Where the hardware meets wetware

FARMINGDALE, N.Y.—With the goal of providing researchinstitutions and biotechnology and pharmaceutical companies with acost-effective, high-performance platform for live cell analysis, Enzo BiochemInc. and BioTek Instruments Inc. have entered into a co-marketing partnershipthat integrates instruments and reagent solutions.

The co-marketing agreement combines the state-of-the-artfluorescent labeling and detection capabilities of Enzo's Life Sciencessubsidiary with BioTek's expertise in advanced liquid handling and fluorescencequantification, producing an efficient workflow in which both hardware and"wetware" work in concert to augment each other. The two teams will workclosely together, with both groups simultaneously benchmarking theinstrumentation and reagents in their respective laboratories. Enzo willdevelop the fluorescent assay technology, while BioTek will optimize theirperformance on the Synergy Mx instrument.

In the short term, the companies' goal is to provide a newparadigm for compound screening and optimization in GPCR-based drug discovery.Longer range, the Enzo-BioTek collaboration aims to provide a panel offluorescence-based live cell assays optimized for advanced microplate-basedanalytical readouts. Financial terms of the agreement were not disclosed.

The partnership was both born and launched on the industryconference circuit. According to Dr. Wayne Patton, Enzo's chief scientificofficer, the companies' first discussions occurred in April at the 2009 Societyof Biomolecular Screening (SBS) meeting in Lille, France. BioTek scientistswere presenting a poster on their Synergy Mx monochromator-based microplatereader, while Enzo scientists were presenting one on their new Lyso-ID Redfluorescent cell-based cytotoxicity assay.

"We both appreciated that merging novel cell-based assayswith a high-performance microplate reader would provide a powerful combinationof attributes for customers interested in drug discovery and cytotoxicityscreening," Patton says.

The collaboration was formally launched in mid-October atMipTec 2009 in Basel, Switzerland, with the presentation of the scientificposter, "A cost-effective workflow for high-throughput screening ofG-Protein-Coupled Receptors (GPCRs)." The poster details the use of Enzo's newFluoForte Calcium Assay Kit for monitoring intracellular calcium mobilizationwith BioTek's Synergy Mx Monochromator-based Multi-Mode Microplate Reader.

For BioTek, working with Enzo was part of its strategy ofraising awareness of its instrument capabilities and the advantages of variousreagent technologies by engaging in numerous collaborative projects withvarious reagent vendors that cover all the company's products, says GaryBarush, BioTek's director of marketing and sales.

"We have extensive collaborations with Promega, Invitrogenand Millipore, resulting in numerous conference posters, application notes,technical bulletins, peer-reviewed publications and co-marketing activities,"Barush says. "We engaged Enzo Biochem as another collaborative partner due totheir interest in developing new proprietary live cell assays for microplateinstrumentation. Both companies realized that many cell based assays, such asGPCR screening assays, are not accessible to smaller biotech and pharmacompanies, or to academic laboratories, due to the very high entry costassociated with purchase of fluorescent imaging plate readers, such as theFLIPR and FDSS instruments."

The real synergy in the partnership is expertise in bothinstrumentation and reagents, as well as a commitment to integrating both intohigh-performance workflows that provide strong analytical capabilities to cellanalysis, Barush says.

"We believe that modest levels of compound screening can beachieved with a simpler and lower-cost instrument, such as the Synergy Mxinstrument, combined with high-performance reagents, such as Enzo's FluoFortecalcium assay, to effectively meet customer needs," he adds. "A major source offrustration for many researchers has been that selected assays were notcompatible with a particular instrument, and vice-versa. Our companies each provide keyexpertise and capabilities in the live-cell analysis arena, bringing togetherBioTek's capabilities in microplate detection and dispensing technology thatmatches perfectly with Enzo's cutting-edge live cell analysis reagents andkits. The result is a 'turnkey' instrument/reagent system which has beenfine-tuned for optimum performance."

Patton notes that historically, many assays performed in thedrug discovery area have involved endpoint approaches using fixed cells.However, many pharmaceutical companies are now gravitating towards live-cellassays, including the use of primary cells, tissues and even small animals,like zebrafish, especially for toxicology applications, he points out.

"Live cell analysis offers two main advantages: First, itprovides a streamlined workflow that does away with the overhead of permeabilization,fixation and secondary antibody incubation steps. Second, it offers theopportunity to perform real-time kinetic analysis," Patton says. "This isalready well-accepted practice for certain benchmark assays, such as calciummobilization, cell cycle, cell migration and wound healing assays. Thechallenge is to increase the number of assays that can be performed in a livecell context. While probably less than a quarter of all cell-based studies inthe pharmaceutical industry are currently performed using living cells, we feelthat live cell analysis will ultimately be necessary to provide the requisitedetail needed to understand complex dynamic cellular processes."

Ultimately, the partnership will provide a range of tools tohelp pharmaceutical and biotech companies optimize their preclinical andclinical drug development programs through early lead drug identification, leadcandidate selection, predictive toxicology and compound characterization,Barush concludes.

"Toxicity continues to be responsible for more than 30percent of compound attrition during the drug development process, and remainsone of the major causes for drugs being withdrawn after their approval," henotes. "Our assay workflows will provide robust and rapid in vitro toxicity screening approaches to identify compoundliabilities and STR (structure toxicity relationship) associated with newchemical entities (NCEs), aiding in selection and optimization of NCEs in theearly stages of drug discovery. The results obtained from a menu of assays onour instrument, with accompanying dose-response profiles, will provide betterunderstanding of the potential toxicity of compounds, and thus, facilitateselection of compounds with the highest probability of success."