities against a larger number of biological targets in an increasingly shorter period of time. High Throughput Screening (HTS) is one area that has been tremendously affected by the introduction of computers and robotics. As automation continues to be implemented for drug screening, a typical HTS lab functions more like a factory and less like a traditional research lab. Automated systems are now involved at every stage of HTS at Merck including assay registration, sample storage, biochemical testing, data analysis, and data management. The integration of both commercial and custom in-house solutions to build a fully integrated system for HTS will be presented.
Advances in automation that make the sorting of 10,000 SPOS microreactors routine.
Anthony W. Czarnik, Vice President, Chemistry, IRORI, 11149 North Torrey Pines Road, La Jolla, CA 92037
The ability to synthesize small molecule libraries on the order of tens of thousands of members is becoming a standard job expectation in laboratories engaged in drug discovery. In addition to the obvious equipment requirements for miniaturization and chemical compatibility, the sheer numbers involved demands that reaction vessel handling become automated. Miniature radiofrequency memory tagged microreactors that are readable electronically have been developed to address this need. The movement of microreactors can occur at many stages of the split-and-pool library synthesis process. When thousands of microreactors are involved, the complete automation of these sorting requirements becomes desirable. In this talk, we will describe our reduction to practice of an automated sorter capable of moving thousands of microreactors to individual reaction vessels, removing this burden from the synthetic chemist.
Leveraging research informatics: bridging the automation information gap.
David Kniaz, 18 Campus Blvd., Newtown Square, PA 19073.
With the introduction of new technologies such as combinatorial chemistry, the number of samples being stored, tracked and retrieved has become a barrier for research. Automation can be used to exploit these compound libraries. This case study focuses on such a research facility that needed to upgrade the existing process of manually storing and retrieving its proprietary compounds in order to speed research and better manage its archive of research compounds. This was achieved through integration of a robotics system with data management software for the automated chemistry services. Automated sample management is now key to the efficient use of the vast proprietary compound libraries at the heart of high throughput screening and will provide scientists the freedom to perform the work they do best -- research.
Synthesizing robot programs from descriptions of combinatorial libraries.
David Chapman, Jonathan Handler, Afferent Systems, Inc., 2005 16th Street, San Francisco, CA 94103.
The difficulty of programming chemical synthesis robots is a significant barrier to their use. I will describe software (Afferent Synthesis) that eliminates the need for such programming, by working from an abstract description of the chemistry used to make a combinatorial library. The system is device-independent; with a suitable driver, it can be used with any synthetic instrument. Afferent Synthesis also makes it possible to interleave the synthesis of several libraries, or several batches of reaction vessels from a single large library, eliminating incubation "dead time" and increasing throughput. It provides robustness by implementing synthesis error recovery and task restart. A protocol optimization module allows the user to systematically vary conditions to find best conditions for a reaction. When coupled with other parts of the Afferent system, the software automatically generates chemical product structures, and tracks their locations.
Visual environments for collaborative drug discovery.
Christopher Ahlberg, Spotfire, Inc., 28 State Street, Suite 1100, Boston, MA 02109
The data explosion caused by modern laboratory equipment causes a fundamental problem in how researchers are to be able to cope with the flow of data. Visual environments for data exploration promises the ability for researchers to rapidly finding trends and patterns, identifying anomalies and detecting often crucial gross early errors. By taking advantage of modern graphical desktop computing power, users can perform orders of magnitude many more visual tests of data sanity - a strong advantage for example in high throughput screening and micro array analysis. The presentation will include a live demonstration of how visual discovery technology can enhance a LIMS system.
Synthesis on a chip.
Sheila H. DeWitt, William Chiang, Yue Chen, Timothy Hamilton, Sean Kelley, Jack Leber, Sterling McBride, Richard Moroney, Kerry O'Mara,
Orchid Biocomputer, Princeton, NJ 08543
Sarnoff Corporation, Princeton, NJ 08543
SmithKline Beecham, King of Prussia, PA 19406.
A microfluidic, chip-based system has been developed and used for the solid phase organic synthesis of discrete compounds in a massively parallel array. Up to 50 nmol of a single compound can be generated in each 700 nl reaction well. The use of electrohydrodynamic pumping enables the transfer of organic solutions that have little or no conductive nature, eliminates the need for mechanical valves, and provides the maximum diversity of reagent delivery for optimally designed libraries. The synthesis of up to 100 compounds on one chip employing 1-3 reaction steps has been achieved using electronic and/or pressure pumping. The results of these syntheses and issues related to the transport of solutions, reagent monitoring, and quality control of products will be presented.
