Shedding labels

Caliper Life Sciences, SRU Biosystems to offer label-free services for cell-based and biochemical assays

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WOBURN, Mass.—Caliper Life Sciences recently entered into anagreement with SRU Biosystems to use its label-free BIND technology to offernew functional assays as part of its discovery alliances and services. Underthe agreement, Caliper will use SRU's label-free BIND technology forhigh-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 andsales for Caliper Life Sciences, Caliper plans to incorporate SRU's platform incontract services it offers to the biotechnology and pharmaceutical researchcommunities.
"We are really hoping to establish the label-free method asthe way to go for cell-based GPCR," notes Mourere.
The label-free BIND technology, developed by SRU, providesresearchers with a new ultra-high- throughput screening and profiling systemfor cell-based and biochemical assays. BIND technology for cell-based assaysoffers an orthogonal screening tool to access new hits and lead molecules thatare not detected by other systems, including compounds that undergo G-proteinswitching, non-G protein coupled pathways, inverse and partial agonists andreceptor desensitization.
The screening platform is robust and can be applied to bothover-expressed and endogenous receptors, and can be used with low numbers ofprimary cells. The technology can also used for receptor profiling on nativecells, due to the high sensitivity of the response. Lastly, the BIND technologyprovides a way to easily screen Gi-coupled GPCR targets and ion channels, whichhave been traditionally difficult to assess.
Dr. Rick Wagner, president and CEO of SRU, says Caliper LifeSciences is an excellent partner for SRU.
"They are uniquely positioned to offer BIND technology as acontract service to the biotechnology and pharmaceutical communities," hepoints out. "They have tremendous knowledge utilizing innovative technologiesto advance drug discovery and will provide an outstanding new service to thedrug discovery industry."
SRU Biosystems' label-free BIND technology can be used forcomplex cellular assays such as GPCR pathway analysis, ion channel assays andcell adhesion assays; as well as biochemical assays, such as protein-proteinbinding, enzyme assays and fragment and small molecule screening. Theseapplications have been utilized in exploring assay development, 1536-well highthroughput screening and lead profiling. SRU anticipates a continued expansionof its label-free BIND products, creating new assay capabilities.
Mourere says SRU Biosystem's BIND Reader provides aflexible, label-free detection system that the company can use to perform both invitro biochemical assays as well asfunctional cell-based assays.
According to Mourere, assays that use labeled components arecommon in drug discovery, but labels have disadvantages.
"They can disrupt natural binding, require time consumingand costly modifications to original assay components, and may not accuratelycapture all aspects of the pharmacology of a receptor signaling pathway," henotes. "The BIND label-free technology offers distinct advantages and allowsfor the detection of in vitro biochemical assays (e.g. protein-drug,protein-protein), and cell-based assays without the need for conventionallabels."
For biochemical assays, Mourere notes that measuring directbinding of a ligand to its protein target provides necessary information forchemists to advance drugs through the discovery process. 
"Researchers use NMR and X-ray crystallography to get directbinding data, but because these methods are low-throughput, they can only beused on a small number of compounds further down in the drug discoverypipeline," he says. "SPR has been another common technology used to obtaindirect binding data. While it provides important affinity information, thetechnology does not have the throughput capabilities to be used as a primaryscreening platform."
Furthermore, the microfluidics of SPR systems make themsusceptible to aggregating or promiscuous binding compounds, he adds.
"The plate-based BIND Reader provides direct binding data ina very high-throughput platform and easily identifies aggregating compounds inone assay," Mourere points out. "This allows scientists to eliminate non-binderand aggregating compounds from their library early on in the pipeline. The BINDReader is a complementary technology and fills the gap between uHTS enzymaticassays and lower throughput SPR and NMR assays."
With cell-based assays, the BIND technology provides aflexible platform to perform functional cell-based assays on a range of surfacereceptor target classes (e.g. GPCRs, ion channels, RTKs) in a variety ofbackgrounds. 
"Because the label-free technology requires no labels, celllines do not require the extensive modification necessary for more traditionalassays. This greatly simplifies assay development," Mourere says. "Researcherscan easily assay receptors over-expressed in cell lines (both adherent andsuspension), and then immediately validate those hits in more physiologicallyrelevant cell lines with endogenous receptors, and then primary cells using thesame BIND platform. Because the label-free technology provides a whole cellresponse, the system is ideal for compound profiling and pathwayanalysis." 
Mourere points out that label-free detection is a powerfulnew technology in drug discovery research, but the adoption of new technologytakes time and validation.
"The SRU and Caliper partnership will make the label-freetechnology more accessible to the drug discovery research community," he notes."It will allow researchers to validate the technology with little risk andexpand the potential applications for the technology. Caliper customers havenow access to a broad range of label-free contract research servicesencompassing custom assay development or screening compounds libraries in agrowing number of catalog assays."

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