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Presentation October 2010: 

The State of Our Industry


Jeff W. Paslay, PhD.

Paslay Consulting

The BioPharma industry has been under increasing scrutiny over
the last decade as R&D costs continue to rise and relative
productivity has decreased. Our public image has deteriorated to a
point where we are viewed as not trustworthy and we are a constant
target of litigation. Whether these criticisms or perceptions are
just or not, is not the key issue. The real issue that many of us
ponder is “how did we get where we are today?” This presentation
will discuss some of the underlying causes for these perceptions,
actions and trends that the industry has pursued to address these
issues, and project where the industry may head to regain
productivity, efficiency and respect.

 


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Presentation June 2009: 


Considerations in Building a Compound Management Lab


Ted Peters; Compound Manager

Constellation Pharmaceuticals Inc.

The challenge of starting a compound management lab with the
limited resources of a startup company has been a unique experience.
Considerations of what is essential to the process including
storage, automated pipetting needs, technician staffing and IT
support. The focus of these consideration is to adopt new
technologies and concepts for faster screening of assay ready
plates. There is an ongoing effort to create a small scale lab with
large scale expectations of HTS and hit to lead activities. The
details at the one year mark of what has been accomplished and where
we are striving to be.

 


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Presentation June 2009: 



Bringing a Compound Collection into the 21st Century: The Introduction of
Automation and QC


Myra O’Leary;  Research Technician, Compound Management

The Broad Institute

The Broad compound management team previously worked in a fully walk up mode.
With our previous setup, throughput was limited and mistakes could go
undetected. Collaborating with HiRes Biosolutions we established a fully
automated screening center and compound management system. We also implemented
quality control by LC/MS throughout our entire existing collection creating
thresholds for compound quality. Details of our current compound management
system include increased throughput, improved automation capabilities and
compound quality, and novel informatics tools and a bright outlook for our
future.

 


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Presentation June 2009: 
Progressive Compound
Management: Strategies and Pitfalls


Rhett L. Affleck, Ph. D.; V.P. Technology

Nexus Biosystems

 


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Presentation April 2009: 

The cancer Biomedical Informatics Grid®
(caBIG®): Resources to support
translational research


Donna Messersmith, PhD; Integrative Cancer Research Product
Representative

National Cancer Institute – Center for Bioinformatics and Information Technology

caBIG® is an NCI Initiative to establish
a virtual network of organizations developing and adopting interoperable
databases and analytical tools to facilitate translational cancer research. It
is an open-source, open-access program, and all the tools and resources are
freely available for the research community. Mature tools have been bundled into
the Life Sciences Distribution and Clinical Trials Management Suite.

The Life Sciences Distribution includes tools that allow management
and annotation of microarray data (caArray), biospecimens (caTissue), clinical
information (CTODS), in vivo images (NCIA), genome-wide association studies (caGWAS),
as well as integrated analysis and annotation of sequence and expression data (geWorkbench).
All the LSD tools are connected to caGrid, which makes it possible for the
databases at multiple institutions to be interconnected to support data sharing
and integration.

The Clinical Trials Management Suite is a comprehensive set of modular
and interoperable tools to support the management of study participant
information through the clinical trial lifecycle. The Suite enables management
of tasks such as: screening and registering patients for accrual to clinical
trials; scheduling and tracking of patient encounters during the course of a
study; integrating laboratory results with the patient record; tracking and
managing adverse events; capturing, storing, analyzing and routing clinical data
in a meaningful manner.

More information on caBIG® is available
at https://cabig.nci.nih.gov/.

Presented at LRIG Mid Atlantic,
Automated Biorepositories: Enabling
Technologies


 


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Presentation April 2009:
 

Biospecimen Research Database (BRD)


Andrew Breychak, PhD; Biospecimen Research Database (BRD)
Representative

National Cancer Institute – Center for Bioinformatics and Information Technology

The Biospecimen Research Database (BRD) is designed to address the
problem of no reliable means to find well vetted, sufficiently
expressed experimental protocols for creating biospecimens. This
affects researchers in terms of the time to search for and find a
relevant protocol to utilize. If one is not found then additional
time and effort is required to develop their protocol. The impact of
a solution would be to expedite scientific research. The ideal
solution would be to provide a searchable, well-documented means to
prepare a repeatable and consistent biospecimen through a curated
protocol.

The BRD addresses this need by promoting the idea that data about
biospecimen protocols should be structured in a way to allow easy
search and use. Papers and studies are curated to identify
technology platform, analyte, and biospecimen location. As the
curated quantities that represent best practices increases the BRD
will become a preferred starting point to find well annotated
protocols. This will give rise to Standard Operating Protocols
(SOPs) built from the meta-analysis of biospecimen protocols. By
posting published SOPs in the BRD and making them searchable
entities with the characteristics of being digitally unique,
versioned, able to be referenced, and portable the BRD will fulfill
part of the mission of the Office of Biorepositories and Biospecimen
Research (OBBR).

Presented at LRIG Mid Atlantic,
Automated Biorepositories: Enabling
Technologies


 


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Presentation April 2009: 
Mixed phase 21st century, world class biobanking story

Steve Arsenault, directeur de l’exploitation

Biobanque Génome Québec

Challenges of implementing a world class Biobank

Building a public resource: The Genome Quebec – Centre hospitalier affilié
universitaire régional de Chicoutimi Biobank

Evaluating and choosing a cost-effective and sustainable infrastructure

Implementation Process and Timeline

Current Biobank Operations

Presented at LRIG Mid Atlantic,
Automated Biorepositories: Enabling
Technologies


 


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Presentation April 2009: 
DNA Extraction Technology Overview – Increasing Capacity 10X

Robert J.Corr

Pfizer Global
Research & Development, DNA & BioFluids Center of Emphasis, Pfizer Inc., Kings
Heights, Groton, CT

New protocols, extensive multiplexing, increased sensitivity of detection,
and advances in miniaturization and automation have substantially reduced the
amount of DNA required for downstream assays prompted the question: are we
banking an appropriate amount of DNA?

The current DNA extraction platform at the DNA & BioFluids CoE was designed to
extract large quantities of DNA from large volumes of human whole blood. After
discussions with our colleagues in Exploratory Research, it was determined that
decreasing banked DNA amounts while increasing throughput was preferable to the
current model. This presentation describes the process of reviewing the current
technology landscape with the intent of increasing daily DNA extraction capacity
by ten fold while maintaining quality and reducing operating cost. The
exploration of the technology landscape included the review of chemistry
(solid-phase, precipitation, silica, and magnetic bead technologies) and various
automation options. Additionally, in-house and outsourcing processing costs were
compared.

Presented at LRIG Mid Atlantic,
Automated Biorepositories: Enabling
Technologies


 


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Presentation April 2009: 

Development of QC methods to monitor cross-contamination from
fixed-tip automation used to extract DNA from clinical blood samples


Stephanie K. Hall1, Jason Harraden2
and Diane L. Johnson2

Pfizer Global Research & Development, 1Groton
Laboratories, Pfizer Inc., Groton, CT 06340 2DNA/Biofluids
BioBank, Pfizer Inc., Kings Heights, Groton, CT 06340

Clinical studies and gene-based target discovery require high quality DNA for
genotyping, genetic association studies and resequencing efforts. Rigorous
quality control (QC) procedures are required to assess the DNA extracted from
our automated DNA extraction process to ensure high standards and sample
integrity for the material used in our studies. Our DNA extraction process uses
fixed-tip automation which could increase the potential of sample contamination.
The QC procedures that have been developed to monitor cross-contamination will
be discussed in our presentation.

Evaluating samples for cross contamination using water control samples is a
critical step in our QC methodology. TaqMan genotyping assays were used
initially to evaluate water samples from our DNA extraction process.
Cross-contamination rates approaching 20% were detected in early development of
the DNA extraction process. Enhanced tip washing procedures were implemented in
addition to a tip bleaching step. These modifications significantly reduced
observed cross-contamination levels to <2%. One limitation of the TaqMan assay
is its inability to precisely quantitate the contamination that was detected.
Copy number and plus/minus real-time PCR assays were developed and used with
serially diluted DNA of known concentration to provide absolute quantitation of
contamination levels. Using these assays, we have been able to detect
contamination at levels of 1 pg/ul. A mixing experiment was performed to assess
whether low level system contamination could alter the performance of extracted
DNA samples in genotyping assays. A contaminated water sample from an individual
homozygous for one SNP allele was combined in equal proportion with DNA from an
individual homozygous for the other SNP allele. TaqMan genotyping assays were
performed and no alteration in the genotype of the DNA sample was observed. The
genotypes were always reflective of the DNA allele and were not affected by the
presence of contamination from the combined water sample. Future enhancements
are being developed to provide QC methods to evaluate clinical DNA samples
extracted on our automated system.

Presented at LRIG Mid Atlantic,
Automated Biorepositories: Enabling
Technologies


 


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Presentation 2/08:  
ISBER (also available as PDF)

Dr. David Toke, Associate Managing Director, Rutgers University Cell &
DNA Repository (RUCDR)


ISBER is the leading international forum
that addresses the technical, legal, ethical, and managerial issues relevant to
repositories of biological and environmental specimens. Dr. Toke will present a
brief overview of ISBER; including advantages of membership, corporate sponsors,
Best Practices 2nd Edition, and the
annual meeting in May at
Bethesda.

