title: Continuous immunosensing of myoglobin in human serum as potential companion diagnostics technique.
abstract: To attain early diagnosis of acute myocardial infarction (AMI) with enhanced accuracy, continuous immunosensing has been investigated to measure myoglobin concentration in real-time. To this end, a capture antibody showing rapid reaction kinetics was immobilized on the surface of a surface plasmon resonance sensor. Three problems associated with the continuous sensing of myoglobin in human serum needed to be overcome: non-specific binding of the analyte, aggregation of serum components, and drift of the sensor baseline. Non-specific binding was controlled by pretreating the sample with a detergent mixture consisting of sodium dodecyl sulfate and P20, and adjusting the micelle size and net charge. Aggregation was managed by inactivating certain serum constituents through chelation of heavy metals. Baseline drift perceived in the sensorgram was able to be corrected by compensating for the slope calculated by a linear regression. Under the optimal conditions, the continuous sensor reproducibly traced the varying doses of myoglobin over about 8h with periodic one-point calibration every 3h. The dose-response curve of the sensor was linear with acceptable variations (CVs<4.91% in average) between the detection limit (31.0 ng/mL) and about 2000 ng/mL in the arithmetic scale (R(2)>0.98), covering the clinical concentration range. The immunosensor performance correlated with the Pathfast reference system (R(2)>0.98) and analytical consistency could be maintained for longer than a month if appropriately calibrated. Such immunosensing could be used as a companion diagnostic means along with real-time electrocardiographic measurement, significantly enhancing the sensitivity of AMI diagnosis and thereby enabling treatment at an early stage.
authors.affiliation: Department of Bio-Microsystem Technology, Korea University, 1, 5-ka, Anam-dong, Seongbuk-Gu, Seoul 136-701, Republic of Korea.
authors.forename: Dong-Hyung
authors.initials: DH
authors.lastname: Kim
authors.affiliation: Department of Bio-Microsystem Technology, Korea University, 1, 5-ka, Anam-dong, Seongbuk-Gu, Seoul 136-701, Republic of Korea.
authors.forename: Sung-Min
authors.initials: SM
authors.lastname: Seo
authors.affiliation: Korea Research Institute of Standards and Science, P.O. Box 102, Yuseong, Taejon 305-600, Republic of Korea.
authors.forename: Hyun-Mo
authors.initials: HM
authors.lastname: Cho
authors.affiliation: Medical Center, Korea University, 126-1, 5-ka, Anam-dong, Seongbuk-Gu, Seoul 136-701, Republic of Korea.
authors.forename: Sun-June
authors.initials: SJ
authors.lastname: Hong
authors.affiliation: Medical Center, Korea University, 126-1, 5-ka, Anam-dong, Seongbuk-Gu, Seoul 136-701, Republic of Korea.
authors.forename: Do-Sun
authors.initials: DS
authors.lastname: Lim
authors.affiliation: Department of Bio-Microsystem Technology, Korea University, 1, 5-ka, Anam-dong, Seongbuk-Gu, Seoul 136-701, Republic of Korea; Department of Biotechnology and Bioinformatics, Korea University, 2511 Sejong-ro, Sejong 339-700, Republic of Korea. Electronic address: shpaek@korea.ac.kr.
authors.forename: Se-Hwan
authors.initials: SH
authors.lastname: Paek
mesh_terms: D055910:Antibodies, Immobilized; D015415:Biomarkers / Q000097:blood; D015374:Biosensing Techniques / Q000379:methods* / Q000706:statistics & numerical data; D002138:Calibration; D003902:Detergents; D042241:Early Diagnosis; D006801:Humans; D007118:Immunoassay / Q000379:methods* / Q000706:statistics & numerical data; D057230:Limit of Detection; D016014:Linear Models; D009203:Myocardial Infarction / Q000097:blood / Q000175:diagnosis; D009211:Myoglobin / Q000097:blood* / Q000737:chemistry / Q000276:immunology; D011485:Protein Binding; D015203:Reproducibility of Results; D020349:Surface Plasmon Resonance / Q000379:methods
chemical_list: D055910:Antibodies, Immobilized; D015415:Biomarkers; D003902:Detergents; D009211:Myoglobin
keywords: Anti-serum aggregation; Baseline drift correction; Clinical sample pretreatment; Continuous immunosensor; Immunosensing performances