title: Bioelectrocatalytic detection of glycated hemoglobin (HbA1c) based on the competitive binding of target and signaling glycoproteins to a boronate-modified surface.
abstract: We developed an electrochemical glycated hemoglobin (HbA(1c)) biosensor for diagnosing diabetes in whole human blood based on the competitive binding reaction of glycated proteins. Until now, no studies have reported a simple and accurate electrochemical biosensor for the quantification of HbA(1c) in whole blood. This is because it is very difficult to correctly distinguish HbA(1c) from large amounts of hemoglobin and other components in whole blood. To detect glycated hemoglobin, we used electrodes modified with boronic acid, which forms a covalent bond between its diol group and the cis-diol group of the carbohydrate moiety of glycated proteins. For accurate HbA(1c) biosensing, we first removed blood components (except for hemoglobin) such as glycated proteins and blood glucose as they interfere with the boronate-based HbA(1c) competition analysis by reacting with the boronate-modified surface via a cis-diol interaction. After hemoglobin separation, target HbA(1c) and GOx at a predetermined concentration were reacted through a competition onto the boronate-modified electrode, allowing HbA(1c) to be detected linearly within a range of 4.5-15% of the separated hemoglobin sample (HbA(1c)/total hemoglobin). This range covers the required clinical reference range of diabetes mellitus. Hence, the proposed method can be used for measuring %HbA(1c) in whole human blood, and can also be applied to measuring the concentration of various glycated proteins that contain peripheral sugar groups.
authors.affiliation: Medical Diagnostics Team, Materials & Components Laboratory, LG Electronics Advanced Research Institute, Seoul 137724, Republic of Korea.
authors.forename: Seung Yeon
authors.initials: SY
authors.lastname: Song
authors.affiliation: Department of Molecular Science & Technology, Ajou University, Suwon 443749, Republic of Korea.
authors.forename: Yong Duk
authors.initials: YD
authors.lastname: Han
authors.affiliation: Department of Molecular Science & Technology, Ajou University, Suwon 443749, Republic of Korea.
authors.forename: Yoo Min
authors.initials: YM
authors.lastname: Park
authors.affiliation: Department of Molecular Science & Technology, Ajou University, Suwon 443749, Republic of Korea.
authors.forename: Chi Yong
authors.initials: CY
authors.lastname: Jeong
authors.affiliation: Medical Diagnostics Team, Materials & Components Laboratory, LG Electronics Advanced Research Institute, Seoul 137724, Republic of Korea.
authors.forename: Yong Ju
authors.initials: YJ
authors.lastname: Yang
authors.affiliation: Medical Diagnostics Team, Materials & Components Laboratory, LG Electronics Advanced Research Institute, Seoul 137724, Republic of Korea.
authors.forename: Moo Sub
authors.initials: MS
authors.lastname: Kim
authors.affiliation: Medical Diagnostics Team, Materials & Components Laboratory, LG Electronics Advanced Research Institute, Seoul 137724, Republic of Korea.
authors.forename: Yunhee
authors.initials: Y
authors.lastname: Ku
authors.affiliation: Department of Molecular Science & Technology, Ajou University, Suwon 443749, Republic of Korea. Electronic address: hcyoon@ajou.ac.kr.
authors.forename: Hyun C
authors.initials: HC
authors.lastname: Yoon
mesh_terms: D001667:Binding, Competitive; D015374:Biosensing Techniques / Q000379:methods*; D001897:Boronic Acids; D002241:Carbohydrates / Q000097:blood; D011232:Chemical Precipitation; D055664:Electrochemical Techniques; D004800:Enzymes, Immobilized; D005949:Glucose Oxidase; D006442:Glycated Hemoglobin / Q000032:analysis*; D006023:Glycoproteins / Q000097:blood / Q000737:chemistry; D006046:Gold; D006461:Hemolysis; D006801:Humans; D013053:Spectrophotometry; D013499:Surface Properties; D015032:Zinc
chemical_list: D001897:Boronic Acids; D002241:Carbohydrates; D004800:Enzymes, Immobilized; D005949:Glucose Oxidase; D006442:Glycated Hemoglobin; D006023:Glycoproteins; D006046:Gold; D015032:Zinc; C517652:hemoglobin A1c protein, human