The Analysis of Microorganisms by Microcalorimetry in the Pharmaceutical Industry

Abstract

Many features of microorganisms make them pre-eminently suitable for study by microcalorimetry. They have thus, in the past, been the basis of fundamental studies in metabolism and cellular physiology. In this review we look at the application of calorimetry to the impact of bacteria and fungi on the pharmaceutical industry both in the exploitation of useful microorganisms and the fight against harmful ones. Obviously they are of great relevance to the pharmaceutical industry as agents of human disease, with more antimicrobial products registered for production than for any other type of human affliction. Microcalorimetry offers the opportunity to study microorganisms in real time and in heterogeneous systems, allowing for more descriptive and representative analysis. Other advantages that microcalorimetry confers over traditional microbiological techniques are reductions in time, better reproducibility and simplicity. Also the manufacture of all pharmaceutical products requires the exclusion of microorganisms to a greater or lesser degree. The enumeration and identification of such contaminants is of great importance for the well-being of patients and to maintain the integrity of the product. New techniques are required to increase the reliability and sensitivity over conventional methods. Finally, as our understanding of biology develops, the sophistication of therapeutic agents available, such as vaccines, cytokines and engineered antibodies, is increasing. Necessarily, prokaryotic and eukaryotic cells, possibly transformed with the appropriate genes, are the producers of such proteins. Microcalorimetry offers a sensitive means of developing the conditions for optimum production of such products in active form since it gives instantaneous information on the physiology of the producer cell.

Preservative Efficacy Screening of Pharmaceutical Formulations Using ATP Bioluminescence

“…These studies also indicate that, for the various organisms tested, except A. niger, and C. albicans, the system sensitivity for direct enumeration is in the region of 100 cells/mL. This is substantially more sensitive than other methods for nonfilterable products (Škof et al, 2004;Vine & Bishop, 2005). Statistical evaluation using t-test for paired data also confirms the preliminary results (Table 4), as we found no significant difference at the significance level a = .05.…”

Quantification of vital adherent Streptococcus sanguinis cells on protein-coated titanium after disinfectant treatment

“…Thus, metabolism and growth of relatively limited numbers of bacteria can be monitored continuously and accurately at any chosen temperature [17][18][19]. In microbiology, microcalorimetry has been used to determine replication rates of bacterial cells [20,21], effects of biocides on microbial activity [22,23], and bacterial coaggregation [24] as well as to identificy bacterial species by the patterns of their heat flow rate curves [25][26][27][28]. Hauser-Gerspach et al [29] showed that IMC allows estimating the rate of bacterial adhesion onto surfaces.…”

Isothermal Microcalorimetry of Tumor Cells: Enhanced Thermogenesis by Metastatic Cells

“…Albeit not so numerous, the applications of ITC have gone beyond binary ligand reactions and also included the study of whole living cells. Thus, microcalorimetry studies have been applied to microorganisms (22)(23)(24) and to cells and tissues slices (25). When studying the interactions of biomolecules in solution the titration relies mainly on multiple injections of the samples, whereas with whole cells, single injections may be the method of choice (26).…”