NEW YORK (GenomeWeb) – A new study out of the University Hospital of Basel and Lund University has demonstrated that Symcel's recently launched platform for real-time bioenergetic measurements can accurately monitor the metabolic activity of tumor microtissues, bacteria, and parasitic worms, opening the door for the system's use for biomedical applications.
The platform, called calScreener, is based on the principles of microcalorimetry, using heat to measure metabolic and physical changes. Samples are deposited into 32 individual sealed cups positioned within a plate, with 16 additional wells used as quality-control references.
The plate is then placed in a thermostatic chamber set at a target temperature, and a heat-flux detecting sensor registers energy released within the cups and generates signals that are proportional to the heat flow. These signals are subsequently analyzed using software that allows a user to assign real-time data for each test well and to view the progress of all the test graphs simultaneously or individually.
Traditionally, bioassay applications of isothermal microcalorimetry have been limited by the technique's low throughput, the researchers wrote in their report, which appeared in the Biotechnology Journal.
In order to demonstrate that the calScreener's 48-well format overcomes this issue, the team evaluated the platform's ability to measure the growth of Proteus mirabilis, a gram-negative bacterium that typically infects hospitalized patients, hepatocarcinoma microtissues, and Schistosoma parasitic flatworms.
For P. mirabilis, the study showed calScreener was capable of determining both growth rate and lag phase duration, producing data consistent with conventional optical density and colony-forming unit counts.
"Potentially, the determined growth rate can be used to assess the effect of a substance on microbial growth, and the lag phase duration can be used to estimate the bacterial load in a sample or a potential bactericidal effect more quickly and as reliably than time-consuming conventional methods used for screening," the study's authors wrote. Further, the instrument can be used with opaque samples such as blood or stool where optical methods are not applicable.
With microtumor tissue and parasitic worms, calScreener proved sensitive enough to offer a similar throughput as traditional microscopy, but with a reduced workload. Additionally, "combining microcalorimetric data with other sets of data allows pinpointing of interesting time points in the heat production profile," according to the Biotechnology Journal report.
The study also pointed to calScreener's potential for biomedical research. For instance, in the study of P. mirabilis, the scientists were able to gather data on the bacteria's secreted protease activities, suggesting the platform could be used to access the production of such enzymes in other organisms and therefore be used in the screening of therapeutic protease inhibitors.
"Similarly, when considering cancer … our results show that overall viability and growth of cancer microtissues can be easily monitored over time without the need of disrupting them to perform a viability assay," the investigators noted. "Considering the high intratumor genetic heterogeneity, phenotypic screening of the susceptibility of tumors to anti-tumor agents potentially provides a cheap alternative for selecting the best possible chemotherapy and aids the development of personalized medicine based on tumor biopsies."
"The research shows that isothermal microcalorimetry is a highly versatile and user-friendly test that complements existing tools in microbiology whilst at the same time enhancing the ability to monitor metabolic activity and thereby generating highly useful results," University Hospital of Basel's Oliver Braissant, who led the study, said in a statement.