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Label-Free Technologies: What’s All the Fuss?

Kevin Lustig on November 10, 2009

I attended the Society for Biomolecular Sciences Label-Free Symposium in San Diego last week. The area seems to be growing quickly, as it utilizes diverse technologies to facilitate more biologically relevant biochemical and cell-basedassays. The benefits include shorter assay development time, less interference from labeling or non-native cells, the ability to study live cells, and access to kinetic data. Additionally, the technologies can be used for applications such as fragment-based drug discovery and for analyzing protein-protein interactions.

Some of the take home messages from the symposium centered around the fact that more comprehensive, biologically relevant information can be collected more easily with label-free technologies. Some talks pointed out that the information can be less ‘binary’ than the hit/no hit answers we’re used to getting from high throughput screening (HTS), meaning that more information can be gleaned, but that more sophisticated data analyses may be needed. Although the conference appeared to feature a whirlwind of technologies, from calorimetry to optical biosensors to mass spectrometry, the same targets kept re-emerging (GPCRs, 7TMs). Thus, there is a common theme to these tools: they give us information that was difficult to obtain before.

How do the technologies work? There is no single answer, because they are so diverse, but basically they measure molecules interacting or cellular phenomena by detecting perturbations in the system. For example, optical biosensors used with surface plasmon resonance (SPR) detect a change in the refractive index when a protein binds a small molecule or protein, for biochemical/protein assays. For some label-free cell-based assays, a change in impedance is used to detect changes in cell morphology, adhesion, or viability. Check out this presentation from Corning (PDF) which shows how their Epic© System works and can discern between different GPCRs and types of effectors.

Many of the talks at the SBS symposium were from drug discovery scientists from pharma/biotech, and each speaker usually focused on a particular instrument. At first, this made the conference feel as if it was too ‘sponsored,’ but I think it might just be the nature of the industry, as most have a ‘favorite’ instrument. Here is a table outlining the companies/instruments that appeared to ‘shine’ at the conference. Interestingly, Biacore/GE Healthcare did not exhibit or present at the conference, although their instruments have been a mainstay in SPR.

Company/Instrument Technology Biochemical Cell-based
Corning Epic System Optical Biosensor Yes Yes
MDS CellKey™ System Impedance   Yes
Fujifilm AP-3000 Optical Biosensor Yes No
SRU Biosystems BIND© Platform Optical Biosensor Yes Yes

What is the drug discovery 2.0 connection with label-free technologies? Reports on both cell-based and biochemical label-free technologies predict a significant impact for drug discovery (links are to summaries – full reports must be purchased). A Drug Discovery World summary of the cell-based report detailed that the most impacted areas are likely to be hit identification and lead optimization. Some nice reviews exist in the literature, as well as this freely available one I found. Label-free technologies have the potential to streamline and standardize assay development for different targets and also provide an orthogonal, rich source of information that complements existing methods. Improvements in throughput, for example as seen with the Fujifilm AP-3000 instrument for SPR, mean that larger numbers of correlations are now possible.

Does the Scientist marketplace offer label-free assay services? We’re not aware that any of our providers specialize in these types of assays, but we spoke to several companies at the conference and got a great response. Stay tuned!