US 12,265,078 B2
Modeling neurological disorders and ataxias with cardiac dysfunction using bioengineered heart tissues
Ronald A. Li, Hong Kong (CN); and Kevin D. Costa, New York, NY (US)
Assigned to NOVOHEART INTERNATIONAL LIMITED, Kowloon (HK)
Appl. No. 17/041,912
Filed by NOVOHEART INTERNATIONAL LIMITED, Kowloon (HK)
PCT Filed Mar. 28, 2019, PCT No. PCT/IB2019/000498
§ 371(c)(1), (2) Date Sep. 25, 2020,
PCT Pub. No. WO2019/186283, PCT Pub. Date Oct. 3, 2019.
Claims priority of provisional application 62/649,468, filed on Mar. 28, 2018.
Prior Publication US 2021/0132043 A1, May 6, 2021
Int. Cl. C12M 3/00 (2006.01); C12N 5/077 (2010.01); G01N 5/00 (2006.01); G01N 33/50 (2006.01)
CPC G01N 33/5044 (2013.01) [C12N 5/0657 (2013.01); G01N 33/5082 (2013.01); G01N 2500/10 (2013.01)] 25 Claims
OG exemplary drawing
 
1. A system for screening a compound for a cardiac effect on cardiomyocytes of a diseased organism or engineered cardiomyocytes comprising:
(a) a screening apparatus comprising:
(i) a biocompatible gel comprising a plurality of cardiomyocytes of a diseased organism or a plurality of engineered cardiomyocytes;
(ii) a biocompatible support apparatus for suspending the biocompatible gel, wherein the biocompatible gel and biocompatible support apparatus form a cardiac tissue strip comprising cardiomyocytes of a diseased organism or engineered cardiomyocytes;
(iii) a detection device for detecting movement of the biocompatible gel; and
(iv) an electrical power source for applying an electrical pacing stimulus to the biocompatible gel; and
(b) a second-stage screening apparatus comprising:
(i) at least one organoid module comprising at least one organoid cartridge, wherein the organoid cartridge comprises a media inlet, a media outlet, and at least one wall compatible with an external detection device, wherein each organoid cartridge comprises a cardiomyocyte or a plurality of cardiomyocytes of a diseased organism or an engineered cardiomyocyte or a plurality of engineered cardiomyocytes, and wherein at least one organoid cartridge comprises cardiomyocytes of a diseased organism or engineered cardiomyocytes; and
(ii) a detection device for observing the monitored biological development of the cardiomyocytes of the diseased organism or the engineered cardiomyocytes in each organoid cartridge.
 
21. A system for screening a compound for a cardiac effect on cardiomyocytes of a diseased organism or engineered cardiomyocytes comprising:
(a) a screening device comprising:
(i) an anisotropic layer of cardiac cells on a microfabricated substrate;
(ii) an electrical power source for stimulating the anisotropic layer of cells at one or more points; and
(iii) a detection device for detecting an electrical signal propagation in the anisotropic layer of cells; and
(b) a second-stage screening apparatus comprising:
(i) at least one organoid module comprising at least one organoid cartridge, wherein the organoid cartridge comprises a media inlet, a media outlet, and at least one wall compatible with an external detection device, wherein each organoid cartridge comprises a cardiomyocyte or a plurality of cardiomyocytes of a diseased organism or an engineered cardiomyocyte or a plurality of engineered cardiomyocytes, and wherein at least one organoid cartridge comprises cardiomyocytes of a diseased organism or engineered cardiomyocytes; and
(ii) a detection device for observing the monitored biological development of the cardiomyocytes of the diseased organism or the engineered cardiomyocytes in each organoid cartridge.