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Announce: Laboratory Robotics CombiChem / HTS Meeting

Andy Zaayenga andy.zaayenga at bigfoot.com
Mon Apr 19 11:00:12 EST 1999


The Laboratory Robotics Interest Group Mid Atlantic Chapter

April 1999 Meeting
Combinatorial Chemistry & High Throughput Screening

Date: 
Wednesday, April 21, 1999

Place: 
Hanover Marriott,1401 Rt 10 E, Whippany, NJ 07981, Phone: 973-538-8811, Fax:
973-538-0291

Itinerary: 
Presentations and Discussion - 3:00 to 4:30 pm
Social Period, Vendor Exhibits, Food, Refreshments & Poster Session -  4:30
to 6:30 pm
Presentations and Discussion -  6:30 to 9:00 pm

Pre-Registration: Requested, not required.  Registering will allow us to
more accurately gauge seating requirements and refreshment needs.  Indicate
names of attendees and company affiliation.
Email:  andy.zaayenga at lab-robotics.org
Phone: (732)302-1038
Fax:      (732)302-9080

Agenda:    The Social Period will feature vendor exhibits, food and
refreshments.  Members interested in presenting a poster are encouraged to
do so.  Open career positions at your company may be announced or posted.
There is no fee to attend the meeting.  Bring a business card to drop in the
registration fishbowl - it eases registration and qualifies you for the
rosewood pen set drawing. 
_______________________________________

Presentation:  A New Reaction Block as the Core of an Integrated System for
High Throughput Automated Organic Synthesis.
Harold N. Weller, Walter Ruediger, Wen-Jeng Li, and John A. Allen
Bristol-Myers Squibb Company, Pharmaceutical Research Institute, PO Box
4000, Princeton, New Jersey 08543

A new reaction block has been developed that forms the core of an integrated
system for automated high throughput organic synthesis. Unlike many reactors
previously described, this new block is capable of either solid- or
solution-phase parallel synthesis. In addition, it can also be used for the
cleavage step from split and pool synthesis using commercially available
MicroKan™ reactors. The block offers large enough reaction scale to be used
for lead optimization, yet delivers products into standard 96-well format
for efficient post synthesis processing. The reaction block is based on a
novel multiple valve mechanism with a single functional moving part, leading
to low cost and high reliability.

Maximum efficiency of this new reactor system is obtained from consolidated
post synthesis processing regardless of synthesis method. Post synthesis
processing is based on product collection into custom microtubes in 96-well
format. Purpose built workstations process microtubes for weighing and
selection for screening.

This talk will describe the evolution and design of this new reactor system,
along with its place in an efficient overall automated synthesis operation.
_______________________________________

Presentation:  ALPHAScreen a novel non-radioactive homogeneous assay
technology for uHTS
Changjin Wang, Ph.D., Director, ALPHAScreen Technology and Systems, Packard
Instrument Company

This presentation will describe a novel assay technology termed Amplified
Luminescent Proximity Homogeneous Assay, and its applications in drug
discovery uHTS. The assay relies on two proprietary latex Donor and Acceptor
beads (~200 nm) and generates highly amplified long life fluorescent signal
when the beads are brought into proximity upon a biological binding event.
The Donor bead contains a photosensitizer which converts ambient oxygen to
the excited singlet state upon excitation by a laser at 680 nm. The Acceptor
bead contains a thioxene derivative that reacts with the singlet oxygen
rapidly and undergoes a quantitative first order decay with
chemiluminescence at 370 nm, which is then transferred to the coexisting
fluorephores through typical energy transfer process to generate
fluorescence signal at 520-620 nm. Because of its short life time in aqueous
solution (~4 usec), singlet oxygen diffuses to a distance of no more than
~200 nm. We have developed 11 ALPHA assays including kinase, protease,
helicase, protein-protein, protein-DNA, PCR, SNP detection, as well as cAMP
cell-based assay. I'll present data for representative assays in 384/1536
format using 1 to 20 ul volume. This technology enables quick
miniaturization for uHTS without having to increase assay concentrations.
_______________________________________

Presentation:  A Solution-Phase High-Throughput Positional Scanning Approach
Hans-Joerg Roth

1) Positional scanning approach vs. full exploration of modular scaffolds
2) An example
3) Impact on Logistics and Infrastructure
4) Typical mistakes in parallel synthesis concepts
5) Conceptual conclusions
_______________________________________

