US 12,282,013 B2
Ex vivo methods of screening for, and characterizing, cardiac therapeutics using preloaded cardiac tissues
Ronald A. Li, Hong Kong (CN); and Kevin D. Costa, New York, NY (US)
Assigned to NOVOHEART INTERNATIONAL LIMITED, Kowloon (HK)
Appl. No. 17/254,264
Filed by NOVOHEART INTERNATIONAL LIMITED, Kowloon (HK)
PCT Filed Jun. 18, 2019, PCT No. PCT/IB2019/055118
§ 371(c)(1), (2) Date Dec. 19, 2020,
PCT Pub. No. WO2019/044044, PCT Pub. Date Dec. 26, 2019.
Claims priority of provisional application 62/687,706, filed on Jun. 20, 2018.
Prior Publication US 2021/0263010 A1, Aug. 26, 2021
Int. Cl. B01L 7/00 (2006.01); B01F 33/302 (2022.01); B01F 33/3033 (2022.01); C12Q 1/6848 (2018.01); C12Q 1/686 (2018.01); G01N 33/483 (2006.01)
CPC G01N 33/4833 (2013.01) 22 Claims
OG exemplary drawing
 
1. A method for assaying a response of a cardiac organoid to a compound comprising:
(a) preloading a cardiac organoid in at least one organoid module by adjusting a hydrostatic pressure inside an organoid chamber to induce a change in stroke work of between 1-50% normalized to an untreated baseline to expand the cardiac organoid prior to administering a compound, wherein the cardiac organoid is housed in at least one organoid module, each organoid module comprising:
(i) a media inlet, a media outlet, and at least one wall compatible with an external detection device, wherein the cardiac organoid comprises at least one human cell, wherein the one human cell is a human embryonic stem cell, a human adult stem cell, a human induced pluripotent stem cell, a cell derived from a human tissue, or a progenitor cell of a human tissue, and wherein the cardiac organoid is in fluid communication with a fluid pump or a fluid reservoir comprising an adjustable volume of fluid, wherein the fluid pump or fluid reservoir modulates the pressure within the organoid;
(ii) a mirror arrangement for simultaneous monitoring of any biological development of the cardiac organoid in each of at least two organoid chambers; and
(iii) a detection device for observing the monitored biological development of the cardiac organoid in each of at least two organoid chambers;
(b) administering the compound to the cardiac organoid; and
(c) detecting a response of the cardiac organoid to the compound.