Microcalorimetry assay opens new research avenues

Assay developer SymCel has announced the publication of positive scientific data on its microcalimeter technology calScreener - said to be the first multichannel calorimetric system specifically developed for cell-based assays. The technology quantifies the metabolism of tumourous micro tissues, bacteria and worm parasites.

The label-free and passive nature of isothermal calorimetry makes possible accurate measurements on complex 3D structures, like micro tissues, solving the problem of conventional assays which can’t be performed without the destruction of the 3D structured micro tissues concerned. The calScreener system, equipped with a vessel holder similar to a 48-well plate, provides increased throughput for use in bioassays.

Studies published in The Biotechnology Journal indicate that heat production rates by the living organisms tested were sufficient to produce detectable signals over time. The isothermal microcalorimeter also provided reproducible and accurate data. The findings open up multiple new research avenues across cancer research, diagnostics and the development of antitumour drugs.

The screening approach, when applied to the susceptibility of tumours to antitumour agents, is said to provide an alternative for selecting the best possible chemotherapy and aid the development of personalised medicine based in tumour biopsies, due to the high intra-tumour genetic heterogeneity. The results show that the technology can easily monitor the overall viability and growth of cancer micro tissues over time without any need to cause disruption to them while the assay test is carried out.

For bacteria, the results show that the technology can determine both the growth rate and lag phase duration, with the data entirely consistent with conventional OD reading and CFU counts. The technique showed scope to assess the effects of substances on microbial growth and to estimate both bacterial loads in samples and potential bacterial effects - apparently much faster and just as reliably as conventional screening methods. Furthermore, unlike conventional optical OD measurement methods, the instrument can be applied to opaque samples like blood, stool or milk.

The technique was also shown to have strong application in parasitology. The low mass and high thermal conductivity of the microcalorimetric vials increase sensitivity to very high levels, thus enabling accurate data to be gathered from single parasitic worms and decreasing the need to sacrifice hosts. The technology was said to be sensitive enough to offer a similar throughput to the traditional microscopic approach, but with a significantly reduced workload due to the elimination of continual microscopic evaluation based on motor activity.

The studies’ lead investigator, Oliver Braissant, described isothermal microcalorimetry as “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”. For example, microcalorimetric data, when combined with other data sets, enables the pinpointing of useful heat production time points; the new approach can thus be utilised for research in the screening of protease inhibitors.

Symcel CEO Christer Wallin said the results “clearly demonstrate that a well plate instrument, combining the throughput of well plate assays with the sensitivity of isothermal calorimetry, has strong applicability to the fields of microbiology, oncology and parasitology”.

“In particular, the technique and our CalScreener technology has shown itself to be a highly accurate and reliable assay that monitors the metabolic activity of cancerous micro tissues,” Wallin continued. “Moreover, it represents a uniquely versatile technology since we are independent of cell morphology and can monitor cells in 2D, 3D as well as in tissue samples, bringing innovation to the life science research market that is in such strong demand to bridge early in vitro data to better predictive in vivo models.”