US 12,465,912 B2
Systems and methods for controlled membrane disruption
Yi-Ping Ho, Ma On Shan (CN); Michael Kenneth Chan, Kowloon Tong (CN); Ming Ming Marianne Lee, Kowloon (CN); Chung Hong Nathaniel Wong, Quarry Bay (CN); and MD Habibur Rahman, Hung Hom (CN)
Assigned to The Chinese University of Hong Kong, Shatin (CN)
Appl. No. 17/602,728
Filed by The Chinese University of Hong Kong, Shatin (CN)
PCT Filed Apr. 10, 2020, PCT No. PCT/CN2020/084117
§ 371(c)(1), (2) Date Oct. 8, 2021,
PCT Pub. No. WO2020/207456, PCT Pub. Date Oct. 15, 2020.
Claims priority of provisional application 62/832,638, filed on Apr. 11, 2019.
Prior Publication US 2022/0168739 A1, Jun. 2, 2022
Int. Cl. B01L 3/00 (2006.01)
CPC B01L 3/502746 (2013.01) [B01L 3/50273 (2013.01); B01L 2200/12 (2013.01); B01L 2200/16 (2013.01); B01L 2300/0663 (2013.01); B01L 2300/0867 (2013.01); B01L 2300/0883 (2013.01); B01L 2400/0478 (2013.01)] 22 Claims
OG exemplary drawing
 
1. A microfluidic device for delivering a payload into a cell, the device comprising:
a microfluidic chip of a generally planar shape and having a plurality of channels and defined therein and which includes:
a first input port configured to receive cells suspended in a first fluid solution;
a first channel of the plurality, the first channel extending along a first axis;
a second input port configured to receive a payload suspended in a second fluid solution;
a second channel of the plurality of channels, the second channel extending along a second axis transverse to the first axis;
a third channel of the plurality of channels, the third channel extending along the first axis;
a fourth channel of the plurality, the fourth channel extending along the second axis;
a cross-junction, at which the first channel, the second channel, the third channel and the fourth channel intersect at a central intersection along a center of the cross-junction,
wherein the first input port is fluidly coupled to the first channel and the first channel extends between the first input port and the intersection such that a flow of the first fluid solution from the first input port flows through the first channel into the central intersection;
wherein the second input port is fluidly coupled to the third channel and the third channel extends between the second input port and the intersection such that a flow of the second fluid solution from the second input port flows through the third channel into the central intersection;
wherein the first and third channels extend from opposite directions toward the intersection such that, when the first and second fluid solutions are introduced into the first and second input ports, the flows of the first and second fluid solutions combine in the cross-junction and form a stagnation point in the central intersection which causes shear to be applied onto cellular membranes of the cells in the first fluid solution so that the cellular membranes stretch and form pores that receive and associate with the payload from the second fluid solution, thereby loading cells with the payload; and
an output port that is fluidly coupled to both the second and fourth channels, wherein the second and fourth channels extend from the intersection in opposite directions along the second axis such that, when the first and second fluid solutions are introduced into the first and second input ports and combine at the central intersection, the loaded cells in the combined first and second solution flow from the central intersection and out the output port.