The Laboratory Robotics Interest Group

February 1998 Meeting

Drug Discovery

Date:        Wednesday, February 25, 1998
Place:       Somerset Marriot Hotel, 110 Davidson Avenue, Somerset, NJ 08873
                 Phone: 732-560-0500    Fax: 732-560-3669
Itinerary:  Social Period with hors d’oeuvres and Vendor Exhibition, 4:30 to 6:30 pm
                 Presentations, 6:30 to 9:00 pm
Pre-Registration: not required

Agenda:  This meeting will address the topics of Combinatorial Chemistry, Compound Distribution and Ultra High Throughput Screening.  During the Social Period which will feature hors d’oeuvres and a cash bar, there will be a Vendor's Exhibition.  Following will be four presentations, with question and answer periods.  Members interested in presenting a poster during the Social Period are encouraged to do so.  Open career positions at your company may be announced or posted.  There is no fee to attend the meeting.

Presentation: Massively Parallel, Microfabricated Systems for High-Throughput Drug Discovery
Sheila H. DeWitt
Orchid Biocomputer
201 Washington Road, Princeton, NJ 08543-2197

A microfluidic, chip-based system for the integration of high-throughput drug discovery efforts has been developed and demonstrated as a collaborative effort between SmithKline Beecham and Orchid Biocomputer. The applications include all areas of preclinical drug discovery including combinatorial chemistry, ultra high-throughput screening, genomics, drug metabolism, and toxicology. The microfluidic chip incorporates microfabricated components for valving and pumping of fluids, within a three-dimensional fluidic network. The pumping and valving mechanisms have no moving parts, making large scale integration feasible and inherently reliable. Key aspects of the highly integrated electrokinetic transport of fluids, and representative examples including the transport of organic solvents and reagents will be presented.

Presentation: UHTS: The New Challenge of the Sample Dispensary
Eric W. Kaldy
The Automation Partnership
9 Blueberry Hill Reserve, Killingworth, CT 06419

In the past few years there has been an explosion of new chemical entity generation and biological target identification. This push coupled with the pull of the business need to fill the product pipeline faster has created a new technology, Ultra High Throughput Screening (UHTS). The realization of UHTS throughputs 100,000 or more assays per day places new demands on the compound dispensary. How do you store & retrieve, prepare, and dispatch libraries of 50,000 - 2,000,000 compounds for UHTS, HTS, and therapeutic biology assay testing while maintaining sample and data integrity? How do you achieve both high throughput and flexibility? This talk identifies the critical issues associated with dispensary management and automation logistics.

Presentation: MOBA: An Ultra-High Throughput Screening Platform For Lead Generation, Characterization, and Optimization
Frank H. Michaels, Ph.D.
Research Director, The Biotechnology Laboratories at Thomas Jefferson University
Director of Research, GEM Array Biosciences.

A cell based, ultra-high throughput screening platform technology capable of operating in a completely automated micro-miniaturized environment is being developed. This technology employs Genetically Engineered Microorganisms (GEMs) designed to detect biochemical interactions of pharmacological importance. Because the screening system employs whole viable cells, toxic compounds are detected and deleted from future development. Additionally, because intracellular availability of lead compounds is required for assay activity, poorly absorbed compounds are identified. Assay cycle times are less than 2 hours, and micro- to nanomolar ED50s can be detected. New assay development commonly requires less than 8 weeks, and subsequent lead optimization entails significantly less time. This novel technology can detect protein-protein, RNA-protein and DNA-protein interactions allowing the generation of arrays of microminiaturized assays to define medically important candidates from combinatorial libraries or assemblies of crude extracts for lead identification and optimization.

Presentation: HTS-Factory ?: An Industrial Approach to High Throughput Screening
Ernst Burgisser
Discovery Technologies, Inc.
Switzerland

The enormous demand for rapid and cost-effective performance of high throughput screening (HTS) is calling for novel concepts in automation and logistics. Discovery Technologies Ltd., a newly founded service and technology company, provides custom-oriented HTS and follow-up services. An HTS-Factory?has been designed to process up to 100,000 tests (which is equivalent to 1,200 96-well microplates) within one working day. Higher density formats can be implemented, as long as they fit the standard microplate footprint, yielding a multiplication of throughput. In contrast to well-established laboratory automation solutions, the HTS-Factory concept is based on industrial handling technology , which has proven to be very reliable, fast and cost-effective for more than two decades.

The key elements of the HTS-Factory are: 1.) fully automated storage and retrieval system for chemical libraries, pre-plated in 96-well microplates and kept under dry and inert atmosphere; 2.) all the microplate handling is done in stacks of ten plates; 3.) a newly designed plate stacker is capable of presenting all plates within less than a minute to liquid handlers, incubators, and readers; 4.) several 96-channel pipetters are working simultaneously; 5.) the plates stacks are transported on a fast conveyor system with individual shuttles; 6.) all plates are bar-coded, allowing perfect tracking and quality assurance. Further to the high throughput mode, the system prepares assay plates for upcoming HTS projects, compound mixture plates ("matrix cocktail"), plates for verification assays as well as preparation of microplates for EC-50 determination in a fully automated and unattended 24-hour mode.

Exhibiting Vendors

For more information contact:

From Route 287 Traveling North: From Route 287 Northbound, take exit 10 (Route 527/New Brunswick/South Bound Brook).  Follow Route 527 North to the first traffic light and make a left (Davidson Avenue).  Hotel is 2nd building on the left, second driveway entrance.  Hotel is adjacent to Garden State Exhibit Center.

