US 12,344,826 B2
Apparatus and methods for in vitro preclinical human trials
Igor R. Efimov, Arlington, VA (US); Yun Qiao, Arlington, VA (US); Chaoyi Kang, Arlington, VA (US); Zhenyu Li, McLean, VA (US); Quan Dong, Fairfax, VA (US); and Baichen Li, Falls Church, VA (US)
Assigned to THE GEORGE WASHINGTON UNIVERSITY, A CONGRESSIONALLY CHARTERED NOT-FOR-PROFIT CORPORATION, Washington, DC (US)
Appl. No. 16/479,297
Filed by THE GEORGE WASHINGTON UNIVERSITY, A CONGRESSIONALLY CHARTERED NOT-FOR-PROFIT CORPORATION, Washington, DC (US)
PCT Filed Jan. 24, 2018, PCT No. PCT/US2018/015052
§ 371(c)(1), (2) Date Jul. 19, 2019,
PCT Pub. No. WO2018/140497, PCT Pub. Date Aug. 2, 2018.
Claims priority of provisional application 62/450,412, filed on Jan. 25, 2017.
Prior Publication US 2019/0376014 A1, Dec. 12, 2019
Int. Cl. C12M 3/06 (2006.01); A01N 1/122 (2025.01); A01N 1/143 (2025.01); A01N 1/16 (2025.01); A01N 1/162 (2025.01); B01L 3/00 (2006.01); C12M 1/00 (2006.01); C12M 1/02 (2006.01); C12M 1/06 (2006.01); C12M 1/34 (2006.01); C12M 1/36 (2006.01); C12N 5/071 (2010.01); C12N 5/077 (2010.01); C12N 9/22 (2006.01); C12N 15/11 (2006.01); G01N 1/36 (2006.01); G01N 33/50 (2006.01)
CPC C12M 23/16 (2013.01) [A01N 1/122 (2025.01); A01N 1/143 (2025.01); A01N 1/16 (2025.01); A01N 1/162 (2025.01); B01L 3/502715 (2013.01); C12M 27/02 (2013.01); C12M 27/16 (2013.01); C12M 29/10 (2013.01); C12M 41/06 (2013.01); C12M 41/18 (2013.01); C12M 41/26 (2013.01); C12M 41/34 (2013.01); C12M 41/48 (2013.01); C12N 5/0657 (2013.01); C12N 5/0697 (2013.01); C12N 9/22 (2013.01); C12N 15/11 (2013.01); G01N 1/36 (2013.01); G01N 33/5014 (2013.01); G01N 33/5088 (2013.01); B01L 2200/025 (2013.01); B01L 2200/10 (2013.01); B01L 2200/143 (2013.01); B01L 2200/185 (2013.01); B01L 2300/027 (2013.01); B01L 2300/0645 (2013.01); B01L 2300/0663 (2013.01); B01L 2300/0819 (2013.01); B01L 2300/10 (2013.01); B01L 2300/12 (2013.01); B01L 2300/18 (2013.01); B01L 2400/0415 (2013.01); B01L 2400/0487 (2013.01); C12N 2310/20 (2017.05); C12N 2800/80 (2013.01); G01N 2001/368 (2013.01)] 14 Claims
 
1. A method for maintaining a cardiac tissue slice in a microfluidic device, the method comprising culturing the cardiac tissue slice in the microfluidic device, wherein the microfluidic device comprises:
(a) a tissue culture chamber that houses the cardiac tissue slice, wherein the tissue culture chamber provides a restricted environment supplied with oxygen and nutrients necessary to maintain a desired phenotype for the cardiac tissue slice;
(b) actuators for minimizing remodeling and dedifferentiation of the cardiac tissue slice and for phenotypic interrogation of the cardiac tissue slice, wherein the actuators comprise an electrical stimulator and a mechanical stimulator;
(c) one or more sensors for measuring one or more physiological parameters of the cardiac tissue slice; and
(d) an electronics module comprising a microcontroller, wherein the electronics module is coupled to the actuators and the one or more sensors by an array of electrodes,
wherein the desired phenotype of the cardiac tissue slice is maintained in the tissue culture chamber by: (1) electrically and mechanically stimulating the cardiac tissue slice with the electrical and mechanical stimulators, respectively, (2) measuring the one or more physiological parameters of the cardiac tissue slice with the one or more sensors, (3) analyzing the phenotype of the cardiac tissue slice, and (4) electrically and mechanically stimulating the cardiac tissue slice with the electrical and mechanical stimulators, respectively, to minimize remodeling and dedifferentiation of the cardiac tissue slice.