title: A multiplexed three-dimensional paper-based electrochemical impedance device for simultaneous label-free affinity sensing of total and glycated haemoglobin: The potential of using a specific single-frequency value for analysis.
abstract: A novel three-dimensional paper-based electrochemical impedance device (3D-PEID) is first introduced for measuring multiple diabetes markers. Herein, a simple 3D-PEID composed of a dual screen-printed electrode on wax-patterned paper coupled with a multilayer of magnetic paper was fabricated for label-free electrochemical detection. The results clearly demonstrated in a step-wise manner that the haptoglobin (Hp)-modified and 3-aminophenylboronic acid (APBA)-modified eggshell membranes (ESMs) were highly responsive to a clinically relevant range of total (0.5-20 g dL(-1); r(2) = 0.989) and glycated haemoglobin (HbA1c) (2.3%-14%; r(2) = 0.997) levels with detection limits (S/N = 3) of 0.08 g dL(-1) and 0.21%, respectively. The optimal binding frequencies of total haemoglobin and HbA1c to their specific recognition elements were 5.18 Hz and 9.99 Hz, respectively. The within-run coefficients of variation (CV) were 1.84%, 2.18%, 1.72%, and 2.01%, whereas the run-to-run CVs were 2.11%, 2.41%, 2.08%, and 2.21%, when assaying two levels of haemoglobin and HbA1c, respectively. The CVs for the haemoglobin and HbA1c levels measured on ten independently fabricated paper-based sheets were 1.96% and 2.10%, respectively. These results demonstrated that our proposed system achieved excellent precision for the simultaneous detection of total haemoglobin and HbA1c, with an acceptable reproducibility of fabrication. The long-term stability of the Hp-modified eggshell membrane (ESM) was 98.84% over a shelf-life of 4 weeks, enabling the possibility of storage or long-distance transport to remote regions, particularly in resource-limited settings; however, for the APBA-modified ESM, the stability was 92.35% over a one-week period. Compared with the commercial automated method, the results demonstrated excellent agreement between the techniques (p-value < 0.05), thus permitting the potential application of 3D-PEID for the monitoring of the glycaemic status in diabetic patients.
authors: Graduate Program in Clinical Biochemistry and Molecular Medicine, Faculty of Allied Health Sciences, Chulalongkorn University, Bangkok, 10330, Thailand.
authors: Yuwadee
authors: Y
authors: Boonyasit
authors: Electrochemistry and Optical Spectroscopy Research Unit (EOSRU), Department of Chemistry, Faculty of Science, Chulalongkorn University, Bangkok, 10330, Thailand.
authors: Orawon
authors: O
authors: Chailapakul
authors: Department of Clinical Chemistry, Faculty of Allied Health Sciences, Chulalongkorn University, Bangkok, 10330, Thailand. Electronic address: Wanida.L@chula.ac.th.
authors: Wanida
authors: W
authors: Laiwattanapaisal
mesh_terms: D015415:Biomarkers / Q000097:blood / Q000737:chemistry; D001774:Blood Chemical Analysis / Q000295:instrumentation*; D001897:Boronic Acids / Q000737:chemistry; D003920:Diabetes Mellitus / Q000097:blood; D017097:Electric Impedance; D004566:Electrodes; D004867:Equipment Design; D006442:Glycated Hemoglobin / Q000032:analysis* / Q000737:chemistry; D006801:Humans; D057230:Limit of Detection; D010209:Paper; D013997:Time Factors
chemical_list: D015415:Biomarkers; D001897:Boronic Acids; D006442:Glycated Hemoglobin; C028592:3-aminobenzeneboronic acid
keywords: 3-Aminophenylboronic acid; Eggshell membrane; Glycated haemoglobin; Haptoglobin; Label-free electrochemical detection; Three-dimensional paper-based electrochemical impedance device