Presented at LRIG Mid Atlantic,
Automated Biorepositories:
Successful Models


 


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Presentation 2/08: 
Development and validation of the UK Biobank sample handling,
processing and archiving protocol

(also available as PDF)

Tim Peakman, Executive Director, UK Biobank

UK Biobank is a large prospective study established in the United Kingdom to
determine the role of genetic factors, environmental exposures and lifestyle in
the causes of major diseases of late and middle age. Extensive data and
biological samples are being collected from 500,000 participants aged between 40
and 69 years. Which biological samples are collected and how they are processed
and stored will have a major impact on the future value of the UK Biobank
resource. The UK Biobank sample handling and storage protocol has been carefully
designed to future proof the study (i.e. to avoid, as far as can be predicted,
processing or storage approaches that will preclude current or future assays)
and to provide a resource that would give the maximum scientific value within
the available budget. The protocol was developed through a thorough review of
the literature on sample handling and processing as well as wide consultation
within the academic community. This approach addressed issues such as which
samples should be collected, how and when they should be processed, and how the
processed samples should be stored to ensure their long term integrity. The
factors involved in developing the final protocol will be discussed. The
recommended protocol was also extensively tested in a series of pilot studies
conducted by collaborating groups throughout the UK. Using a variety of
technologies to assay the genome, transcriptome, proteome and metabolome, these
studies examined the stability of a wide range of components of blood and urine
maintained at either 4ºC or 18ºC
for varying times prior to processing and cryopreservation. An overview of the
results of these pilots will be presented. The sample processing and archiving
protocol adopted by UK Biobank provides a feasible approach to quality and
throughput that reflects the size and aims of the project within the available
funding.

Note: The full validation studies with all the data are
going to be published in the April edition of
International Journal of
Epidemiology
as a main paper and a special supplement.

Presented at LRIG Mid Atlantic,
Automated Biorepositories:
Successful Models


 


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Presentation 2/08: 
Implementation of the UK Biobank (also available as PDF)

Paul Downey, Director of Operations, UK Biobank

UK Biobank is a new organisation, set up to facilitate efficient medical and
scientific research. The project will recruit 500,000 volunteer members of the
public over a period of three years. The volunteers provide detailed information
about the health and lifestyle and consent to access to their health care
records. This will form a valuable resource that can be rapidly accessed by
research organisations.

In order to deliver the project, a national network of recruitment clinics
has been established to receive and process the volunteer participants. A
biological specimen processing factory has been constructed and an automated
biological specimen repository developed, having the capacity to process and
store the 14,000,000 sample aliquots that will be created.

The use and delivered benefits of utilising modern manufacturing practices to
design implement and operate a sample processing facility will be discussed. The
use of appropriate techniques during the evolving phases of the project: the
research and design phase, the operations development phase and the operational
phase will be covered. Selection and implementing appropriate culture and
quality systems at the phases of the project to support the organisational
objectives will be discussed.

Presented at LRIG Mid Atlantic,
Automated Biorepositories:
Successful Models


 


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Presentation 2/08:  
The Pfizer Liquid Store, DNA & BioFluids REMP Store
(also available as PDF)

Craig Hines, Manager, Liquid Store Center of Emphasis, Pfizer – Kings
Heights Technology Center

Diane Johnson, Head of DNA & BioFluids Center of Emphasis, Pfizer – Kings
Heights Technology Center

Leonid Vodonos, Facility Manager, Pfizer – Kings Heights Technology Center

This presentation will discuss the Kings Heights Technology Center scientific
business objectives in conjunction with the facility support infrastructure and
operational service delivery model. The presenters will provide details of the
unique relationship between the Kings Heights Scientific Lines and Global
Operations that laid foundation for a dynamic and State-of-the-Art technological
facility.

Recently Global Operations has collaboratively developed and implemented a
wide variety of business specific services including Processing Labs humidity
control, management of service contracts based on contractual partnership,
scheduling and coordination of preventative maintenance, demand repair work,
handling service related documentation, Facility Center asset management, 24/7
monitoring and equipment emergency response, production process consumable
supply/tracking and lab support technical services. Global Operations has made a
commitment to deliver cost-effective services and solutions that enhance
scientific productivity.

The timelines for design, manufacture, and installation of the REMP Stores
will be presented. As well as a number of functionalities that was developed for
the Liquid Store, DNA & BioFluids REMP store & laboratories.

Presented at LRIG Mid Atlantic,
Automated Biorepositories:
Successful Models


 


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Presentation 2/08:  The
Rutgers University Cell and DNA Repository
(also available as PDF)

Dr. Andrew Brooks, Associate Director of Technology Development for the
Rutgers University Cell and DNA Repository (RUCDR)

The Rutgers University Cell and DNA Repository (RUCDR) is among the largest
academic repositories in the world. The scope of the repository grows every year
and includes service offerings that range from DNA extraction to cell line
immortalization in addition to a considerable sample distribution program.
Currently the RUCDR maintains several large federal respoitories for the
following NIH institutes: NIAAA, NIDA, NIMH and NIDDK. Additionally, the RUCDR
services several foundation projects that include and are not limited to the
Simons Autism Foundation and the New Jersey Tourettes collection. In total the
RUCDR currently manages over 60 different clinically based projects through
these and other agencies which help geneticists around the world understand the
genetic basis for over 25 different diseases. In order to coordinate the
collection and processing of samples from over 400 collection sites worldwide
and manage over 1 million cell line aliquots and 750,000 samples in mechanical
storage the RUCDR has developed several sophisticated automation schemes to
handle many aspects of the RUCDR workflow. The structure of the RUCDR, a
description of its automation infrastructure and a detailed overview of the
programs services will be discussed.

Presented at LRIG Mid Atlantic,
Automated Biorepositories:
Successful Models


 


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Presentation 1/07:  
Shared
Materials Repositories at the Harvard Institute of Proteomics
(also available as PDF)

Stephanie Mohr, Ph.D.; Manager, PSI Materials Repository

Harvard Institute of Proteomics, Harvard Medical School




The Harvard Institute of Proteomics (HIP) hosts the DF/HCC DNA
Resource Core plasmid repository, which has a collection of more
than 30,000 plasmid clones that are stored, maintained and
distributed at HIP. In addition, HIP was recently awarded a
five-year, multimillion dollar grant from the NIGMS division of NIH
to host a similar plasmid repository for the Protein Structure
Initiative, a consortia group of researchers at several institutions
who have generated more than 65,000 plasmid clones as part of their
efforts to resolve the 3D structures of diverse proteins. At HIP,
plasmid clone samples are transformed into phage-resistant bacterial
host strains, single-colony selected and used to create glycerol
stocks in a highly automated, highly quality-controlled manner.
Plasmid clone samples are then stored at -80 degrees C in
individually barcode-labeled tubes in a state-of-the-art automated
freezer storage system, the BioBank (Thermo/Zmation) and back-up
samples are stored in standard freezers. Plasmid clone information
(vector info, insert info, growth conditions, etc.) is carefully
curated and stored in our custom Plasmid Information Database (PlasmID;

http://plasmid.hms.harvard.edu
). Standard operating procedures
for clone intake, sequence validation, storage, maintenance and
distribution of plasmid clones will be discussed.



Presented at LRIG Mid Atlantic,
Biorepositories: An
Automation Frontier


 

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Presentation 1/07:  

The Repository for the International HapMap Project
(also available as PDF)

Donald L. Coppock, Ph.D.; Assistant Director

Coriell Cell Repositories, Coriell Institute for Medical Research




The International HapMap Project was established to create a
resource for genetics research to make it possible to speed the
identification of genes for diseases. The goal is to create a map of
human variation by identifying single nucleotide polymorphisms (SNPs)
in a number of populations from around the world. Coriell has
provided the repository for these samples. In total there are 1,200
cell lines in the Repository. The Coriell approach to establishing
this Repository will be described including interactions with the
donor communities, establishment of cell lines, preparation of DNA,
distribution of samples and handling the extensive data connected to
the samples. Lastly, the possibility of automation of the Repository
will be discussed in relation to the HapMap Repository.



Presented at LRIG Mid Atlantic,
Biorepositories: An
Automation Frontier


 

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Presentation 1/07:  
NCI’s
Recent Initiatives in Biospecimen Research and Policy
(also available as PDF)


Jim Vaught, Ph.D.; Special
Assistant for Biorepository Science

Division of Cancer Epidemiology and Genetics

National Cancer Institute

Recognizing that biospecimen
resources are crucial to the research community, the National Cancer
Institute (NCI) established the Office of Biorepositories and
Biospecimen Research (OBBR)in 2005. One of the goals of the OBBR is
to unify policies and procedures for NCI-supported biospecimen
resources. In early 2006 NCI released the First-Generation
Guidelines for NCI-Supported Biospecimen Resources. The Guidelines
include recommendations for biorepository technical and operational
activities, informed consent, informatics, intellectual property and
specimen custodianship. Future editions of the Guidelines will
include revisions based on new NCI-OBBR initiatives in biospecimen
research. Among other strategic initiatives the OBBR will also
evaluate new technologies to improve the overall quality of
biospecimens as well as to enhance the efficiency of collection,
processing and storage of biospecimens for research.



