ST. LOUIS — SRU Biosystems, Corning, and MDS Analytical Technologies debuted improvements to current label-free technology platforms at the Society for Biomolecular Sciences 14th Annual Meeting here, where a session was dedicated to the use of label-free detection in high-throughput screening and lead validation.
At the meeting, SRU launched its Cartridge Reader, based on 8- and 16-well biosensors, Corning debuted its Epic liquid-handling accessory, or LHA (see CBA News, 4/4/08), while MDS Analytical Technologies launched its CellKey 384, the latest version of its two-year-old CellKey system.
Label-free technology is useful for looking at changes in cell adhesion, cell morphology and the cellular cytoskeleton, and cell proliferation and cell death, said Lance Laing, a scientist at SRU Biosystems, during a presentation at SBS this week.
“With this technology, no labels are required; you are looking at cellular activity in real time, and because it is non-destructive, you can observe the cells over a period of many days,” Laing said. He added that these characteristics are important for studying biological functions like axon growth and neurite elongation.
“The cells are still alive when you are finished,” said Laing.
Ron Verkleeren, business director for Corning’s Epic system, said the Epic LHA is a 384-channel pipettor designed to integrate with the Epic system. The aspirator/dispenser has a working volume of 0.1 µL to 25 µL per well, and fills and transports a 384-well plate in 30 seconds.
The LHA’s plate stacker can accommodate 20 lidded 384-well Epic microplates or source plates, maintains thermal stability, and includes an automatic tip-washing station.
In an interview with CBA News, Verkleeren said that Corning has seen interest in its Epic system on the part of both biopharma and academic researchers.
Debra Gallant, product marketing manager for MDS, told CBA News that the CellKey 384 system uses a 384-well format, while the original CellKey uses a 96-well format.
CellKey is a label-free cellular analysis platform based on cellular dielectric spectroscopy. In this technique, cells are grown on electrodes embedded in microwell plates, and a constant low-level voltage is applied. A detection instrument senses changes in electrical impedance that result from changes in cell morphology, confluence, adherence, and interaction
According to SRU Biosystems’ Laing, cell biologists tell him they need to know whether the cellular response they are witnessing is dose-dependent, whether it is highly reproducible, and that there is some specificity of the signal for the target during the drug interaction.
“The cells are still alive when you are finished.”
Unfortunately, to date, label-free biosensors have required more than 20,000 cells per 384-well plate and have provided little information about how cells respond to compounds, particularly at the single-cell and small cell-cluster level, he said.
Laing presented label-free, high-resolution (4 to 80 µm) cell data collected from high-density, microplate format sensors. The data were generated from primary and parental cell lines and provided details on focal adhesion and other cell-adhesion properties, chemotaxis, cell migration, neuronal cell growth, and cell interaction with extracellular matrices from fewer than 300 cells per well.
Laing said that he and his team were able to measure high resolution, label-free response to compound treatment for intracellular targets.
“One of the ways that we are looking at solving the problem of lower cell numbers is going to a higher-density plate, which means a smaller sensor area, and using a 1,536-well format,” Laing said.
In a 1,536-well format and with the addition of carbachol, the SRU scientists used about 8,000 TP1 cells per well, which is “interesting, but not exceptional,” as Laing put it. “We did get tight, reproducible responses for these dose curves, however, and the data agrees very well with the sensitivity of the 384-well format.” TP1 cells are 7 µm in size.
The SRU team then tried to reduce the number of cells per well even further. “Down to an average of 600 cells per well, the errors bars were still rather tight,” said Laing.
“If you want to go into the human primary cells you might want to go into even lower amounts, 50 to 100 cells per well,” he said.
However, some feel that while label-free technologies have promise, they are not a magic bullet for the drug discovery or cell-based assay markets.
According to Cellumen CEO and President Lansing Taylor, although label-free technologies are useful for certain cell-based applications, particularly G protein- coupled and tyrosine kinase receptors, their inability to multiplex and the lack of molecular specificity means that they have relatively limited value.
Cellumen offers cellular systems biology-based compound profiling services and licenses for cell lines, reagents, and multiplexed assays for drug discovery.
However, Richard Eglen, president of biodiscovery for PerkinElmer, said, “We are watching the label-free market very carefully. We will be interested to see how the technology matures, and if can make the leap from secondary screening and lead optimization to primary high-throughput screening.”