US 12,461,102 B2
Pristine graphene based biosensor for biomarker detection and related core particles, materials compositions methods and systems
Paul W. Dempsey, Los Angeles, CA (US); Spencer Hantula, Long Beach, CA (US); Cristina-Mihaela Sandu Aparicio, Laguna Hills, CA (US); Stefan H. Bossmann, Kansas City, MO (US); Christopher M. Sorensen, Manhattan, KS (US); Obdulia Covarrubias-Zambrano, Lenexa, KS (US); and Jose Covarrubias, Manhattan, KS (US)
Assigned to HAWKEYE BIO, LIMITED, Dublin (IE); THE UNIVERSITY OF KANSAS, Lawrence, KS (US); and KANSAS STATE UNIVERSITY RESEARCH FOUNDATION, Manhattan, KS (US)
Filed by HAWKEYE BIO, LIMITED, Dublin (IE); THE UNIVERSITY OF KANSAS, Lawrence, KS (US); and KANSAS STATE UNIVERSITY RESEARCH FOUNDATION, Manhattan, KS (US)
Filed on Oct. 31, 2022, as Appl. No. 18/051,422.
Application 18/051,422 is a continuation of application No. PCT/US2021/065573, filed on Dec. 29, 2021.
Claims priority of provisional application 63/131,972, filed on Dec. 30, 2020.
Prior Publication US 2023/0258640 A1, Aug. 17, 2023
Int. Cl. G01N 33/573 (2006.01); G01N 33/533 (2006.01); G01N 33/542 (2006.01); G01N 33/543 (2006.01); G01N 33/551 (2006.01)
CPC G01N 33/573 (2013.01) [G01N 33/533 (2013.01); G01N 33/542 (2013.01); G01N 33/54346 (2013.01); G01N 33/551 (2013.01)] 30 Claims
 
1. A graphene biosensor configured to detect a target biomarker, the graphene biosensor comprising:
a graphene core particle and a detectable moiety capable of emitting a fluorescent signal, the detectable moiety is covalently bonded to the graphene core particle through a peptide linkage comprising a recognition sequence specific for the target biomarker,
wherein the graphene core particle comprises
at least two pristine graphene nanosheets having a pristine graphene nanosheet surface stacked over one another to form a pristine graphene aggregate, and
a coating layer covering at least 50% of a pristine graphene nanosheet surface, said coating layer comprising an organic and/or inorganic compound,
wherein the organic and/or inorganic compound has a solubility in water of at least 10 grams per liter H2O at 25 degrees C. and is able to be covalently linked to, or in water electrostatically stably attached to, pristine graphene,
wherein the organic and/or inorganic compound is attached to a pristine graphene nanosheet to form said coating layer,
wherein the pristine graphene of the at least two pristine graphene nanosheets has a carbon content of at least 99%, an oxygen content of less than 1% and is pure, such that the pristine graphene is free of foreign substances and impurities,
wherein the pristine graphene nanosheet and/or the organic and/or inorganic compound of the coating layer is configured to present a functional group capable of binding a corresponding functional group in an aqueous solution,
wherein, the coating layer and the peptide linkage are configured to set a quenching distance between the graphene nanosheets and the detectable moiety in which the graphene nanosheets quench the fluorescent signal of the detectable moiety,
wherein the peptide linkage is further configured to set, upon recognition by the target biomarker of the recognition sequence, an emitting distance between the graphene nanosheets and the detectable moiety wherein the graphene nanosheets do not quench the fluorescent signal of the detectable moiety, and
wherein the target biomarker specific peptide linkage and the detectable moiety thus form a target specific detectable component configured to emit a detectable fluorescent signal upon modification of the peptide linkage by the target biomarker.