Presented at LRIG Mid Atlantic,
Biorepositories: An
Automation Frontier


 


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Presentation 1/07:  

Pfizer-REMP Biofluid BioBank Store
(also available as PDF)

John Williams, Ph.D.;
Director

Pfizer Global Research & Development



The need, capacity and design of a unique -20˚C/-80˚C combined automated REMP
store for biofluid samples will be presented. The refrigeration design is novel
and based on a system developed by Pfizer together with Environmental
Specialties Inc. (ESI) for centralized -80˚C long-term freezers. REMP has
designed unique door access and robot access from a -20˚C compartment into the
-80˚C freezers. A constraint of +/-5˚C was imposed on all -80˚C operations. The
practical impact of this constraint on operational processes will be discussed.
Several aspects of the most critical component, the Luwa Environmental
Specialties (ESI) cascade freezer systems will be recounted with emphasis on
redundancy specifications. Performance data for the operational systems will be
discussed to illustrate the time constraints required to remain within the +/-
5˚C specification. This aspect has required new REMP software incorporating a
novel algorithm for optimal access to the multiple freezers to fulfill a single
order across multiple storage racks. Furthermore a specific loading algorithm
has been added to ensure all samples are loaded from the bottom of freezers to
maximize sample cooling in partial freezers.

DNA samples are stored in the -20˚C compartment that is a standard REMP
store. DNA samples are thawed and refrozen after each access and are in the
proprietary REMP 96-well 900ul tubes. Individual samples are replaced in their
original locations to prevent store fragmentation. In contrast biofluid samples
are in the same tubes but heat-sealed and used as single use samples to minimize
freeze/thaw cycles.

The timelines for design, manufacture, and installation, will be presented. A
number of functionalities that were developed for the earlier REMP stores and
their reuse will be discussed, together with the rationale for a partial FAT at
Oberdiessbach will be presented with respect to reduced time and cost versus
potential issues.



Presented at LRIG Mid Atlantic,
Biorepositories: An Automation Frontier

 


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Presentation 1/07:  
Rutgers
University Cell and DNA Repository
(also available as PDF)

Dr. David Toke;
Associate Managing Director

Rutgers University Cell & DNA Repository (RUCDR)



Dr. Toke will share his professional
expertise on:



 * managing large volumes of specimens and data generated from
research,

 * enabling public and private organizations to share data to
enhance the research process

 * addressing the short and long term storage and logistics needs of
biorepositories

 * meeting HIPAA and IRB compliance requirements and patient consent
restrictions 



Rutgers University Cell and DNA Repository is a nationally renowned
facility and has combined partnerships with the National Institutes
of Health (NIH), including the National Institute of Diabetes,
Digestive, and Kidney Disease(NIDDKD), the National Institute of
Mental Health (NIMH), the National Institute on Drug Abuse (NIDA),
as well as, private organizations, such as the Cure Autism
Now/Autism Genetic Resource Exchange.




Presented at LRIG Mid Atlantic,
Biorepositories: An
Automation Frontier


 

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Presentation 10/06:  


High throughput label-free detection of phosphor-specific
protein-protein interactions with the Epic™ system


Meng Wu, Ph.D.

Department of Neuroscience and High Throughput Biology Center (ChemCore)

Johns Hopkins University,
School of Medicine

 

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Presentation 10/06:  
Membrane Potential
Assay for identifying Sodium Channel Modulators


Shephali Trivedi

AstraZenaca


 

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Presentation 10/06:  
Ultra High
throughput screening for antagonists of a Gi-coupled receptor in a 2.2
ul 3456-well plate format cAMP assay


Michael Weber

Merck

 

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Presentation 03/06:  
The US Patent System and the Employed Inventor

Bart Zoltan

Wyeth Research, Pearl River, NY




A brief discussion of the American patent system, its rules and foibles, recent
changes, and proposed changes. Description of patent rights, inventorship, and
the corporate and personal advantages of patenting. Discussion of "patent
trolls", "submarine" patents and the role of the courts in the patent litigation
explosion.

Bart J. Zoltan is a Principal Research Engineer with Wyeth Research in Pearl
River, NY. He is registered to practice before the US Patent and Trademark
Office, holds nineteen US patents and was the New Jersey Inventor of the Year in
1990.

 

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Presentation 03/06:  
Recent Research in Microfluidics (PDF file requires Adobe Reader)

Prof. Robert Austin, Princeton University

 

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Presentation 02/06:  
Samples in DMSO: What an end user needs to know
(PDF file requires Adobe Reader)


Christopher Lipinski, Ph.D.; Adjunct Senior Research Fellow

Pfizer Global Research and Development, Pfizer, Inc., retired

The end user of samples in DMSO is someone who uses and stores samples for a
relatively short period of time. The body of existing literature suggests
storing samples in dry DMSO at room temperature for no more than three months
and then discarding them. DMSO and water exhibit very non-ideal behavior when
mixed together. This behavior is responsible for a range of property changes
when the two solvents interact. These include; the hygroscopicity of DMSO; the
viscosity increase when DMSO is wet and most importantly for this discussion:
the marked solubility decrease of compounds in wet DMSO. When compounds
precipitate from wet DMSO about half the time they can be resolubilized by
sonication. The trend in chemistry to make amorphous compounds is an advantage
in that initial solubilization in DMSO is easy. The downside is that the DMSO
solutions have to be kept absolutely dry and freeze thaw cycles need to be
minimized. Trifluoroacetic (TFA) contamination of samples in DMSO is a serious
problem. TFA as low as 10 nM is cytotoxic in 24-hour cell cultures. This is not
much of a problem in the typical short incubation HTS but it could be a problem
as longer time interval safety assays get pushed into discovery. When TFA
contaminated samples in DMSO become wet, acid hydrolysis becomes a serious
concern. Many heterocycles made by a dehydration step are perfectly stable under
neutral conditions but are hydrolyzed by TFA in wet DMSO.

 


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Presentation 02/06:  
Poor Aqueous Solubility and Compound Aggregation: Detection, Differences, and
impact on In-Vitro Screens
(PDF file requires Adobe Reader)

Joseph Goodwin

BD Biosciences




Poor aqueous solubility and compound aggregation are two persistent problems
that interfere with both high throughput and secondary screens. Poor solubility
and compound aggregation both directly impact the effective compound
concentration and the accuracy of the in-vitro assay results. In addition, the
formation of compound aggregates can cause false positives by interacting
non-specifically with the enzyme ligand interaction. The negative effects that
particle formation has on in-vitro screens will be discussed. In addition, new
methods that can be used to distinguish aggregation from precipitation will be
presented using the BD GentestTM Solubility
Scanner, a flow cytometry instrument specifically optimized for rapid and highly
sensitive detection of insoluble and aggregate particles. The primary
distinction of this technology verses other light scatter methods, is the
ability to generate distinct light scatter signals for each particle as it
passes through the excitation beam. This unique capability enables the analysis
of a wide variety of sample types (from traditional assay buffers to more
complex samples containing excipients and serum).

 

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Presentation 02/06:  
Automation of compound management at Schering-Plough Research Institute (SPRI)

Marybeth Burton; Associate Director, Chemical Technologies

Schering-Plough Research Institute

Proprietary research sample collections are one of the most valuable assets
for large pharmaceuticals companies. Investment in technology to store,
retrieve, prepare, and analyze this key resource is critical for the support of
current and future drug discovery screening efforts. This presentation describes
the project undertaken by Schering-Plough Research Institute (SPRI) to automate
compound management processes and highlights improvements in request processing
cycle time resulting from this initiative.

 


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Presentation 02/06:  

Practical Considerations for Enlightened Compound Management
(PDF file requires Adobe Reader)

Rhett Affleck, Ph.D.; V.P. Technology

Nexus Biosystems

Beyond the choices of storage systems, container types, and compound
selection, many questions remain regarding how to best achieve a compound
management facility’s goal: delivering the proper amount of each requested
compound – at the required throughput and at a reasonable cost. Precipitation
and degradation of compounds in DMSO stocks is a known problem. Should compounds
be stored dry, in DMSO, or both? If in DMSO, at what concentration? Should
multiple copies of each compound be aliquotted and stored? These and other
decisions will ultimately influence screening results and should be considered
by compound managers and screeners before processes are put in place that
needlessly waste or don’t actually deliver a large fraction of the library.

 


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Presentation 02/06:  
Compound Management, One Size Fits All? and Other Pitfalls
(PDF file requires Adobe Reader)

Paul Gosnell; Group Leader, Compound Management

Bristol-Myers Squibb




The past ten years of compound management has been an extremely dynamic period
of development and growth. During this period all of the major pharmaceutical
companies and many of the larger biotechnology companies have invested heavily
in their compound management capabilities. Much success has been achieved and
through a partnering with technology vendors, compound management has become an
inherent part of successful drug discovery. However, the past ten years has been
a time of rapid change and a myriad of paths have been pursued in drug
discovery, as a result many of the compound management solutions delivered have
been the victims of planning, design and implementation pitfalls. This
presentation will expose several common pitfalls of compound management and
discuss options for avoiding the same pitfalls in future compound management
endeavors.

