NDLI: Continuous monitoring of drug effects on complex biological samples by segmented flow chip calorimetry

Content Provider	Springer Nature Link
Author	Lerchner, J. David, K. A. Unger, F. T. Lemke, K. Förster, T. Mertens, F.
Copyright Year	2016
Abstract	In the presented paper, the capability of segmented flow chip calorimeters for the analysis of time-dependent pharmaceutical effects on differently complex biological systems is demonstrated. Due to the noninvasive nature of calorimetric measurements, the dynamics of metabolic changes in living material can be analyzed more precisely compared to endpoint methods, in particular in case of highly inhomogeneous sample material. In comparison to batch and conventional flow-through calorimeters, the segmented flow technology enables increased throughput and defined cultivation conditions of the investigated material. Samples of 1 mm$^{3}$ of colorectal cancer tissue were treated with 5-Fluorouracil or staurosporine and subsequently analyzed by segmented flow chip calorimetry. The observed dynamics of the drug effects is characterized by defined inflection points in the heat rate curves. All data of the onset time were similar for a given drug. In contrast, the rate of metabolic deactivation of the tissue affected by the treatment was strongly dependent on the biology of the tumor from individual patients. The heat evolution of fibroblast spheroids treated with staurosporine showed a similar dynamics as observed in treated colorectal cancer tissue samples. However, the heat production of synthetic micro-tissues was more uniform than the heat production of the highly inhomogeneous cancer tissue, directly derived from surgical patients. The investigation of the effect of adrenalin and noradrenalin on the metabolism of daphnia demonstrated the excellent real-time capabilities of the used segmented flow chip calorimeter. An increased heat production rate could be measured already few minutes after start of treatment. The small thermal time constant of the calorimeter of only 25 s enabled the detection of drug-caused changes in the motility of the daphnia in a frequency bandwidth of 0.02 Hz.
Starting Page	1307
Ending Page	1317
Page Count	11
File Format	PDF
ISSN	13886150
Journal	Journal of thermal analysis
Volume Number	127
Issue Number	2
e-ISSN	15882926
Language	English
Publisher	Springer Netherlands
Publisher Date	2016-12-27
Publisher Place	Dordrecht
Access Restriction	One Nation One Subscription (ONOS)
Subject Keyword	Segmented flow chip calorimeters Metabolic heat production Colon cancer tissue Fibroblast spheroids Daphnia motility Physical Chemistry Analytical Chemistry Polymer Sciences Inorganic Chemistry Measurement Science and Instrumentation
Content Type	Text
Resource Type	Article
Subject	Physical and Theoretical Chemistry Condensed Matter Physics

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