Boronate-Modified Interdigitated Electrode Array for Selective Impedance-Based Sensing of Glycated Hemoglobin.
An impedance-based label-free affinity sensor was developed for the recognition of glycated hemoglobin (HbA1c). Interdigitated gold microelectrode arrays (IDAs) were first modified with a self-assembled monolayer of cysteamine followed by cross-linking with glutaraldehyde and subsequent binding of 3-aminophenylboronic acid (APBA), which selectively binds HbA1c via cis-diol interactions. Impedance sensing was demonstrated to be highly responsive to the clinically relevant HbA1c levels (0.1%-8.36%) with a detection and quantitation limit of 0.024% (3σ/slope) and 0.08% (10σ/slope), respectively. The specificity of the assay was evaluated with nonglycated hemoglobin (HbAo), showing that the impedance response remained unchanged over the concentration range of 10 to 20 g dL-1HbAo. This demonstrated that the sensor system could be used to specifically distinguish HbA1c from HbAo. Moreover, the binding of HbA1c to the APBA-modified electrodes was reversible, providing a reusable sensing interface as well as showing a stable response after 4 weeks (96% of the initial response). When assaying normal (4.10%) and diabetic (8.36%) HbA1c levels (10 assays per day during a three-day period including a regeneration step after each assay), the overall assay reproducibility, expressed as relative standard error of the mean (n = 30), was 1.1%. The performance of the sensor system was also compared with a commercial method (n = 15) using patient-derived blood samples. A good agreement (Bland-Altman bias plot) and correlation (Passing-Bablok regression analysis) was demonstrated between the boronate-based affinity sensor and the standard method.
Graduate Program in Clinical Biochemistry and Molecular Medicine, Faculty of Allied Health Sciences, Chulalongkorn University , Bangkok, 10330, Thailand.|Department of Micro- and Nanotechnology, Technical University of Denmark , Kongens Lyngby, 2800, Denmark.
Yuwadee
Y
Boonyasit
Department of Clinical Chemistry, Faculty of Allied Health Sciences, Chulalongkorn University , Bangkok, 10330, Thailand.
Wanida
W
Laiwattanapaisal
Electrochemistry and Optical Spectroscopy Research Unit (EOSRU), Department of Chemistry, Faculty of Science, Chulalongkorn University , Bangkok, 10330, Thailand.
Orawon
O
Chailapakul
Department of Micro- and Nanotechnology, Technical University of Denmark , Kongens Lyngby, 2800, Denmark.
Jenny
J
Emnéus
Department of Micro- and Nanotechnology, Technical University of Denmark , Kongens Lyngby, 2800, Denmark.|Department of Clinical Chemistry, Faculty of Allied Health Sciences, Chulalongkorn University , Bangkok, 10330, Thailand.
Arto R
AR
Heiskanen
D015374:Biosensing Techniques / Q000295:instrumentation; D001897:Boronic Acids / Q000737:chemistry*; D017097:Electric Impedance; D004566:Electrodes; D006442:Glycated Hemoglobin / Q000032:analysis*; D006046:Gold / Q000737:chemistry; D006801:Humans; D013499:Surface Properties
D001897:Boronic Acids; D006442:Glycated Hemoglobin; D006046:Gold