 

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Presentation 02/06:  
GenVault: Dry-state DNA storage: Enabling Pharmacogenomics through Smart
Biosample Management
(PDF file requires Adobe Reader)

Dr. David Wellis, PhD; Senior Vice President Sales and Marketing

GenVault

The management of biosamples has become increasingly important for
pharmaceutical companies and contract research organizations in light of access,
traceability and cost requirements. Biosamples must be easily shipped,
repeatedly accessed and conveniently distributed. Biosamples must also be stored
in cost-effective, long term storage conditions that are secure and traceable.
GenVault exceeds these demands with a fully integrated sample management system
designed for optimizing storage and retrieval and quick accessibility of
collected biological samples. The core of the platform, the GenPlate, enables
long-term storage, high throughput access, standard shipment and recovery of
high quality DNA all at room temperature. GenVault’s state of the art system is
automated and offers clinical informatics to meet the needs of both small and
large repositories.

 


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Presentation 09/05:  


Electrophoretic Mobility Shift as a Detection Method for Inhibitors to
Protein Kinases
(PDF file requires Adobe Reader)


Jonathan Lippy;

Bristol-Myers Squibb Lead Evaluation Department, Hopewell, NJ




An electrophoretic mobility shift assay was developed to identify
inhibitors of tyrosine and serine/threonine protein kinases. This
method utilizes microfluidics and electrophoretic separation to
directly measure the phosphorylation of a fluorescent peptide
substrate. Kinetic parameters and compound IC50 values were
determined and compared with results obtained by a standard
trichloroacetic acid (TCA) filtration assay. Initial reaction
velocities were used to determine kinetic constants (Km, Ki)
as well as compound mechanism of action. Reproducibility, sensitivity
and dynamic range of the electrophoretic mobility shift assay are also
discussed. The results from the study demonstrate electrophoretic
mobility as a robust, homogeneous, and non-radioactive method for the
detection of inhibitors to protein kinases.

 

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Presentation 09/05:  


When Robots Are Good…Fully Automated Thermo/CRS Robotic Assay System
with Dual FLIPR-Tetra and TAP SelecT Robotic Tissue Culture System

(PDF file requires Adobe Reader)


Veronica Soloveva, James LaRocque, Edward McKillip

Wyeth, Collegeville, PA




GPCRs and ion channels are very popular targets in research for new
drug candidates. Measurement of rapid biological responses in cells
using fluorescent dyes requires fluorescent plate readers equipped
with liquid handling automation. The FLIPR (Molecular devices Co) has
become one of the most popular and useful kinetic readers, because it
enables both simultaneous addition of liquid and simultaneous
monitoring for changes in fluorescence in every well of a plate. The
new generation FLIPR TETRA offers improved quality and reliability.
The fully automated Thermo/CRS robotic system integrates several
different automated elements such as a BioTek ELX washer unit, a PE
Evolution pipettor and PE FlexDrop dispensers that can perform
complex, multi-step processes, unattended. The sophisticated
Thermo/CRS robotic control software, POLARA, ensures that each and
every plate of sensitive cells in a large batch experiences the same
procedure as an individual plate assayed in the gentle hands of a
scientist. Such robotic systems can process hundreds of plates a day
and require large-scale automated support for cell preparation. The
TAP SelecT is an automated robotic system that can plate 100-300
plates of cells per day with inhuman accuracy and precision. In
addition to plating cells the SelecT can also pass and expand cell
lines. We will present a case study of a GPCR mediated Ca-flux assay,
where the exceptional quality of the continuously cultured cells
provided by the TAP SelecT was an enabling factor in reducing this
screen to practice.

Working together, this robotic team can enable high throughput
logistics for even very sensitive cell based assays.

 

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Presentation 09/05:  


Streamlining Assay Development: Lessons in Process Optimization
Through Protein Optimization
(PDF file requires Adobe
Reader)

James K. Kranz, Tara M. Mezzasalma, Jennifer L. Kirkpatrick &
Matthew J. Todd.

Johnson & Johnson Pharmaceutical Research and Development, L.L.C.
Exton, PA, USA




The successful automation of biological assays has shifted the
bottleneck of early discovery away from HTS. Two other potential
rate-determining steps within a project pipeline are those of
developing assays and determining compound mechanism of action. At the
Johnson & Johnson – Spring House RED unit, a frequently used screening
technology is ThermoFluor©, an in-house developed biophysical assay
where ligand binding is detected from small changes in protein
stability. Because many targets are analyzed using the same assay, the
assay development process has evolved into a straightforward series of
experiments designed to detect potential assay liabilities and/or
target nuances that could affect HTS results. This standardized
approach to assay development encompasses analyzing numerous
solutions, excipients, and relevant biochemicals, resulting in a
thorough picture of protein stability over a wide range of conditions.
Understanding these effects not only provides insights into HTS
screening results, but also in optimizing conditions for protein
purification and into relevant counterscreens for screening positives
in order to determine mode-of-action. Examples will be presented
demonstrating how ThermoFluor stability profiling has contributed to
prevent both of these other steps from becoming rate-determining. This
philosophy of profiling assays over a wide range of conditions has
been extended to enzymatic rate-based and endpoint-assays,
streamlining assay development for many systems.

 

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Presentation 01/05:  
Leveraging Compound Management Capabilities in Support of Drug Discovery:
From Sample Archive to Sample Distribution – Driving Efficiency and Improving
Productivity
(PDF
file requires Adobe Reader)

Michael J. Sofia,
Ph.D.
; Group Director New Leads Chemistry

Bristol-Myers Squibb Pharmaceutical Research Institute; Wallingford, CT




The physical compounds within a pharmaceutical company’s compound collection are
the embodiment of many years of creativity and innovation, and through the
screening process, these compound assets are the genesis of new leads and future
drugs. Therefore, for the future success of the business, it is essential that
these assets be effectively managed and leveraged to support all drug discovery
needs from lead discovery through lead optimization. Pharmaceutical compound
management organizations have evolved to manage these critical compound assets
and to service the vast array of compound needs for global discovery operations.
Technology advances and process optimization have broadened the scope of
compound management’s impact on the drug discovery environment and have lead to
significant productivity and efficiency gains. The expanded role of compound
management within the BMS drug discovery environment and the impact of
technology and process development on functional and organizational productivity
and efficiency will be described.

 

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Presentation 01/05:  
Impact of Acoustic Non-Contact Transfer of Compounds upon Compound Management
and Ultra High Throughput Screening


Timothy Spicer;
Research Scientist

Bristol-Myers Squibb Company; Wallingford, CT



Research and development organizations are under constant pressure to
streamline processes, remove bottlenecks and reduce costs in order to
be successful in new drug development. The demand to move from
384-well based screening to rapid and miniaturized screening in
1536-well density formats, from a pharmaceutical development
perspective, has been a priority for many years and until recently,
largely unsatisfied. Recently, we have overcome a significant hurdle
towards that goal by implementing acoustic non contact droplet
ejection (ADE) to enable the reformatting of compounds from 384-well
source plates into 1536-well assay plates. This has been coupled to
fully automated flexible screening platforms to allow us to screen
100K compounds per day. While we have realized the power of this new
technology in terms of enabling ultra high throughput screening, there
are multiple changes that must be properly understood and implemented
within our current compound collection supply line. However, the
benefit with regards to reagent costs, consumables costs, the
environment, the potential for closed loop screening, the potential
for compound conservation and the ability to acoustically audit each
source well justify these changes and will be discussed.

 

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Presentation 01/05:  
Fully Automated Compound Distribution Center

Collette DeChard;
Manager Basic Biological Support; Compound Management Group

Merck & Co. Inc.; Rahway, NJ




Four years ago Merck’s Compound Management Group started a journey to design,
develop and implement a Fully Automated Compound Distribution Center. Come see
how our vision became a reality!

 

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Presentation 01/05:
  


Compound precipitation from DMSO and the synergy between water
uptake and freeze / thaw cycles




Christopher Lipinski, Ph.D.
; Adjunct Senior Research Fellow

Pfizer Global Research and Development, Pfizer, Inc., retired




Freeze / thaw cycles have been recognized as deleterious to
compound storage in DMSO stock solutions but largely for the wrong
reasons. Historically, freeze thaw cycles have been viewed mostly
as harmful with respect to compound stability, i.e. chemical
degradation. This is probably incorrect. Freeze / thaw cycles in
synergy with water uptake into DMSO are primarily harmful with
respect to compound precipitation. The synergy aspect is very
important. It may be difficult to experimentally show an adverse
effect of freeze thaw cycles if the DMSO is bone dry or if
materials initially dissolved in DMSO are crystalline as opposed
to amorphous. It is the uncontrolled water uptake into DMSO stocks
in synergy with cooling that is the problem and that is solved by
single freeze thaw tube storage systems. The bottom line is to
treat DMSO in compound storage as if it were a water sensitive
reagent.

