Calorimetry a New Paradigm in Cell-based Assays

Measuring the metabolic activities in living organisms is a well established science. In 1784, Antoine Laurent Lavoisier and Pierre Simon de Laplace cleverly devised the first calorimetric device, using heat to measure chemical and physical changes. Calorimeters have evolved to become a modern tool for the advancement of science. Large volume single channel calorimeters have found wide spread applications in the industry, mainly in material, chemical and pharmaceutical companies.

old_calorimetry

SymCel is introducing the first calorimeter developed specifically for cell-based assays suitable for both advanced metabolic research as well as drug discovery and development applications.

 

 

 

 

 

Creating Solutions for You

calScreener technology is valid for monitoring changes in biological processes caused by physical, chemical or biological stimuli. Changes in metabolic activity will cause changes in heat dissipated from the cell, tissue or organism.

Depending on the biological process involved different kinetic behaviors are anticipated. The graphs below are idealized examples of the different heat output over time from different cellular processes.
 

graph2

 

Calorimetry technology can be applied to



Drug development

  • Bioavailability – Are your compounds able to affect living cells?
  • Target validation
  • Hit validation; rapid assessment of effect on cells
  • Rapid filtering of hit compounds with in-built toxicity testing
  • Lead selection

Protein Production

  • Identification of High-producing Clones
  • Optimization of Culture Conditions

Toxicology

  • Identify toxicological events at early stage in the discovery process

Basic Research

  • Metabolic monitoring
     
  • Proliferation assays
     
  • Other

calScreener is not limited to these few applications. The application areas are limited only by the imagination of the scientist. We strongly encourage you to discuss with us your label-free cell-assay ideas and requirements.
 

The calScreener Principle

Biological processes caused by physical, chemical or biological stimuli in which metabolic changes are anticipated are all valid for the analysis.

The calPlate containing the individual sealed cups holding the cell culture are placed in a thermostatic chamber set at the target temperature with a precision within thousands of a Kelvin.
The cups rest upon a heat-flux detecting sensor, the thermopile. The sensor is attached to a heat-sink with a large mass compared to the cell-culture cups. All heat produced is transferred to the heat-sink giving rise to a signal in the thermopile sensor proportional to the heat-flow. CalScreener_principle

The measured heat is thus independent of the model system or the process involved. We have a label free, real-time, detection system applicable to a wide range of biological applications

References

Below are some publication examples of biological processes and applications where heat measurements have been conducted using calorimetric equipment, including measurement of basic cellular responses such as cell proliferation, cell death (apoptosis) and cell signaling.

Apoptosis
Apoptotic processes are manifested by a typical heat pattern when DNA is fragmented

Bermudez, J., P. Backman, et al. (1992). “Microcalorimetric evaluation of the effects of methotrexate and 6-thioguanine on sensitive T-lymphoma cells and on a methotrexate-resistant subline.” Cell Biophys. 20(2-3): 111-23.
Wallen-Öhman, M., P. Lönnbro, et al. (1993). “Antibody-induced apoptosis in a human leukemia cell line is energy dependent: thermochemical analysis of cellular metabolism.” Cancer Letters 75(2): 103-9.
Roig, T. and J. Bermudez (1995). “Microcalorimetric evaluation of the effect of combined chemotherapeutic drugs.” Biochim Biophys Acta. 1244(2-3): 283-90.
Bluthnerhassler, C., M. Karnebogen, et al. (1995). “Influence of Malignancy and Cyctostatic Treatment on Microcalorimetric Behavior of Urological Tissue Samples and Cell-Cultures.” Thermochimica Acta 251: 145-154.

Thermogenesis

Böttcher, H. and P. Fürst (1996). “Microcalorimetric and biochemical investigations of thermogenesis and metabolic pathways in human white adipocytes.” Int J Obes Relat Metab Disord. 20(9): 874-81.
Hinz, W., B. Faller, et al. (1999). “Recombinant human uncoupling protein-3 increases thermogenesis in yeast cells.” FEBS Lett. 448(1): 57-61.

Growth

Feng, Y., S. F. Luo, et al. (1997). “Study on the thermosensitivity of a tumor cell by microcalorimetry.” Thermochimica Acta 303(2): 203-207.
Andlid, T., L. Blomberg, et al. (1999). “Characterization of Saccharomyces cerevisiae CBS 7764 isolated from rainbow trout intestine.” Systematic and Applied Microbiology 22(1): 145-155.
Barros, N., S. Feijoo, et al. (2001). “Interpretation of the metabolic enthalpy change, DHmet, calculated for microbial growth reactions in soils.” Journal of Thermal Analysis and Calorimetry 63(2): 577-588.
Dejean, L., O. Bunoust, et al. (2002). “Control of growth yield of yeast on respiratory substrate by mitochondrial content.” Thermochimica Acta 394(1-2): 113-121.