US 12,415,058 B2
Interpenetrating microstructures for nanochannel-based sampling and/or cargo delivery
Daniel Gallego-Perez, Columbus, OH (US); Natalia Higuita-Castro, Columbus, OH (US); Lingqian Chang, Evanston, IL (US); and Chandan Sen, Upper Arlington, OH (US)
Assigned to Ohio State Innovation Foundation, Columbus, OH (US)
Filed by Ohio State Innovation Foundation, Columbus, OH (US)
Filed on Jan. 18, 2022, as Appl. No. 17/548,011.
Application 17/548,011 is a continuation in part of application No. 16/471,907, granted, now 11,235,132, previously published as PCT/US2017/067630, filed on Dec. 20, 2017.
Claims priority of provisional application 62/438,256, filed on Dec. 22, 2016.
Prior Publication US 2022/0134073 A1, May 5, 2022
Int. Cl. A61M 37/00 (2006.01); A61B 10/00 (2006.01); G03F 7/00 (2006.01)
CPC A61M 37/0015 (2013.01) [A61B 10/0045 (2013.01); G03F 7/0035 (2013.01); A61B 2010/008 (2013.01); A61M 2037/0023 (2013.01); A61M 2037/003 (2013.01); A61M 2037/0038 (2013.01); A61M 2037/0053 (2013.01); A61M 2037/0061 (2013.01)] 21 Claims
OG exemplary drawing
 
1. A method for obtaining a sample from cells within a tissue, the method comprising:
a) providing a microstructure array that comprises:
a planar substrate having a top surface and a bottom surface;
a reservoir in fluid communication with the top surface of the planar substrate; and
a plurality of microstructures projecting from the bottom surface of the planar substrate, each of the plurality of microstructures comprising:
a solid body portion tapering from a base to a distal tip positioned at a height from the bottom surface of the planar substrate, thereby defining a microstructure surface;
a first sampling channel or slit extending from the top surface of the planar substrate to a first channel opening or slit within the microstructure surface, thereby fluidly connecting the reservoir to the first channel opening or slit; and
a second sampling channel or slit extending from the top surface of the planar substrate to a second channel opening or slit within the microstructure surface, thereby fluidly connecting the reservoir to the second channel opening or slit; and
a first electrode in electrical contact with the reservoir and a second electrode configured to electrically contact a tissue positioned against the bottom surface of the planar substrate,
wherein the solid body portion of each of the plurality of microstructures is formed from silicon using photolithography and etching,
wherein the first sampling channel or slit and second sampling channel or slit have an inner diameter of 1 to 999 nm,
wherein the first channel opening or slit of each of the plurality of microstructures is positioned within a first plane parallel to the planar substrate, wherein the second channel opening or slit of each of the plurality of microstructures is positioned within a second plane parallel to the planar substrate, and wherein the first plane is distally spaced apart from the second plane,
wherein the first plane is distally spaced apart from the second plane by a distance of from 20% to 60% of the height from the bottom surface of the planar substrate, and
wherein the first channel opening or slit is positioned at the distal tip of each of the plurality of microstructures;
b) applying the microstructure array to the tissue, wherein the bottom surface of the planar substrate is positioned against the tissue and the plurality of microstructures extend into the tissue; and
c) sampling a substance from the cells within a tissue through the first sampling channel and the second sampling channel of each of the plurality of microstructures to the reservoir by applying an electric field through the first electrode and second electrode.