Can anything be done about precipitated samples? Rather
remarkably the answer is yes. In the majority of cases
precipitated samples can be re-dissolved by sonication. This
behavior is beneficially unexpected, is without literature
precedent and is counter to simplistic thermodynamic
considerations. In a minority of cases sonication induces
precipitation from super saturated solutions. This behavior does
have limited literature precedent.

 


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Presentation
10/04:
 
United Devices – The Grid Driven Enterprise
(PDF file requires Adobe Reader)

Ed Hubbard , President and Founder

United
Devices




During this interactive session, President and Founder Ed Hubbard will outline
United Devices’ vision of the Grid Driven Enterprise. Through industry examples
from leading pharma companies around the world to the work United Devices has
completed on its public grid, you will learn about the power and impact of Grid
computing, how it is changing the drug discovery process, and how it is
reshaping clinical research.

 

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Poster
at 2004
NCI-Frederick/Ft. Detrick Spring Research Festival, May 12-13, 2004,
Ft. Detrick, Maryland
: 
Overcoming the
Problems Associated with Long-Term Storage of Compounds in DMSO

(PDF file requires Adobe Reader)
  
[Note: Link to

Recommendations.doc
]


Timothy J. Waybright and Thomas
G. McCloud


Natural Products Support Group, SAIC-Frederick, Inc.

National Cancer Institute at Frederick, Frederick, MD

 

bullet
Presentation 02/04: 


Lessons Learned in Liquid Dispensers Validation


Jonathan Peterson, PhD.

Instrument Validation Manager

Molecular Devices Corp.

Getting a liquid handler “dialed in” for precise, reliable
operation can consume many hours (and many cases of microplates).
Having been through this discovery process on a number of instruments,
Molecular Devices has developed some expertise in validating its
liquid handlers. We will present some of the lessons we’ve learned
during the development and validation of fluidics instrumentation.
Some topics covered in this presentation will include: How do you
select an appropriate detection method (absorbance vs fluorescence)?
How do you select an appropriate dye and concentration? What can you
do to minimize detection artifacts? What can you do to minimize
meniscus effects? Special considerations for air displacement
dispensers. How to characterize carryover and tip washing
effectiveness.

Note: John has published a related paper. The
citation info is: Petersen J., Nguyen, J. Comparison of Absorbance and
Fluorescence Methods for Determining Liquid Dispensing Precison. JALA
(2005) Vol. 10, No. 2, pp. 82-87.

 


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Presentation 02/04: 
Stability of
Compounds Stored in TekCel Plate Management System: Application of New
Approaches for Ultra-High-Throughput Analysis of Compound Stability


James A. Connelly Ph.D.

Director of Library Production and QC

Aventis Combinatorial Technologies Center

Tucson, Arizona


 


bullet
Presentation
01/04:
 


Biological and Environmental Repositories –
Current and Future Directions


Robert Hanner, Ph.D., President

International
Society for Biological and Environmental Repositories (ISBER)




Repository based specimen collections are an essential part of the
infrastructure underpinning life sciences and biotechnology. They can contain
environmental samples, culturable organisms (e.g. micro-organisms, plant, animal
and human cells), replicable parts of these (e.g. genomes, plasmids, viruses,
cDNAs), viable but not yet culturable organisms, tissues and organs, as well as
databases containing geographical, molecular, physiological and structural
information relevant to these collections. Such repositories contain valuable
(often irreplaceable) samples that might have been collected for one purpose,
but because of the unique population they represent, might be useful to many
future investigators for many other purposes. The International Society for
Biological and Environmental Repositories (www.ISBER.org) serves as a forum to
share knowledge and experience among repositories, so that collectively, they
can operate more efficiently to build and maintain collections while giving
consideration to emerging new technologies. Because repositories tend to expand
with time and the emergence of new research techniques, a pressing need exists
to facilitate the automation of many repository activities, which involve both
specimens and associated data. To illustrate this phenomenon several new
initiatives are discussed, including the National Dialogue on Cancer, the
National Childrens Study, and DNA barcoding.

 

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Presentation 01/04: 
Septa Applications for Compound Preparation



Sam Abdelhamid and Paul Blake

Purdue Pharma, Cranbury, NJ, USA

Controlling the amount of water in chemical samples has become a priority
among compound preparation departments. It is well known that DMSO can quickly
absorb water from the surrounding air. This can compromise screening samples by
lowering the concentration of dissolved material, and or causing sample
precipitation. The introduction of septa based applications cannot only save
time, by eliminating de-capping steps; they can also reduce the amount of water
absorbed by solvents. By using vented tips that are filled with nitrogen, it is
now possible to aspirate and dispense solutions from vials and deep well plates,
without allowing the sample to come in contact with air. The use of liquid
handling systems that incorporate septa and vented tips can also be used for
combinatorial chemistry methods that use water sensitive reactants (i.e. acid
chlorides). Septa caps ensure that moisture does not come into contact with air
sensitive reagents. Various customs racks, holders, and vented tips were
integrated with our current liquid handling procedures to yield liquid transfers
under an inert atmosphere. The equipment and supplies used to implement these
procedures, along with results, will be discussed in detail.

 


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Presentation
01/04:
 
Integration of Sample
Management & HTS at Wyeth



Michael Longden, M.S.,
Supervisor of Screening Resources Group, Screening Sciences
;
John Morin, Ph.D., Director HTS, Screening Sciences; Dominick Mobilio,
Ph.D., Director of Cheminformatics and Compound Resources, Screening Sciences

Wyeth Research, Pearl River, NY, USA




Two years ago, Wyeth Research presented at MipTec 2001 their plans for a hybrid
sample storage and retrieval system composed of modular units provided by 2
different vendors. (TekCel and The Technology Partnership) Although the price of
innovation included some unplanned but not unexpected delays, this system is now
complete. The installation will be described in detail, including the metrics of
operation. The chemical integrity and quantitative recovery of compounds from
this system will also be evaluated. The workflow enabled by this system and the
IT infrastructure that supports it have bridged the gap between compounds and
HTS at Wyeth.

 

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Presentation 01/04:  Compound Solubility
and HTS Screening


Christopher Lipinski, Ph.D., Adjunct Senior Research Fellow

Pfizer Global Research and Development, Pfizer, Inc., retired

Sessions on reproducibility in HTS screening appear in the 2003 and 2004
annual meetings of the Society for Biomolecular Screening. The focus has largely
been on the biological aspect, i.e. how large is the overlap in screening
results when the same library of compounds is tested against the same target but
using different assay methods. What is only slowly being realized is that there
is another dimension to the HTS screening quality issue. HTS assay quality is
very much better if you really know the concentration of compound in DMSO stocks
and if you really know the compound concentration when the DMSO stocks are
diluted into aqueous assay medium. Relevant to this issue are the following
sub-topics: 1) from the 1880’s Oswalds “rules of stages” and why it explains
many DMSO solubility issues; 2) the dependence of DMSO freezing point on water
content; 3) what exactly is there about freeze thaw cycles that causes
solubility problems; 4) why is there such erratic behavior in terms of
precipitation from DMSO and 5) what is the evidence that globally about 20% of
compounds might ultimately have a DMSO solubility problem. Additionally, what
has changed in the last year in terms of software and hardware that could help
with the compound in DMSO solubility problem will be discussed.

 


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Poster 11/03:
Drug-Likeness and
Lead-Likeness: An Overview of Recent Studies


Zhengming (Jimmy) Chen, Purdue Pharma L.P., Cranbury, NJ

The distinction between drug-like and non drug-like molecules has been a hot
research topic in recent years. The most well known early study in this field is
the “Lipinski’s rule of five” which was derived empirically from the analysis of
the World Drug Index on the properties that maximize an oral drug candidate’s
probability of surviving clinical development: molecular weight (MW) < 500,
number of hydrogen bond donors < 5, number of hydrogen bond acceptors < 10, and
ClogP < 5. The rule of five is now widely used to filter out compounds likely to
have poor pharmacokinetic properties early on in drug discovery. Lead-likeness
(compounds’ likelihood to be good lead candidates), as distinct from
drug-likeness, is a new concept that is gaining acceptance in recent years.
Lead-like molecules are generally smaller to allow for structural additions to
enhance effectiveness during lead optimization, and is being incorporated into
the library design and lead optimization processes. In this presentation, I am
going to present an overview of recent studies on the topic of drug-likeness and
lead-likeness. The presentation will provide a few intriguing insights into the
influence of molecular properties on the likelihood of progression through the
drug development process and trends in modern drug discovery.


bullet
Poster 11/03:
SHOW, Sample Handling Operation
Wizard


Ping Du, Livingston, NJ

 

Sample Handling Operation Wizard (SHOW) is a system developed to
guide manual sample handling in the research laboratory. It comprises a
sample tray mounted on a flat-panel computer monitor. Up to four
transparent micro titer plates and up to 8 reagent vials may be placed
on the sample tray. Images of the wells of the plates and vials are
generated on the monitor and controlled by computer software. These
images are directly aligned with the positions of the physical wells. By
highlighting the wells or vials involved in a sample handling step of a
pre-defined protocol, manual operation can be performed with precise
guidance from the system. As a result, the risk of locating a wrong
sample or placing a sample at a wrong location can be minimized, and
sample handling operations become more efficient and less stressful.


