US 12,377,413 B2
Blood brain barrier-on-a-chip
Young-Sook Son, Seoul (KR); Su-Min Kim, Seoul (KR); Noo Li Jeon, Seoul (KR); Somin Lee, Seoul (KR); and Minhwan Chung, New Haven, CT (US)
Assigned to UNIVERSITY-INDUSTRY COOPERATION GROUP OF KYUNG HEE UNIVERSITY, Yongin-si (KR); and SEOUL NATIONAL UNIVERSITY R&DB FOUNDATION, Seoul (KR)
Filed by UNIVERSITY-INDUSTRY COOPERATION GROUP OF KYUNG HEE UNIVERSITY, Yongin-si (KR); and SEOUL NATIONAL UNIVERSITY R&DB FOUNDATION, Seoul (KR)
Filed on Mar. 30, 2021, as Appl. No. 17/217,037.
Claims priority of application No. 10-2021-0036821 (KR), filed on Mar. 22, 2021.
Prior Publication US 2022/0297117 A1, Sep. 22, 2022
Int. Cl. B01L 3/00 (2006.01); C12M 1/42 (2006.01); C12M 3/00 (2006.01); C12M 3/06 (2006.01); G01N 33/483 (2006.01)
CPC B01L 3/5027 (2013.01) [C12M 21/08 (2013.01); C12M 23/16 (2013.01); C12M 35/08 (2013.01); G01N 33/4833 (2013.01); B01L 2200/027 (2013.01); B01L 2300/0861 (2013.01); G01N 2500/02 (2013.01)] 8 Claims
OG exemplary drawing
 
1. An in vitro blood-brain barrier (BBB)-on-a chip comprising:
a blood-vessel formation channel (C) having a blood-vessel formation channel inlet at one end thereof and a blood-vessel formation channel outlet at the other end thereof;
a pair of first culture liquid sinks disposed on one side of the blood-vessel formation channel (C) and connected to each other via a sink channel (L1), each first culture liquid sink having a predefined space;
a pair of second culture liquid sinks disposed on the other side of the blood-vessel formation channel (C) and connected to each other via a source channel (R1), each second culture liquid sink having each predefined space;
a first culture channel (LO) contacting the sink channel (L1) and having a first culture channel inlet at one end thereof and a first culture channel outlet at the other end thereof; and
a second culture channel (RO) contacting the source channel (R1) and having a second culture channel inlet at one end thereof and a second culture channel outlet at the other end thereof,
wherein at a boundary formed (i) between the first culture channel (LO) and the sink channel (L1), (ii) between the sink channel (L1) and the blood-vessel formation channel (C), (iii) between the blood-vessel formation channel (C) and the source channel (R1), and (iv) between the source channel (R1) and the second culture channel (RO), a plurality of microstructures are formed to define a gap therebetween in which biochemical substances received in each of the blood-vessel formation channel (C), the first culture channel (LO), the second culture channel (RO), the sink channel (L1) and the source channel (R1) react with each other,
wherein the blood-vessel formation channel (C) is consisting essentially of human astrocytes (hACs) and fibrin gel, the sink channel (L1) is consisting essentially of a mixture of endothelial cell growth medium-2 (EGM-2 medium and adipogenic maintenance (AM) medium, a sink channel wall on a side of the blood-vessel formation channel (C) is consisting essentially of human brain microvascular endothelial cells (hBMEC) and human bone marrow-derived mesenchymal stem cells (hBM-MSC), and the second culture channel (RO) is consisting essentially of human lung fibroblasts (hLFs) and fibrinogen.