Reagent selector: a new tool for high throughput synthesis.
Maurizio Bronzetti, Al J. Gushurst, Doug R. Henry, and Robert W. Snyder, MDL Information Systems, Inc., 14600 Catalina Street, San Leandro, CA 94577.
Reagent selection is one of the most critical and strategic steps in synthesis planning and library design. Availability, synthetic feasibility, structural or property similarity/dissimilarity and cost are some of the criteria that chemists use today to select reagents for a specific library synthesis. These criteria often determine the success or failure of a lead generation or optimization program. Reagent Selector is a new software tool for reagent selection. It is a bench tool created for combinatorial, medicinal, and synthetic chemists who often spend hours filtering and classifying their in-house or commercial reagent lists for synthesis. With Reagent Selector, scientists can also manage personal and sharable lists of reagents for subsequent synthesis work, create pick-lists for collection purposes, and generate purchasing lists for ordering. The program features property calculation and clustering capabilities which can be customized and expanded by the user.
Integration of informatics with a robotics synthesis laboratory.
K.I. Heuer, D. L. Flynn, J. F. Gaw, Searle Discovery Pharma IT, Monsanto Company, 4901 Searle Parkway, Skokie, IL 60077.
Combinatorial chemistry has aggressively introduced automation into the Discovery process. The use of these robotics automation tools has produced a wealth of discovery data. This presentation will describe the software tools and procedures developed to interface the chemistry and the chemist to the robotics synthesis laboratory, and manage the massive amount of data generated in the automated discovery process. Highlighted will be our Electronic Spreadsheet tool with which we capture robotics and manual synthesis steps, analytical interpretations and product yields. Also noted will be our SARplus tool which we developed to schedule different pathways of biological screens. This integration provides chemistry throughput and intelligent discovery data management.
Automating data analysis for high throughput screening.
Susan I. Bassett, John W. Elling, Bioreason, Inc., 309 Johnson Street, Santa Fe, NM 87501. g
High throughput screening yields more positive responses (hits) than can easily be analyzed manually. In addition, information is contained in the large number of negative responses from inactive molecules. Bioreason has developed a suite of automated methods that aid chemists in lead identification and optimization, using structural and physical feature information both from the hits and inactives. In our systems we use a variety of computational intelligence techniques, including traditional methods such as expert systems and statistical pattern recognition as well as neural networks and fuzzy reasoning systems. In this talk, we will present a system to automate selecting training sets directly from the screening data to be used in pharmacophore model building and QSAR analysis.
High throughput: the hidden bottlenecks.
Ron Niesen, 18 Campus Blvd., Newtown Square, PA 19073.
The frenzy is on. Any and all research organizations are putting every ounce of their efforts into building a "discovery factory." But are they destined to repeat the same learning curve as manufacturers did over the past century, or will they incorporate the best innovations of modern manufacturing into their factory approach? With the "discovery factory" as an analogy this talk will discuss the characteristics of bottlenecks, both from a technical and an organizational viewpoint. It will highlight strategies for addressing hidden ones, particularly regarding information, that can provide significant improvements to process throughput. Setting up a high throughput factory requires more than piecing equipment together. The audience will leave with a an understanding of where to focus their efforts for the most results using leading and available technologies.
MONDAY AM / PM
Marriott Copley Place Salon C, 4th Floor
Convention Center Exhibit Hall B, Plaza Level
TUESDAY AM / PM
Marriott Copley Place Salon C, 4th Floor,
Marriott Copley Place, Salon C, 4th Floor
Marriott Copley Place, Provincetown/Orleans, 4th Floor
|Materials Science Informatics:Databases for Materials Design|
|J. Rumble, Organizer, Presiding|
An integrated database approach to materials design.
John Rumble, Jr., Standard Reference Data Program, National Institute of Standards and Technology, Gaithersburg, MD 20899
During the past two decades, the advent of modern structural databases have fueled an unprecedented era of discovery in the biomedical sciences. New pharmaceuticals have be designed, biologial activity elucidated at the molecular level, and genetic coding disentangled. Today, non-organic materials science is ready for the same advances. Robust improved databases of structural information for metals, alloys and inorganic compounds are under development. These databases, combined with databases of phase equilbria and basic physical properties, hold the promise of new discoveries in surface science, catalysis, high temperature superconductors, ceramics, and alloys. This talk will review efforts to identify needed databases and how groups around the world are working to integrate together related databases so that scientists can derive the greatest benefits. Specific examples will be given from the NIST Standard Reference Data Program.
Crystallographic data for non-organic materials.