bullet
Presentation
11/03:
 

Automation in
Pharmaceutical Profiling


Edward H. Kerns, Li Di, Susan Petusky, Susan Li and Donna
Huryn Wyeth Research, Chemical and Screening Sciences, Princeton, NJ

 

Selection and optimization of candidates for activity and selectivity
have traditionally played a dominant role in drug discovery. However, in
recent years the complimentary nature of pharmaceutical properties in
candidate success has been recognized. This has led to the
implementation of pharmaceutical profiling as part of the discovery
process. Several objectives of drug discovery pharmaceutical profiling
can be met through strategies and tactics that involve automation: 1)
The need for more information on in vivo delivery of the candidate to
the therapeutic target has led to the implementation of assays that
model key in vivo ADME barriers; 2) The need to improve discovery
efficiency has led to accelerated analysis and early collection of data
to avert ADMET problems that cause failure at later stages; 3) The need
to perform discovery research more effectively has led to the
application of pharmaceutical property information to better plan and
interpret discovery activity assays. These applications require high
capacity because of the large number of discovery compounds and speed
because discovery moves quickly. This presentation describes the
automation of pharmaceutical profiling assays for the properties:
integrity, lipophilicity, solubility, permeability, metabolic stability,
and CYP450 inhibition. The management of the resulting data and its
delivery to discovery teams are also key elements of the pharmaceutical
profiling workflow.


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Presentation
09/03:
  The Way of XML — Saving time and increasing
reliability with XML


Liam Quin, W3C XML Activity Lead,
liam@w3.org,

http://www.w3.org/People/Quin/




The Extensible Markup Language (XML) has seen widespread use in
industry, in government, in research, and seems still to be spreading.
Its popularity lies partly in the fact that it’s a relatively simple and
open specification, freely downloadable; partly in the fact that it is
an intuitive way to represent structured information; and partly in the
fact that every new XML document and every new XML tool multiplies the
usefulness of every other XML document and tool, through
interoperability.




Liam Quin is XML Activity Lead at the World Wide Web Consortium, the
organization that publishes and maintains the XML Specification. He will
give a brief philosophical background to XML, show some ways in which
use of XML can give unexpected benefits, and give an overview into how
some XML specifications fit together.


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Presentation
09/03:
 
Application of the Sotax AT70smart within a development
laboratory


Dónal J Murphy, Ph.D.; Analytical Development; AstraZeneca UK



In the pharmaceutical industry, Good Manufacturing Practice (GMP) guidelines
require careful validation of automated processes so that fitness for purpose
can be demonstrated. This is also true of automated dissolution where validation
must be performed for each of the products to be tested to ensure reproducible
and robust method operation. Key validation considerations are discussed
including some which are specific to the Sotax AT70smart. Experiences with the
Sotax AT70smart and its application within a development laboratory are also
discussed.


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Presentation
01/03:
  Quality
Perspectives for Compound Storage


Dania Yaskanin, Ph.D.; Manager, Johnson and Johnson Pharmaceutical Research and
Development Corporate Compound Logistics Center


The Corporate Compound Logistics Center (CCLC) is actively investigating
compound quality and storage issues. Several approaches are being used,
including studies of production materials, process verifications, and storage
environment.

Production material changes over the past year have included compound storage
vials, microplate seals, and DMSO vendors. The compound vials were replaced with
a different vial type to improve compound handling and data quality. At J&J PRD,
solubilized compounds in DMSO are stored in microplates in a controlled
environment. To optimize compound storage in this environment, seven different
microplate seals were evaluated for seal integrity with physical stress tests
and detection of materials leached into DMSO. A portion of the solubilized
compound inventory is also being moved into sealed polypropylene tubes that will
allow comparison of compound quality when stored in plates versus tubes.

Process verifications have shown that solvent handling during compound
solubilization and dilution influences the quality of compounds in solution.
Qualitative analysis of a representative portion of the compound library is
underway, with the goal of repeating the analysis over several years to record
compound deterioration over time. Additional procedures for evaluating compound
quality are currently being added to department capabilities, such as
quantitative analysis of compound concentration, percentage of water content,
and detection of contaminating materials extracted by DMSO. 


bullet

Presentation
11/02:
A
Summary of Compound Stability Experiments Performed at GlaxoSmithKline


Zoe Heaton, GlaxoSmithKline


bullet

Presentation 11/02:

Ensuring Compound Integrity With Modular, Scalable, Automated Solutions


Stuart Naylor, European Sales Manager, TekCel Inc.


bullet

Presentation 11/02:
Synthesis and Screening
in Micro Reactors


Paul Watts, University of Hull, UK


bullet

Presentation 11/02:


Managing the ‘Crown Jewels’


Krystyna Holden, Millennium Pharmaceuticals


bullet

Presentation 11/02:


Purification for Quality


Biotage, Inc.


bullet

Presentation 11/02:
Automation
Without Robotics, a Comparison of Common Approaches to Low Temperature
Compound Storage


Ian Whitehall, TTP LabTech


bullet

Presentation 11/02:
Introduction of the
Personal Digital Assistant into the Analytical Laboratory


Dan Brooke, GlaxoSmithKline


bullet

Presentation 11/02:  Evaluation of
Technologies for Potassium Channel Targets Compound Screening


Dr. Weimin Tang, Principal Scientist, Johnson and Johnson/Pharmaceutical
Research Institute

We have seen a surge of research in development of fast and reliable HTS
methods for ion channel targets. This is driven by the fact that hundreds of ion
channel genes from the human genome project and their functional association
with human diseases. Some of the channels have been proved to be important in
the drug discovery process such as HERG and various calcium channels.
Traditional potassium channel functional study has relied on Patch-Clamp
electrophysiology and Rb86 efflux assay. However, those methods were not easily
deployed for drug screening because of the concern for cost and speed.
Pharmaceutical companies have relied on dye based ion channel readers such as
FLIPR and VIPR for many years and the results are controversial. This talk will
focus on the development of non-radioactive Rb+ efflux assay using ICR8000, a
system designed for medium throughput functional HERG channel screening. The
development of HTS ICR12000 will also be discussed.

 


bullet
Presentation 11/02:  Transfluor™
Technology: Universal, High-Throughput Imaging Assay for G Protein-Coupled
Receptors


Christine Hudson, Senior Scientist, Norak Biosciences, Inc




Norak Biosciences, Inc. is using its proprietary Transfluor™
technology as a universal, cell-based, imaging assay for known and orphan GPCRs.
The Transfluor™
technology is based on a physiological process common to nearly all GPCRs–receptor
desensitization. Specifically, the assay utilizes the redistribution of
fluorescently-labeled arrestins from the cytoplasm to receptors at the plasma
membrane to monitor the activation (or inactivation) of GPCRs. Transfluor™
is quantitated on multiple automated image analysis systems, achieving high
signal to background ratios (5:1 to 25:1) and screening rates of 50,000
compounds per day. The assay discriminates between agonists, partial agonists,
and antagonists while providing valuable pharmacological information on efficacy
and potency. In contrast to present methods of screening GPCRs, the power of the
Transfluor™
assay is in its simplicity, sensitivity, and applicability to all GPCRs without
requiring prior knowledge of natural ligands or how a given receptor is coupled
to downstream signaling pathways.


bullet

Presentation 11/02:

A Calcium Flux
Assay for Drug Screening In The LabChip System


Abbie L. Esterman,
Ph.D., Senior Applications Scientist, Caliper Technologies




A high throughput calcium flux assay was developed for the LabChip™
microfluidic system. The system accesses samples from a microplate,
mixes the samples with cells flowing through a microchannel and reads
out cellular responses using fluorescence detection. Calcium responses
resulting from G-protein coupled receptor activation were measured. The
ability to conduct screens for GPCR agonists and antagonists was
demonstrated by screening for agonists and antagonists of the
m1-muscarinic receptor mediated calcium response in CHO cells. The
LabChip™ system uses as few as 50-100 cells per sample and less than 10
nl of sample and 10 nl of agonist per measurement. Because of the low
cellular and reagent consumption, and high data quality obtained with
the microfluidic device, the LabChip™ system should be widely applicable
in high throughput screening.


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Presentation 11/02:
Count the Ways:
Automated Biochemical Counter-Screening for Kinase Drug Discovery



Gordon Alton, Department
of Biochemistry, Pfizer Global R and D, La Jolla Labs



One of the most critical issues for protein kinase drug discovery is
selectivity. Since most kinase inhibitors are targeted to the ATP-binding
site and there are more than 500 kinases in the Human genome off-target
inhibition is a significant problem. As the potency of lead compounds
increase through iterative cycles of medicinal chemistry and structure
based drug design it is important to identify off-target inhibition. To
facilitate counter-screening by individual project biochemists routine
robust automation of dose response curve kinase assays are required. In
contrast to an HTS assay these automated assays are designed to provide
high precision data for a small number of compounds for multiple kinases.
This presentation will outline some of the robotic assay development
solutions that have been implemented in the Biochemistry Group at Pfizer
La Jolla.

