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Shedding labels
December 2009
by David Hutton  |  Email the author


WOBURN, Mass.Caliper Life Sciences recently entered into an agreement with SRU Biosystems to use its label-free BIND technology to offer new functional assays as part of its discovery alliances and services. Under the agreement, Caliper will use SRU's label-free BIND technology for high-throughput screening and profiling for cell-based and biochemical assays. Financial terms of the agreement were not released.
According to Philippe Mourere, director of marketing and sales for Caliper Life Sciences, Caliper plans to incorporate SRU's platform in contract services it offers to the biotechnology and pharmaceutical research communities.  
"We are really hoping to establish the label-free method as the way to go for cell-based GPCR," notes Mourere.  
The label-free BIND technology, developed by SRU, provides researchers with a new ultra-high- throughput screening and profiling system for cell-based and biochemical assays. BIND technology for cell-based assays offers an orthogonal screening tool to access new hits and lead molecules that are not detected by other systems, including compounds that undergo G-protein switching, non-G protein coupled pathways, inverse and partial agonists and receptor desensitization.
The screening platform is robust and can be applied to both over-expressed and endogenous receptors, and can be used with low numbers of primary cells. The technology can also used for receptor profiling on native cells, due to the high sensitivity of the response. Lastly, the BIND technology provides a way to easily screen Gi-coupled GPCR targets and ion channels, which have been traditionally difficult to assess.  
Dr. Rick Wagner, president and CEO of SRU, says Caliper Life Sciences is an excellent partner for SRU.  
"They are uniquely positioned to offer BIND technology as a contract service to the biotechnology and pharmaceutical communities," he points out. "They have tremendous knowledge utilizing innovative technologies to advance drug discovery and will provide an outstanding new service to the drug discovery industry."
SRU Biosystems' label-free BIND technology can be used for complex cellular assays such as GPCR pathway analysis, ion channel assays and cell adhesion assays; as well as biochemical assays, such as protein-protein binding, enzyme assays and fragment and small molecule screening. These applications have been utilized in exploring assay development, 1536-well high throughput screening and lead profiling. SRU anticipates a continued expansion of its label-free BIND products, creating new assay capabilities. Mourere says SRU Biosystem's BIND Reader provides a flexible, label-free detection system that the company can use to perform both in vitro biochemical assays as well as functional cell-based assays.
According to Mourere, assays that use labeled components are common in drug discovery, but labels have disadvantages.
"They can disrupt natural binding, require time consuming and costly modifications to original assay components, and may not accurately capture all aspects of the pharmacology of a receptor signaling pathway," he notes. "The BIND label-free technology offers distinct advantages and allows for the detection of in vitro biochemical assays (e.g. protein-drug, protein-protein), and cell-based assays without the need for conventional labels."  
For biochemical assays, Mourere notes that measuring direct binding of a ligand to its protein target provides necessary information for chemists to advance drugs through the discovery process.   
"Researchers use NMR and X-ray crystallography to get direct binding data, but because these methods are low-throughput, they can only be used on a small number of compounds further down in the drug discovery pipeline," he says. "SPR has been another common technology used to obtain direct binding data. While it provides important affinity information, the technology does not have the throughput capabilities to be used as a primary screening platform."
Furthermore, the microfluidics of SPR systems make them susceptible to aggregating or promiscuous binding compounds, he adds.
"The plate-based BIND Reader provides direct binding data in a very high-throughput platform and easily identifies aggregating compounds in one assay," Mourere points out. "This allows scientists to eliminate non-binder and aggregating compounds from their library early on in the pipeline. The BIND Reader is a complementary technology and fills the gap between uHTS enzymatic assays and lower throughput SPR and NMR assays."  
With cell-based assays, the BIND technology provides a flexible platform to perform functional cell-based assays on a range of surface receptor target classes (e.g. GPCRs, ion channels, RTKs) in a variety of backgrounds.   
"Because the label-free technology requires no labels, cell lines do not require the extensive modification necessary for more traditional assays. This greatly simplifies assay development," Mourere says. "Researchers can easily assay receptors over-expressed in cell lines (both adherent and suspension), and then immediately validate those hits in more physiologically relevant cell lines with endogenous receptors, and then primary cells using the same BIND platform. Because the label-free technology provides a whole cell response, the system is ideal for compound profiling and pathway analysis."   
Mourere points out that label-free detection is a powerful new technology in drug discovery research, but the adoption of new technology takes time and validation.
"The SRU and Caliper partnership will make the label-free technology more accessible to the drug discovery research community," he notes. "It will allow researchers to validate the technology with little risk and expand the potential applications for the technology. Caliper customers have now access to a broad range of label-free contract research services encompassing custom assay development or screening compounds libraries in a growing number of catalog assays."
Code: E120916



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