Wireless Thermometry for Real-Time Temperature Recording on Thousand-Cell Level

Objective: A wireless, multichannel system for real-time measurement of the cellular-temperature response to drugs is developed. Methods: The acquisition system applies a high-precision reference resistor and a low real-time measurement current (below or equal to 0.14 mA) to reduce self-heating via the intermittent measurement. Cells of a small volume cell medium are cultured on the surface of the platinum thermal resistor and subsequently measured in the incubator. Results: The resistance resolution of the circuit exhibits 20 mΩ, which corresponds to no more than 0.01 °C. The resistance deviations of each channel are corrected with software compensation. The linearity between the temperature and resistance of the sensors lies above 0.999 in the applied temperature range (30 °C–42 °C). Observations with the scanning electron microscope show that the cells grow well on the sensor surface. The latter is composed of a glass glaze, which is nontoxic for organisms. The cell population temperature measurements under norepinephrine action present an obvious temperature rise, which can be the result of the drug binding to the receptors on cell membrane thus promoting a cationic inflow. Conclusion: The platinum sensor and multichannel acquisition system can be used to determine the temperature changes of cells in their original state. Significance: The wireless, real-time, high-throughput temperature detection method is particularly suitable to evaluate the thermogenic ability of growing cells that interact with other matter or organisms. The proposed method can help to explore thermal changes in cell populations, intercellular connections, and social connections of cells.

[1]  Bruce M. Spiegelman,et al.  Towards a molecular understanding of adaptive thermogenesis , 2000, Nature.

[2]  G. Ronquist,et al.  Dissipation of the calcium gradient in human erythrocytes results in increased heat production. , 1993, Clinica chimica acta; international journal of clinical chemistry.

[3]  Yang Haibo High-precision temperature measurement system based on PT1000 , 2010 .

[4]  Kotaro Oyama,et al.  Microscopic detection of thermogenesis in a single HeLa cell. , 2007, Biophysical journal.

[5]  Thomas Dalsgaard,et al.  Elementary Ca2+signals through endothelial TRPV4 channels regulate vascular function , 2013, BMC Pharmacology and Toxicology.

[6]  Ning Gu,et al.  Micro/Nanoscale Thermometry for Cellular Thermal Sensing. , 2016, Small.

[7]  Heng Huang,et al.  Remote control of ion channels and neurons through magnetic-field heating of nanoparticles. , 2010, Nature nanotechnology.

[8]  Liwei Lin,et al.  Quantum dot nano thermometers reveal heterogeneous local thermogenesis in living cells. , 2011, ACS nano.

[9]  David E. Clapham,et al.  TRPV3 is a calcium-permeable temperature-sensitive cation channel , 2002, Nature.

[10]  M. Benchimol,et al.  Fusion of the Endoplasmic Reticulum and Mitochondrial Outer Membrane in Rats Brown Adipose Tissue: Activation of Thermogenesis by Ca2+ , 2010, PloS one.

[11]  Meng Wang,et al.  Determining intracellular temperature at single-cell level by a novel thermocouple method , 2011, Cell Research.

[12]  A. Malik,et al.  Ca2+ Signaling, TRP Channels, and Endothelial Permeability , 2006, Microcirculation.

[13]  D. Julius,et al.  The capsaicin receptor: a heat-activated ion channel in the pain pathway , 1997, Nature.

[14]  D L Alkon,et al.  Thermal imaging of receptor-activated heat production in single cells. , 1998, Biophysical journal.

[15]  David F. Albertini,et al.  THE APPEARANCE AND STRUCTURE OF INTERCELLULAR CONNECTIONS DURING THE ONTOGENY OF THE RABBIT OVARIAN FOLLICLE WITH PARTICULAR REFERENCE TO GAP JUNCTIONS , 1974, The Journal of cell biology.

[16]  Satoshi Arai,et al.  Mitochondria-targeted fluorescent thermometer monitors intracellular temperature gradient. , 2015, Chemical communications.

[17]  Leopoldo de Meis,et al.  Role of the sarcoplasmic reticulum Ca2+-ATPase on heat production and thermogenesis. , 2001 .

[18]  D. Inlow,et al.  CO2 in large-scale and high-density CHO cell perfusion culture , 2004, Cytotechnology.

[19]  H B Hechtman,et al.  Serotonin, norepinephrine, and histamine mediation of endothelial cell barrier function in vitro , 1986, Journal of cellular physiology.

[20]  Masasuke Yoshida,et al.  ATP synthase — a marvellous rotary engine of the cell , 2001, Nature Reviews Molecular Cell Biology.

[21]  Sung Eun Kim,et al.  Temperature-induced opening of TRPV1 ion channel is stabilized by the pore domain , 2010, Nature Neuroscience.

[22]  Gyun Min Lee,et al.  Effect of low culture temperature on specific productivity, transcription level, and heterogeneity of erythropoietin in Chinese hamster ovary cells. , 2003, Biotechnology and bioengineering.

[23]  V. V. van Hinsbergh,et al.  Norepinephrine and iloprost improve barrier function of human endothelial cell monolayers: role of cAMP. , 1991, The American journal of physiology.

[24]  Balaji Manicassamy,et al.  Influenza A Virus Uses Intercellular Connections To Spread to Neighboring Cells , 2014, Journal of Virology.

[25]  Thomas Ryll,et al.  Effects of temperature shift on cell cycle, apoptosis and nucleotide pools in CHO cell batch cultues , 2004, Cytotechnology.

[26]  Zhu Yu-hong An accurate measurement method for platinum resistance , 2007 .

[27]  Fumihito Arai,et al.  Temperature changes in brown adipocytes detected with a bimaterial microcantilever. , 2014, Biophysical Journal.

[28]  J. Nishimura,et al.  Norepinephrine and GTP-γ-S increase myofilament Ca2+ sensitivity in α-toxin permeabilized arterial smooth muscle , 1988 .

[29]  Takahito Ono,et al.  Pico calorimeter for detection of heat produced in an individual brown fat cell , 2012 .

[30]  P. Blackmore,et al.  Changes in free cytosolic Ca2+ in hepatocytes following alpha 1-adrenergic stimulation. Studies on Quin-2-loaded hepatocytes. , 1983, The Journal of biological chemistry.

[31]  Maiken Nedergaard,et al.  α1-Adrenergic receptors mediate coordinated Ca2+ signaling of cortical astrocytes in awake, behaving mice. , 2013, Cell calcium.