View / Download as PPT file


bullet

Presentation 10/02:
The Human
Genome Project: A view from the trenches


Dr. Bruce A. Roe George, Lynn Cross Research Professor, Advanced Center
for Genome Technology, Department of Chemistry and Biochemistry,
University of Oklahoma


bullet

Presentation 9/02:
Issues in
Compound Storage in DMSO


Christopher A. Lipinski, Adjunct Senior Research Fellow, Pfizer Global
R&D, Groton Labs


bullet

Presentation 9/02:
Through-Hole
Microarrays: A High Throughput Platform for Synthesis, Storage and
Screening
(PDF file)

Tanya Kanigan, BioTrove Inc.


bullet

Presentation 9/02:
Multilayer Soft
Lithography MSL for Life Sciences


Rodney Turner, Fluidigm


bullet

Presentation 6/02:
Design of a Laboratory for Cell-based High Throughput Screening


Jessica Rivers, Research Associate, Maxim Pharmaceuticals [www.Maxim.Com]
San Diego, California


bullet

Presentation 5/02:
Low Volume Liquid
Handling By A Dispensing Well Plate™


Roland Zengerle, IMTEK Institute for Micro System Technology,
University of Freiburg, Germany,
http://www.imtek.de/anwendungen


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Poster (PDF):

High-Throughput Protein Crystallography with the Corning Protein
Crystallography Plate on the Beckman Coulter Multimek 96 Automated 96-
Channel Pipettor


Phillip Bradford, Dr. Rongbao Li, Jennifer Fiedler and Dr. Thomas
Fletcher III (Southern Research Institute), Edwin Dario and Tom Harrison
(Beckman Coulter), Dr. Ma Sha and Gerald Campbell, Jr. (Corning)


bullet

Poster (PDF):
An Automated Platform for Miniaturized Protein Crystallization

Holger Eickhoff, Patrick Umbach, Lajos Nyarsik , Martin Horn,
Thomas Przewieslik , Wolfram Saenger , Hans Lehrach , Günther Knebel ,
Peter Opfermann

The Protein Structure Factory, Free University of Berlin, Institute for
Crystallographie, Max-Planck-Institute for Molecular Genetics, Greiner
Bio-One GmbH


bullet

Poster (PDF) 1/02:
Minimizing Compound Exposure


W. Steven Fillers, Ph.D., TekCel, Inc., Hopkinton, MA


bullet

Poster (PDF) 1/02:
Automated Microplate Sealing and Unsealing with SealTite


W. Steven Fillers, Ph.D., TekCel, Inc., Hopkinton, MA


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Presentation 1/02:
Modular Strategies for
Automated Storage and Retrieval


John Morin, Ph.D.; Biological Chemistry Section, Wyeth-Ayerst Research, Pearl
River, NY, USA



The Wyeth-Ayerst Research (WAR) High Throughput Screening (HTS) group is
responsible for supporting project teams from 6 different therapeutic areas and
maintains HTS laboratories at 2 separate sites. In addition to providing assay
development and HTS services, we are responsible for dissolving compounds in
DMSO and formatting them into micro-titer plates for distribution inside and
outside the company. The WAR corporate library has swollen over the past 10
years through merger activities and the acquisition of combinatorial chemistry
collections. By mid-1999 we estimated that sample preparation, storage and
retrieval were consuming more than half of our personnel and equipment
resources, so we began a project to improve our sample management functions. We
achieved greater efficiency almost immediately simply by consolidating
responsibility for sample management to a small group of volunteer specialists.
Further gains came from collapsing our old 96-well sample plate library into
384-well plates, but the manual storage and retrieval of sample plates in over
70 upright freezers was still a bottleneck. We therefore circulated a Request
for Proposals to several leading vendors of automated storage and retrieval
systems. After many presentations and extensive deliberation, we ultimately
chose to avoid the standard approach of a large, complex, integrated system with
multiple overlapping and interdependent functions and to invest instead in a
novel hybrid system composed of modular units provided by 3 different vendors:
(TekCel, The Technology Partnership and Packard/CCS)  I will describe what we’re
building and why we chose this path. I will also update our progress as elements
of the system have begun to arrive.

View / download as
PDF file


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Presentation 1/02:  
SmartPlate integrates library management and assay platforms to increase
throughput and preserve compound library


Jeffrey A. Karg, PE;
Boston Innovation Inc.; Cambridge, MA



Assay miniaturization has pushed the limits of fluid handling. 384 and 1536
well screening requires accurate and reliable compound dispensing during the
reformatting procedure. This time-consuming and wasteful step is eliminated with
the SmartPlate shipping, storing, and dispensing technology that includes
integral dilution. A new concept assigns a DMSO dissolved compound to an
individually addressable sealed tap. The taps are the storage, metering,
dispensing, and diluting elements and formatted in a 384-well plate-based array.
Compound dispense volumes range from 5-200nl. Reformatting, disposable tips, and
wash cycles are eliminated. This presentation will highlight how SmartPlate10
works, implementation examples, and current performance data.

Download Zipped Powerpoint file


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Poster (PDF):
The
Effect Of Sealing Versus Lidding Plates On Degradation And Water Uptake Of
Compounds Held In DMSO At 4ºC


Zoe Heaton, César Ramírez-Molina – Analytical Sciences, Dr Sue Holland, Rob
Hughes, Dr Rob Lifely, Compound Management, Linda Robb, Statistical Sciences

GlaxoSmithKline, Stevenage, UK


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Poster (PDF):
The
Effect Of Freeze Thawing And Storage Time On Degradation Of Compounds At 4ºC
Under Humidity Control Using Experimental Design


Zoe Heaton, Analytical Sciences, Dr Sue Holland, Rob Hughes, Dr Rob Lifely,
Compound Management, Linda Robb, Statistical Sciences

GlaxoSmithKline, Stevenage, UK


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Poster (PDF):
The Importance Of Karl Fischer In Quality Control For The Support Of Automated
Liquid Stores


Zoe Heaton, Mark Connell, Analytical Sciences, Dr Sue Holland, Rob Hughes, Dr
Rob Lifely, Compound Management

GlaxoSmithKline, Stevenage, UK


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Poster (PDF):
The
Effect of Freeze/Thaw Cycles on the Stability of Compounds in DMSO


B. A. Kozikowski, L. E. Williams, D. Tirey, B. Kuzmak and K. L. Morand


Procter & Gamble Pharmaceuticals


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Poster (PDF):
High
Throughput Screening Degradation Study: Determination Of Storage Options And
Retention Limits


L.E. Williams, B.A. Kozikowski, T. Burt, B. Kuzmak, K. L. Morand
Williams, B.A. Kozikowski, T. Burt, B. Kuzmak, K. L. Morand


Procter & Gamble Pharmaceuticals


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Presentation 11/01:
DNA microarray
fabrication and processing – Automation in the laboratory


Gary Hardiman Ph.D., Director BIOGEM (BioMedical Genomics Microarray
Facility), Division of Biology, University of California, San Diego, CA


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Presentation 11/01:
An Automated
Approach to the Supply of Samples for Screening


Terry Wood, Pfizer Global Research & Development, Sandwich, UK


Download Powerpoint  file


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Presentation 11/01:

Liquid
handling in Chemical Synthesis- The Celltech approach


Nick Ray – Celltech R&D, Granta Park, Cambridge  UK

View / download as
PDF file


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Presentation 9/01:

A cost-effective way to
pipet 384 samples simultaneously


John Herich, Manager- HTS, Maxim Pharmaceuticals


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Poster (PDF):
How Exposed Are Your
Compounds?


W. Steven Fillers, Ph.D., Andrée Proulx and Marsha Paul, TekCel, Inc.,
Hopkinton, MA


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Presentation 6/01:
Compound
Management Automation at AstraZeneca


Ian Yates, Head, Compound Management & Automation, AstraZeneca HTS
Centre Sweden




The AstraZeneca HTS Centre based in Mölndal, Sweden is one in a
network of four HTS centres that support the AstraZeneca drug discovery
process. Integrated within the department is the Compound Management Team.
This team, in partnership with compound management groups across the
organisation, is responsible for managing the compound collection and
ensure it’s accessibility to both the local HTS group and scientists
globally.

In common with many other companies in the pharmaceutical industry
Astrazeneca has experienced a dramatic increase in both the size of it’s
compound collection and it’s screening capacity. This has resulted in
tremendous pressure being placed on compound management groups to manage
and supply more compounds, and to do so quicker.

This presentation will look at the automated systems that have been, are
currently being, and will be, used at the HTS Centre in Sweden to enable
us to meet this high demand. It will start with an overview of the systems
that were implemented when the Centre was founded five years ago. It will
then cover the systems in use today and conclude with a preview of a new
automated compound management facility planned for the Centre. This
facility forms part of AstraZeneca’s strategy for a more efficient and
truly global compound collection.