Vicky L. Karen, National Institute of Standards and Technology, Gaithersburg, Maryland 20899.
Crystallographic databases have traditionally been used as an aid to scientific research through bibliographic searching, the identification of unknown materials, and the analysis of individual crystal structures. The materials design community requires computational means to analyze, cross-correlate, and examine relationships among all data types, and is placing new demands on crystallographic data activities. To help meet these needs, NIST has extended its crystallographic data program to provide evaluated full structural data for all non-organic materials including inorganics, metals and minerals. Forthcoming products include the delivery of data items in standardized formats, the characterization of materials based on chemistry search modules, and three-dimensional visualization of structures. In addition to search, retrieval and display tools, scientific algorithms are being developed to assist information synthesis and knowledge discovery.
Surface structure data and materials design.
Philip R. Watson, Dept. of Chemistry, Oregon State University, Corvallis, OR 97331, Michel A. Van Hove, Lawrence Berkeley Lab., Berkeley, CA 94720 and Klaus Hermann, Fritz- Haber Institut, D-14195 Berlin, Germany.
The design of new materials for electronic, structural, corrosion inhibition, catalysis and other applications often hinges on a knowledge of surface, rather than bulk properties. One of the most fundamental items of surface information is a knowledge of the surface structure of a material - that is the crystallographic relationship of atoms in the surface layers of the substrate material itself and any adsorbed layers. The NIST Surface Structure Database (SSD) contains critically evaluated data for all published surface structures that contain hard information on interatomic distances and angles. Included is data on the experimental procedures, theory, 2D unit cells, 3D atomic coordinates, bond lengths and bond angles Moreover, structures can be interactively viewed and interrogated in 3D and printed/saved for later analysis. The latest version (SSD 3 .0 for PC/WIndows, available late 1998) will be demonstrated.
Computing macroscopic properties from microstructures of materials.
W. Craig Carter, Dept. of Materials Science and Engineering, Massacheusetts Institute of technology, Cambridge, MA 02139, Stephen A. Langer, NIST, Gaithersburg, MD 20899
The macroscopic properties of materials depend both on the properties of constituent materials as well as their microstructure. Microstructure involves the complex spatial arrangement of polycrystals, second phases and defects. The complex nature of microstructural data makes direct calculation of macroscopic properties a difficult task; nevertheless, many practical applications of materials depend on their precise microstructure. We have created public domain software which operates from scanned images of microstructures and allows the superposition of material properties directly onto the image. Virtual (computational) tests are then performed on the microstructural data and effective properties can be determined. Examples will be shown where thermoelastic properties of microstructures are calculated as well as reliability calculations.
Databases for advanced ceramics design and use.
Stanley Dapkunas, Ceramics Division, National Institute of Standards and Technology, Gaithersburg, MD 20899.
Excellent thermal, physical, electrical, magnetic and strength properties, good durability, and new processing methods have combined to make advanced ceramics a focal point for new engineering materials. In many cases, obtaining the desired properties for a specific material is dependent on seemingly small changes in processing, composition, and/or structure, e.g., the critical temperature of new high temperature superconductors is strongly dependent of small changes in composition. NIST is developed a suite of databases to support the design and use of advanced ceramics. The databases include data on structural and thermal properties, phase diagrams, high temperature superconductors, machining, and triboceramics. These databases and others are being integrated into a single system as the NIST Ceramics Webbook. The Ceramics Webbook also contain tools to facilitate analysis and manipulation of the data. This talk discusses the impact of the Ceramics Webbook on materials design. (http://www.ceramics.nist.gov/webbook/webbook.htm)
Materials databases for advanced performance.
David Rose, AMPTIAC, Rome, NY, 13440-6920
The Advanced Materials and Processes Technology Information Analysis Center (AMPTIAC) is one of thirteen Information Analysis Centers (IACs) funded by the Defense Technical Information Center (DTIC). AMPTIAC is responsible for maintaining the IAC's programs on metals, alloys, ceramics and composites. The demand for higher materials performance is driving efforts to consolidate and increase AMPTIAC's work in collecting and evaluating material properties. Today special attention is being paid to data on metal alloys for marine applications. Complementing the data collection and evaluation work is the development of an expert system to support materials selection for marine structures and components. Ultimately AMPTIAC plans to develop a family of property databases for many materials classes to support broad usage in advanced applications. The databases will be described in some detail with emphasis on those supporting the design of new materials.
Marriott Copley Place, Salon C, 4th Floor
Marriott Copley Place, Salon C, 4th Floor
Marriott Copley Place, Salon C, 4th Floor