US 12,352,719 B2
Somatic cell-based electrical biosensor
Craig W. Nies, Greenville, SC (US); and Hari Kishan Rao Abbaraju, Simpsonville, SC (US)
Assigned to KYCERA AVX Components Corporation, Fountain Inn, SC (US)
Filed by AVX Corporation, Fountain Inn, SC (US)
Filed on Sep. 18, 2020, as Appl. No. 17/024,811.
Claims priority of provisional application 62/903,163, filed on Sep. 20, 2019.
Prior Publication US 2021/0088468 A1, Mar. 25, 2021
Int. Cl. G01N 27/327 (2006.01); C01B 32/158 (2017.01); C01B 32/182 (2017.01); C01G 7/00 (2006.01); G01N 27/30 (2006.01)
CPC G01N 27/327 (2013.01) [C01B 32/158 (2017.08); C01B 32/182 (2017.08); C01G 7/00 (2013.01); G01N 27/305 (2013.01)] 10 Claims
OG exemplary drawing
 
1. A biosensor for detecting transepithelial/transendothelial electrical resistance comprising:
at least one substrate;
an adhesion layer that overlies the at least one substrate, wherein the adhesion layer includes tantalum, chromium, tantalum nitride, tungsten-titanium, titanium, titanium nitride, or a combination thereof;
a working electrode that overlies the adhesion layer and is formed on at least a portion of the at least one substrate, the working electrode comprising a biologically inert material, wherein the biologically inert material includes gold, graphene, carbon nanotubes, or a combination thereof;
a reference electrode that overlies the adhesion layer and is formed on the at least one substrate; and
a case, wherein the case defines side walls, a lower wall, and a channel, wherein the channel has a volume of about 150 microliters or less and contacts the working electrode, further wherein the channel extends between at least one inlet and at least one outlet, the at least one inlet having a tapered and/or conical shape and the at least one outlet having a tapered and/or conical shape, further wherein the at least one inlet and the at least one outlet have an innermost part and an outermost part, the outermost part of the at least one inlet and the at least one outlet having a larger diameter than the innermost part of the at least one inlet and the at least one outlet;
wherein the adhesion layer is positioned between the at least one substrate and the working electrode and/or the reference electrode;
wherein spino-cerebral endothelial cells are immobilized with at least one linking agent, wherein the at least one linking agent comprises a thiol, a pyrene, a diazonium, an azide, a sol-gel, or a combination thereof, and further wherein the at least one linking agent continuously covers a portion of a top surface of the working electrode, a side surface of the working electrode, and a portion of a top surface of the at least one substrate;
further wherein at least the portion of the working electrode wherein the spino-cerebral endothelial cells are immobilized is transparent having a percent transmittance of at least 80% but no more than about 99.9%; and
wherein the biosensor is configured to detect a first resistance measurement and a second resistance measurement, wherein the spino-cerebral endothelial cells are immobilized on the portion of the top surface of the working electrode during both the first resistance measurement and the second resistance measurement.