Download Powerpoint  file


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Presentation 6/01: 
Conversion of
manual access of 384 lidded plates to an automated storage and retrieval
system



Pavel Rychetsky,
Martha Ackerman, Patti Willson; Biology Automation

Selectide, a subsidiary of Aventis Pharmaceuticals Inc., Tucson, Arizona,
USA



Compound management and logistic support is an integral part of
high-throughput screening activities. Usually, intermediate microtiter plates
with diluted compounds have to be prepared in advance of a screening run. We
eliminated this step by implementing a procedure for compound transfer directly
from 384-well compound storage plates into assay plates during a screening run
using a pin tool. After the screening run the storage plates are stored in
freezers and reused later in the next screen. As loading and unloading compound
plates for routine HTS runs became the most time-consuming step in our lab
operation, we felt that further efficiency could be achieved by integrating an
automated storage and retrieval system by TekCel Corp. into the HTS robot. The
storage system is capable of presentation of storage plates to the screening
robot without human intervention. Two major areas of application for the
refrigerated storage and retrieval system are HTS and "cherry-picking". The
advantages of this storage system concept, with its unique plate sealing
capability, compactness, and expandability, will be presented.


Download Powerpoint  file


View / download as
PDF file


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Presentation 6/01: 
Mass Storage / Retrieval of Chemical and Biological Libraries


Dr. Terry V. Iorns, Iorns Consulting, Inc., 6334 E. Viewmont Drive, Mesa, AZ
85215 USA, E-Mail: tiorns@iorns.com ,
http://www.iorns.com




Storage, retrieval, and distribution of chemical and biological libraries is
a critical activity in drug discovery. Successful high throughput screening
requires careful coordination and interaction of screening technology with assay
/ reagent preparation and availability of screening libraries. Failure of any of
these to come together leads to a problem in the discovery program.

What is a library? Consider a library as a collection of chemical compounds or
biological substances that should be handled or screened together. Examples
include:

· Compound Collection – all the compounds/substances a pharmaceutical company
can put their hands on.

· Related compounds by activity in a class of assay – such as a kinase or
protease library.

· Related by structure or synthesis – combinatorial libraries

· Purchased collections

How are libraries received, stored and exchanged? There are four major ways to
handle libraries:

· Solubilized in plates

· Solubilized in tubes or microtubes

· Neat substances in vials

· Neat substances in tubes or plates

Neat substances are generally quite stable and are generally stored at room
temperature. Sometimes neat substances must be stored cold, in an inert
atmosphere, or protected from light. Solubilized substances are generally stored
in 100% DMSO. Most organizations store these solutions cold, near the freezing
point of DMSO. Source plates or tubes generally contain a fairly high
concentration, usually in the range of 3 to 20 mM. Collections are generally
distributed to screening laboratories at much lower concentrations, usually less
than 1 mM and often in the mM range.

Handling issues to consider:

· Automation of processes to prepare and distribute libraries

· Vendor and equipment reliability

· Sealing tubes and plates to protect solutions from evaporation or water
absorption

· Unsealing or piercing plate seals to allow sampling by screening robots

· Stability of substances in solution over long periods of time and conditions


This paper will conclude with a survey of equipment and techniques to make the
handling of libraries easier and more reliable. Products from several vendors in
the following categories will be mentioned:

· Storage and retrieval systems

· Sealing and piercing devices

· Replication systems

· Robotic systems



Download Powerpoint  file


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Poster 6/01: 
Comparison
of Microplate Sealing Tapes Using Standardized Test Protocols


Terry W. Lewis, PhD, Maurice H. Kuypers, Mialena M. Walker Medical
Specialties Department – 3M Health Care – St. Paul, Minnesota



Adhesive tapes have become an attractive option to cover microplates in
bioanalytical, genomic, and pharmaceutical research. Primary performance
criteria for microplate adhesive tape seals include: prevention of evaporation
from the individual wells; low contamination of well contents by the tape
adhesive; prevention of cross-contamination between individual wells, and clean
tape removal for access to well contents. Depending on the particular research
objective, other criteria for adhesive tape seals may be important. These
include pierce-ability for access to individual wells without entire tape
removal, good optical properties, for monitoring well contents through the tape,
and temperature resistance over wide ranges to include compound storage and PCR.
This poster will describe results of a wide variety of adhesive tape performance
testing designed to mimic actual industry use conditions. The tests include
evaporation data with water, DMSO, and aqueous mixtures of isopropanol,
methanol, and acetonitrile. Microplate composition and manufacturer were also
varied. Temperature conditions ranging from -70° C up to room temperature and
actual PCR cycling were evaluated. Other testing results on adhesive
extractables, tape optical properties, and tape application and removal will be
presented.


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Presentation 4/01: 
Micro-volume
liquid dispensing. Analysis and examples


Ilya Feygin, Manager Research
Engineering

Pharmacopeia, Inc



Precise dispensing of micro volumes of reagents in liquid form becomes more and
more important with continuing miniaturization of the High Throughput and High
Content Research process. Applicable to all platforms, from medium and high
density plates to "micro-chips", fast and repeatable liquid dispensing
can often become the key to a successful experiment.  Various methods of
existing dispensing technologies will be analyzed and Pharmacopiea’s experience
in implementing high speed dispensing will be presented. 

Download Zipped Powerpoint file


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Presentation 1/01: 
A Complete Solution for Drug
Discovery


Steve Fillers, Ph.D.;
Chief Scientific Officer


TekCel, Inc.

Download
Powerpoint  file



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Presentation 9/00: 
Comparison of Robot Arms for the Laboratory Environment


Douglas Gurevitch, P.E.,
Director of Microarray Automation

Biocept, Inc.


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Presentation 4/00: Trident Library Synthesizer
For Automation of Multistep Solution Phase Synthesis


Jeff Labadie, Argonaut Technologies, 887 Industrial Road, Suite G, San
Carlos, CA 94070


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Presentation 1/00: 
The TekCel TekBench:
An Innovative Tool for High Throughput Screening


Ben Knight

Millennium Pharmaceuticals

Download
Powerpoint  file


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Presentation 1/00: 


A Novel Process for
Completely Automating Microplate Sealing, Unsealing and Storage



Julian Warhurst;
Chief Technical Officer

TekCel Corporation, Hopkinton, MA 01748



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.



Download Powerpoint  file


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Presentation: 
Molecular
Braille: A Novel Technology for Identification and Characterization of Compounds that
Modulate Receptor Function


Dale J. Christensen, PhD., Senior Scientist

Novalon Pharmaceutical Corporation


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Poster 10/99:

Automated
Solubility Analysis of Small Quantities of Drug Substance


John Troisi, Research Assistant Automation

R.W. Johnson Pharmaceutical Research Institute, Raritan, NJ


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Presentation 10/99:
Harnessing
the Power of Computational Intelligence to Identify Leads in HTS


Susan I. Bassett, Ph.D., Executive Vice-President, Global Technology Operations

Bioreason, Inc.


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Presentation 10/99:
High-Throughput
Screening Applications of a Novel Scanning Laser Imaging Technology


Sheri Miraglia, Ph.D., Senior Scientist

PE Biosystems


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Presentation 5/99:
Automated
High Throughput Pharmacological System, HT-PS® 100


Ilya Okun, Ph.D. – Vice President of Cell Pharmacology

AXIOM Biotechnologies, Inc.


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Presentation 5/99:
Assay
Translation: Some guidelines for turning a manual laboratory process into an automated
laboratory process


Douglas Gurevitch

Axys Pharmaceuticals


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Presentation 4/99: 
Development
of Fluorescence Polarization and FRET Assays for Tyrosine and Serine/Threonine Kinases


Dr. Jinzi J. Wu

Novartis Institute for Biomedical Research

Summit, New Jersey

Download Powerpoint  file


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Presentation 3/99: 
96 to 384 – Challenges and Solutions


Seth P. Cohen Ph.D.

Associate Director, HTS

Millennium Pharmaceuticals, Inc.


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Presentation 3/99: 
Automation Architectures for HTS and Their Impact
on Productivity


Julian Warhurst;
Vice President, Research and Development

TekCel Corporation, Hopkinton, MA 01748

Download
Powerpoint  file


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Presentation 2/99: 
A
Web Based System for Data Management


Richard Kozack

Ares Advanced Technology


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Presentation 1/99: 
Strategies For The Successful Sourcing of Robotic
Systems


Bob Trinka

Robocon Inc.


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Presentation 12/98: 
HTS and Lead Optimization Using FLIPR


Joseph Gunnet, Ph.D.

Principal Scientist, Endocrine Therapeutics

The R.W. Johnson Pharmaceutical Research Institute, Rt. 202, Raritan, NJ 08869


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Presentation 12/98: 
Automation of the assay development phase of
drug discovery


Damien Dunnington (1), Anthony Lozada (1), Hsiu-Yu Tseng (1), Paul Taylor (2) and
Frances Stewart (2)

1. Hoechst Marion Roussel, Route 202-206, Bridgewater NJ 08807

2. SmithKline Beecham Pharmaceuticals, 709 Swedeland Road, King of Prussia PA 19406


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Presentation 12/98: 
Validation of Engineered
Cell-Based Screens for G Protein-Coupled Receptors


E. William Radany, Ph.D.

Business Manager, Stratagene

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