From Route 287 Traveling South:  From Route 287 Southbound, take exit 10 (Route 527/Easton Avenue/New Brunswick).  At the bottom of the exit ramp get immediately into the left lane and make a left hand turn.  (Go under the underpass of Route 287).  Once you have turned left, go straight (bearing to your right - 527 North) to the first traffic light and make a left onto Davidson Avenue.  Hotel is 2nd building on the left, second driveway entrance.  Hotel is adjacent to Garden State Exhibit Center.

From New Jersey Turnpike:  Take Exit 10 to Route 287 North.  Follow directions from Route 287 North.

From Garden State Parkway Traveling North:  Take Exit 127 to Route 287 North.  Follow directions from Route 287 North.

From Garden State Parkway Traveling South:  Take Exit 129 to Route 287 North.  Follow directions from Route 287 North.

From Newark Airport:  Take the New Jersey Turnpike South to Exit 10 to Route 287 North.  Follow directions from Route 287 North.

From J.F.K. Airport and the Brooklyn Area:  Take the Belt Parkway to the Verrazano Narrows Bridge.  Over the bridge take the Staten Island Expressway (Outer Bridge Crossing) to Route 440 West.  Follow 440 West to Route 287 North.  Follow directions from Route 287 North.

From LaGuardia Airport:  Take the Grand Central Parkway to the Brooklyn-Queens Expressway.  Follow to the Verrazano Narrows Bridge.  Over the bridge take the Staten Island Expressway (Outer Bridge Crossing) to Route 440 West.   Follow 440 West to Route 287 North.  Follow directions from Route 287 North.

From Philadelphia:  Take the New Jersey Turnpike North to Exit 10 to Route 287 North.  Follow directions from Route 287 North.

From Mid-town Manhattan:  Take either the Holland or Lincoln Tunnel to the New Jersey Turnpike (95) South.  Take Exit 10 to Route 287 North.  Follow directions from Route 287 North.

From Upstate New York/New England:  Take the New York Thru-way to the Garden State Parkway.  Go South to Exit 129 to Route 287 North.  Follow directions from Route 287 North.

From Princeton Area:  Take Route 202-206 North to Route 22 East to Route 287 South.  Follow directions from Route 287 South.   -  or -    Route 1 North to 287 North.  Follow directions from Route 287 North.

Sponsors: We are extremely grateful to Corning Inc., Hewlett Packard, and Perkin-Elmer Tropix for sponsoring this meeting and contributing towards the hors d’oeuvres and mailing costs.

Long acknowledged for our expertise in surface chemistry and materials science in polymers and glass, Corning Costar continues to advance innovative solutions for today’s emerging life science trends. We are the industry leader in plastic vessels for cell culture and liquid handling. We are also developing leading-edge products for the field of molecular biology. You can continue to look to Corning Costar for the highest standards in product design and plastics molding, as well as expanding our technology to include encapsulation of membranes into plastic devices. We’ve enhanced our offering of products and their packaging to be robotics-and automation-friendly, and are furthering our efforts to produce environmentally sensitive materials.

Hewlett-Packard is pleased to sponsor this meeting of the Laboratory Robotics Interest Group. Since 1965, HP technology has given the scientific community advances in chemical analysis, such as the electronic-recording integrator, the microprocessor-controlled analytical instrument, the C-terminal protein sequencer, capillary electrochromatography, the digital benchtop gas chromatograph/mass spectrometer and the fused-silica capillary column.

HP understands the benefits that automation can provide and is committed to helping chemists in all fields of scientific endeavor become more productive. We are a pioneer in automation, having introduced the first GC autoinjector in 1969. That same innovative spirit continues today with autosamplers for GC and LC, automated systems for combinatorial chemistry analysis, and the HP 7686 Solution-Phase Synthesizer.

The HP 7686 Solution-Phase Synthesizer automates organic synthesis and cleanup for lead optimization. It can create hundreds of analogs a week in quantities sufficient to meet screening, characterization, and archiving needs. Using the HP synthesizer, medicinal chemists can spend their time investigating more complex or novel chemistries.

For more information about Hewlett-Packard products and services, visit us on the World Wide Web at http://www.hp.com/go/chem.

Tropix is a leader in the development manufacture and sale of products and services based on luminescent technology. Tropix continues to advance luminescence technology with ongoing developments to the chemistry and instrumentation. To date, Tropix has over 200 patents and patent applications and is referenced in hundreds of published papers. With the TR717 microplate luminometer, Tropix advances a complete luminescent solution for highly sensitive detection of bio-analytes. The TR717 can detect zeptomole concentrations of analytes, can be used with 96 or 384 well plates, and is available in a fully robotics compatible version. Tropix has recently expanded it product offering to include the establishment of an assay development service focused on the creation of superior performing assays specifically formatted for high throughput screening. Tropix products and services are further strengthened by parent company Perkin-Elmer and its Applied Biosystems division, the leader in life science systems and instrumentation.

Group Update:  The LRIG in partnership with the Society for Biomolecular Screening (SBS) has created a working group to specify a common set of software modules for bi-directional communication with High Throughput Screening instruments.  The overall goals are:
1) Create a common software module or modules to acquire data output from instruments into Oracle databases (possibly set some standards).
2) Create a standard API and a common software module or modules for instrument control.
There is good representation of automation providers and integrators in the group.  We would like to have more representation for instrument (readers, etc.) manufacturers and end users.  For more information on how to participate please contact LRIG Secretary Andy Zaayenga.

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