Presentation:  COMPARATIVE STUDY ON THE FEASIBILITY OF THE ENZYME ASSAYS AND
CELLULAR REPORTER GENE ASSAYS IN YEAST IN THE 96-, 384- AND 1536-WELL PLATE
FORMAT
M. Berg, K. Undisz, R. Thiericke, S. Grabley, T. Moore* and C. Posten**
Hans-Knoell-Institut für Naturstoff-Forschung e.V., Beutenbergstr. 11,
D-07745 Jena, Germany, Tel.: ++49 3641 656926, Fax: ++49 3641 656944
* OPAL Jena GmbH, Goeschwitzerstr. 40, D-07745 Jena, Germany
** Institut für Mechanische Verfahrenstechnik und Mechanik der Universitaet
Karlsruhe (TH), Kaiserstr. 12, D-76185 Karsruhe, Germany

Today’s demands in the drug discovery process force pharmaceutical companies
to screen an ever increasing number of compounds against an increasing
amount of targets. Consequently, miniaturization of established assays has
become an advantageous means in high-throughput-screening (HTS) to meet
reagent and sample cost, turnaround and space requirements. One way to
realize this is to move from the standard 96-well plate to higher density
microplate formats.

This talk will describe the adaptation of two fluorescence-based assay
systems to the challenges of the 1536-well plate format from both the
engineer’s and biochemist’s point of view. We optimized liquid handling
parameters of the micropipetting device JOBIwellTM (Jenoptik-Bioinstruments
GmbH, Germany) using fluorescein-isothiocyanate as fluorescence dye. On this
basis pipetting routines were established for an enzyme assay
(ß-galactosidase) and a transcription assay in yeast (human progesterone
receptor, hPR) in the 384- and 1536-well format. Finally, the experimental
results were compared to those obtained in the well-established 96-well
format.

In all three assay formats, bioconversion of
fluorescein-di-ß-D-galactopyranoside occurred as a function of the
ß-galactosidase concentration (in vitro assay) and the reporter gene
expression showed the expected dependence on the ligand’s dose and affinity
(yeast transcription assay), respectively. We conclude that miniaturization
using the higher density 384- and 1536-well plate formats is advantageous as
the next evolutionary step in HTS. JOBIwellTM proves to be a powerful tool
for a careful adaptation of the liquid handling procedures.
_______________________________________

Presentation:  Combinatorial synthesis using the IRORI Accutag system
David M. Gange, Ph.D.

During my talk I will discuss our experiences with the IRORI Accutag
high-throughput synthesis system. I'll cover our use of the system, its'
strengths, weaknesses, and how we plan to use the IRORI system in the
future.
_______________________________________

Presentation:  Development of Fluorescence Polarization and FRET Assays for
Tyrosine and Serine/Threonine Kinases
Dr. Jinzi J. Wu, Senior Scientist III, Head of Assay Development and
Optimization Lab, US Lead Finding
Novartis Pharmaceuticals Corporation, Summit, NJ

Homogeneous fluorescence approaches such as FRET and FP are very important
technologies for developing effective HTS assays for discovering therapeutic
leads of kinases. This presentation will compare FRET and FP technologies
for both tyrosine and serine/threonine kinase assays in terms of
sensitivity, reliability and cost of reagents. The presentation will focus
on discovery of a high affinity anti-phosphoserine antibody and applications
of this antibody in the development of FP assays for a number of
serine/threonine kinases. The preliminary screening data will also be
discussed.
_______________________________________

Exhibitors:

Advanced ChemTech
Amersham Pharmacia Biotech
Argonaut
B-D Falcon
Beckman Coulter
Bohdan Automation
Cartesian Technologies, Inc.
CCS Packard
Corning, Inc
CRS
Gilson, Inc
Hudson Control Group
IGEN
Labsystems
LEAP Technologies
LJL BioSystems
Marsh Biomedical Products
MDL
Nalge Nunc International
NEN Life Science Products
PE-Biosystems
QIAGEN, Inc./ROSYS, Inc.
Robbins Scientific Corp.
Skatron Instruments
S-T Robotics
Tecan US
TekCel
Titertek
Tomtec
 _______________________________________

Directions (on line directions at http://marriotthotels.com/EWRHO/):
Take Route 287 to Exit 39 (Route 10 West). Go through one stoplight and take
1st u-turn. 
_______________________________________

Andy Zaayenga
Secretary, The Laboratory Robotics Interest Group
LRIG Home & Mid Atlantic Chapter
1730 West Circle Drive
Martinsville, NJ  08836-2147
Office: (732)302-1038
Fax:    (732)302-9080
eFax:   (630)604-2935
mailto:andy.zaayenga at lab-robotics.org
web site: http://lab-robotics.org
         




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