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Title:
METHOD AND DEVICE FOR EXAMINING MYOCARDIAL TOXICITY AND EVALUATING CARDIOMYOCYTES
Document Type and Number:
WIPO Patent Application WO/2014/098182
Kind Code:
A1
Abstract:
Regarding cardiomyocytes and fibroblasts, it is meaningful to develop a device or system whereby, upon the transmission of pulsation from an adjacent cardiomyocyte or fibroblast, cell potential and cell morphology can be accurately measured on a single cell basis and the toxicity of a drug on cardiomyocytes can be examined on the basis of accurately measured cell potential and cell morphology of a single cell. In the present invention, a mass of cardiomyocytes is disposed on a transparent substrate and the qualities of the cardiomyocytes are evaluated depending on the response of the cardiomyocytes to a forced pulsation stimulus that is applied to the pulsating cardiomyocytes. A mass of cardiomyocytes, said mass being disposed on the transparent substrate, is exposed to a flow of a drug-containing liquid so as to allow the drug to act on cells configuring a network. The level of cardiotoxicity of the drug is evaluated by measuring the fluctuations that are obtained by comparing adjacent pulsating cardiomyocytes in the network.

Inventors:
YASUDA KENJI (JP)
KANEKO TOMOYUKI (JP)
NOMURA FUMIMASA (JP)
Application Number:
PCT/JP2013/084084
Publication Date:
June 26, 2014
Filing Date:
December 19, 2013
Export Citation:
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Assignee:
NAT UNIV CORP TOKYO MED & DENT (JP)
International Classes:
C12M1/34
Foreign References:
JP2010130966A2010-06-17
JPS6349067A1988-03-01
JPS6349066A1988-03-01
JPS6339583A1988-02-20
JP2006094703A2006-04-13
Other References:
KENJI YASUDA ET AL.: "Hito iPS Nado no Kansaibo kara Bunka shita Shinkin Saibo o Mochiita Fuseimyaku Yosokuho no Kaihatsu", SHINDENZU, vol. 31, no. 3, 31 August 2011 (2011-08-31), pages 318 - 324, XP008179459
KANEKO TOMOYUKI ET AL.: "On-chip constructive cell -network study (I): contribution of cardiac fibroblasts to cardiomyocyte beating synchronization and community effect.", JOURNAL OF NANOBIOTECHNOLOGY, vol. 9, 2011, pages 21, XP055258417
NOMURA FUMIMASA ET AL.: "On-chip constructive cell -network study (II): on-chip quasi-in vivo cardiac toxicity assay for ventricular tachycardia/fibrillation measurement using ring-shaped closed circuit microelectrode with lined-up cardiomyocyte cell network.", JOURNAL OF NANOBIOTECHNOLOGY, vol. 9, 2011, pages 39, XP055015088
BRENNAN M; PALANISWAMI M; KAMEN P: "Do existing measures of Poincare plot geometry reflect non-linear features of heart rate variability? Biomedical Engineering", IEEE TRANSACTIONS ON, PROC. IEEE TRANSACTIONS ON BIOMEDICAL ENGINEERING, vol. 48, 2001, pages 1342 - 1347
KANTERS JK; HOLSTEIN-RATHLOU NH; AGNER E: "Lack of evidence for low-dimensional chaos in heart rate variability", JOURNAL OF CARDIOVASCULAR ELECTROPHYSIOLOGY, vol. 5, no. 7, 1994, pages 591 - 601
STORELLA RJ; WOOD HW; MILLS KM ET AL.: "Approximate entropy and point correlation dimension of heart rate variability in healthy subjects", INTEGRATIVE PHYSIOLOGICAL & BEHAVIORAL SCIENCE, vol. 33, no. 4, 1994, pages 315 - 20
PATRICK DAVEY: "How to correct the QT interval for the effects of heart rate in clinical studies", JOURNAL OF PHARMACOLOGICAL AND TOXICOLOGICAL METHODS, vol. 48, 2002, pages 3 - 9
See also references of EP 2937413A4
Attorney, Agent or Firm:
KOBAYASHI Hiroshi et al. (JP)
Kobayashi 浩 (JP)
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