How High-Tech Streams into the Discovery Process at Monsanto
Spin the Bottleneck
Introduction (Back to Top)
Molecular Devices Corporation(Sunnyvale, CA) and CRS Robotics Corp. (Toronto) have installed a state-of-the-art lab automation system at Monsanto (St. Louis) that combines LJL's Analyst HT assay detection system with CRS's robotics technology and Polara lab automation software. Monsanto's newly designed system further automates the tedious but critically important process of screening potential drug candidates for development into commercial products. It also supports both 96-well and 384-well assay formats in LJL's Analyst environment.
Combining detection and robotics technologies reflects a trend among leading drug houses towards maximum throughput and flexibility in their discovery efforts, according to LJL.
"Monsanto is another major company that selected LJL's Analyst system as a solution for both assay development and screening," said Lev Leytes, president and CEO of LJL. "For leading companies that understand the value of workstation-based screening with maximum flexibility, the partnership of LJL technologies with robotic technology from CRS represents a powerful solution in both high-throughput screening (HTS) and ultra high-throughput screening (UHTS). We believe this high-tech approach demonstrates how a competitive, research-based company like Monsanto may improve its assay screening systems, leading to a more flexible and more accelerated HTS process."
How High-Tech Streams into the Discovery Process at Monsanto (Back to Top)
As part of LJL's Criterion family of HTS products and services, Analyst is capable of reading multiple assay formats such as fluorescence intensity, fluorescence polarization, time-resolved fluorescence, and luminescence. CRS's Open Architecture Lab Automation Software, Polara, integrates robotic automation with LJL's Analyst and other 96/384 well instrumentation already in place at Monsanto. Polara provides methods development, scheduling, runtime monitoring, error handling, and recovery for the entire system. The modular table design allows operators to make changes in either instrumentation or assays quickly and easily.
"The flexibility to make changes without compromising the full expediency of high throughput screening is what we value most," said Marshall Michener, specialty subgroup leader at Mosanto. "Our assay requirements are always changing because of the broad range of therapeutic drug discovery programs at the company. The CRS lab automation system with Polara software, combined with LJL's Criterion Analyst will yield significant benefit to us."
Analyst HT (Back to Top)
Like LJL's Analyst AD (used for assay development), Analyst HT works in all major non-radioactive assay detection modes used in HTS, including fluorescence intensity, high-efficiency fluorescence polarization, time-resolved fluorescence, epiabsorbance, and luminescence. Both AD and HT systems use SmartOptics, a detection protocol optimized for both 96-and 384-well formats. SmartOptics is designed to optimize sensitivity, dynamic range, signal-to-noise, and crosstalk across multiple detection modes. Sharing a common platform for assay development and screening eliminates the need to modify and re-validate assays upon their transfer from assay development into HTS.
LJL was prompted to develop the HT system because of its earlier success with AD. Customers thought very highly of HT, according to LJL marketing manager Mike Biros, and were eager to use the same platform for screening as for assay development.
"Analyst HT is the first versatile, multi-detection system specifically designed for HTS using microplate readers designed for standard bench-type use," Biros said. "In the past, companies that tried to integrate microplate readers into their HTS lines were frustrated because of poor performance, reliability, and a lack of automation. Keep in mind that most of these systems were designed to run several plates a week, and manually at that. When the automation people tried to stick these readers onto robotic line, robots had difficulty placing plates into system. Plus there was no software support for passing commands to a robot, a problem that became most evident during a malfunction. And even when they worked, none of these systems had the capability to run several plates a day. When combined with a good robotics system, Analyst HT can process 200 plates per day in fully automated mode, plus it can switch among five detection modes without requiring the end-user to open up the box."
Spin the Bottleneck (Back to Top)
Before the emergence of automated, parallel synthesis, most discovery chemists would agree that making compounds was the most serious bottleneck in discovering new drugs. With the advent of combinatorial libraries and high-throughput synthesis, screening became the rate-limiting step in drug discovery. According to Biros, HTS technology has now improved to the point where upstream and downstream activities have replaced screening as the slow steps. "We now have the technology to screen everything pharmaceutical companies make," Biros stated. "Not everyone has implemeted the latest technology, but it's out there if they want it. What's slowing the industry down now is [upstream] screen development and [downstream] lead followup, secondary screening, and lead optimization."
LJL BioSystems (Back to Top)
LJL BioSystems Inc. develops, produces, and markets to pharmaceutical and biotechnology firms products and services that accelerate and enhance drug discovery. LJL's proprietary technology platform is designed to address many of the limitations associated with current HTS products. LJL customers include Bristol Myers Squibb, Eli Lilly and Co., Aurora Biosciences Corp., Tularik Inc., Millennium Pharmaceuticals Inc., Dupont Pharmaceuticals Co., Amgen Inc., Monsanto Co., and Pharmacia & Upjohn.
CRS Robotics (Back to Top)
CRS Robotics is an automation company specializing in standard lab automation products for biotechnology and pharmaceutical research applications. In addition, CRS supplies robots to niche advanced manufacturing markets.
For more information: Michael Biros, Marketing Manager, LJL BioSystems Inc., 404 Tasman Dr., Sunnyvale, CA 94089. Tel: 408-541-8761. Fax: 408-541-8786.
By Angelo DePalma