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Customer Publications and an Integrated Configuration for Drug Discovery

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Marc Goldstein, Ph.D and Angelica Olcott, Ph.D

At Beckman Coulter, our automation products for drug discovery have reached the stage where we can fully incorporate a variety of associated genetic analysis and cellular products into customer configurations that provide rapid plate handling. An Industrial Robotics Solution can provide the basis for large-scale automation of a wide range of laboratory process, be it a compound distribution or reformatting task, a sample preparation method or an assay that might require incubation and detection.

Beckman Coulter offers a range of robotic solutions to meet these needs. Shown here, our industrial robot serves as the link between the BioRAPTR FRD™, the PARADIGM™ Detection Platform and the Cell Lab Quanta™ SC MPL. Other common components include a barcode print and apply station, plate washers, Cytomat incubators and Biomek® NXP or Biomek FXP workstations. Powered by the powerful SAMI® Workstation EX, and customized for each application by our expert Integrated Solutions team, these systems provide the ultimate in process automation.

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Figure 1

Industrial Robot Accessing CellLab Quanta SC MPL. Also shown are the PARADIGM Detection Platform, BioRAPTR FRD, Print and Apply Station .
Figure 2

Biomek NXP connects to the industrial robot via a plate shuttle that allows the robot to efficiently move labware to and from the deck.

All Industrial Robotics solutions are NOT alike. In fact, each is customized for its task, while maintaining a core competency and flexibility that is derived from the long heritage of Beckman Coulter automation. In
Figure 2 we show the Biomek NXP connected to the industrial robot via a plate shuttle that allows the robot to efficiently move labware to and from the deck. Because researchers often need to use the liquid handler in "stand-alone" mode, the placement of the Biomek outside the enclosure promotes ease of use without sacrificing safety or sample integrity.  Protected by a light curtain, the Biomek can be controlled either through SAMI EX or the Biomek software.

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New Automation for Cellular Analysis

The successful development of recombinant drug therapies and stem cell technologies has added more diversity to drug discovery. Customers in biopharma, contract research organizations and academic immunology groups can benefit from configurations for complete automation of cell monitoring in their cell culture process as well as automated sample preparation of flow cytometry. We have addressed these needs with extensive automation of our cellular analysis product line.

To date, our Quanta SC MPL and FC 500 MPL instruments are in use in a number of integrated Biomek systems at customer sites worldwide. We recently introduced (at LabAuto 2008) an integration of the Vi-CELL® XR with our Biomek NXP Span-8 platform to provide fully-automated analysis of cell viability and cell sizing. These integrated systems demonstrate that we are the sole vendor that can provide an entire cellular automation solution for flow cytometry. Development of these integrated cell monitoring systems also expands the software options we provide for ELISA Assay Workstations. By combining our scheduling software, SAMI EX, with advanced data management tools, we can provide process management functions for control of long-term cell culture processes. 

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Customer Publications Highlight Automation for a Variety of Assays

In the traditional drug discovery arena, our integrated systems have aided the screening of compounds in many novel assays. To provide examples of this benefit, we summarize two recent publications from customer Marcie Glicksman, Ph.D, at Harvard Partners in Cambridge, Mass. Marcie and her team have successfully utilized a Biomek FX configuration to train post-doctoral candidates to develop neurologic drug screens that involve testing extensive compound libraries. Her integrated system contains a Biomek FX, plate transportation, plate washing/storage and detection analysis.  

In her recent publication from the Journal of Biomolecular Screening, the author and her group developed luciferase expessing neuroblastoma cells that produced the fluorescent protein under the translational control of a mRNA generated from amyloid precursor protein (APP). APP is currently hypothesized to be the key protein involved in Alzheimer’s disease. They used these cells in their high-throughput screen to determine the effect of 110,000 compounds from the library of the Laboratory for Drug Discovery on Neurodegeneration and obtained several non-toxic specific inhibitors of the APP mRNA in transfected cells.  The hits obtained from this robust screen were intended to identify agents for further evaluation of their ability to limit the stem-loop region of APP. Compound dilution for the screens was done on a Multimek 96/384 pipettor, while the transfer of compounds to cells and the resulting luciferase assay was performed on the Biomek FX integrated system.

Another 2007 publication from Marcie Glicksman in the Journal of Biomolecular Screening describes the utility of drug screens that target pathogenic T cells involved in a mouse model of Multiple Sclerosis called EAE (Experimental Autoimmune Encephalomyelitis). To identify drug-like compounds that may inhibit inflammatory T-cell responses, the authors created a high-throughput screening assay with primary T cells from PLP TCR transgenic mice. They screened 41,184 small-molecule compounds that displayed inhibitory activity on the proliferation and secretion of pro-inflammatory cytokine products from the pathogenic PLP-reactive T cells. The results of the screen identified six nontoxic and low-molecular-weight compounds that inhibited inflammatory responses in PLP-reactive T cells in a concentration-dependent fashion. The identified compounds represent valid leads that could be developed into novel therapeutics for MS and could be administered orally. During the initial screening assays, compounds were added to plates containing cells on the Biomek FX laboratory automation workstation and luminescence output was measured.

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For Research Use Only; not for use in diagnostic procedures.

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