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Development of a C-reactive protein quantification method based on flow rate measurement of an ink solution pushed out by oxygen gas generated by catalase reaction

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Abstract

A novel determination method for protein biomarkers based on on-chip flow rate measurement was developed using a microchip with organic photodiodes (OPDs). This quantitative method is based on the flow rate measurement of an ink solution pushed out by oxygen gas generated through catalase reaction. The amount of oxygen gas generated in the sample reservoir is dependent on the concentration of the analyte; therefore, the flow rate of the ink solution is also dependent on the concentration of the analyte. The concentration of the analyte can thus be estimated by measurement of the ink solution flow rate. The ink solution flow rate was estimated by measuring the migration time of the ink solution between two points using two OPDs placed below the microchannel. The principle of this method was demonstrated by the measurement of catalase using the microchip. In addition, the developed method was applied to the determination of C-reactive protein (CRP), a biomarker of inflammation, based on a catalase-linked immunosorbent assay (C-LISA). The limit of detection for CRP was 0.20 µg/mL. The method was also applied to the determination of CRP in human serum, and the quantitative values obtained by this method were in excellent agreement with those obtained by the conventional enzyme-linked immunosorbent assay (ELISA) method. The developed method does not require a photodetector with high sensitivity and is thus capable of downsizing; therefore, this will be useful for on-site analyses such as point-of-care testing and field measurements.

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Funding

This work was supported by KAKENHI Grants-in-Aid (Nos. 21H03578 and 22K14709) from the Japan Society for the Promotion Science (JSPS), the Tokyo Metropolitan Government, and Tokyo Metropolitan Government Infectious Disease Research Project.

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Authors and Affiliations

  1. Department of Applied Chemistry, Graduate School of Urban Environmental Sciences, Tokyo Metropolitan University, 1-1 Minami-Osawa, Hachioji, Tokyo, 192-0397, Japan

    Kuizhi Qu, Shoji Yamamoto & Hizuru Nakajima

  2. School of Pharmacy, Tokyo University of Pharmacy and Life Sciences, 1432-1 Horinouchi, Hachioji, Tokyo, 192-0392, Japan

    Kazuhiro Morioka, Konoka Nakamura & Atsushi Shoji

  3. Mebius Advanced Technology Ltd., 3-31-6-105 Nishiogi-Kita, Suginami-Ku, Tokyo, 167-0042, Japan

    Akihide Hemmi

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  1. Kuizhi Qu
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Contributions

KQ: Validation, investigation, data curation, visualization.

KM: Conceptualization, methodology, investigation, data curation, writing (original draft), visualization, project administration, funding acquisition.

KN: Validation, investigation, visualization.

SY: Writing—review and editing.

AH: Resources, supervision.

AS: Writing—review and editing.

HN: Conceptualization, writing (review and editing), project administration, funding acquisition.

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Correspondence to Kazuhiro Morioka or Hizuru Nakajima.

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Qu, K., Morioka, K., Nakamura, K. et al. Development of a C-reactive protein quantification method based on flow rate measurement of an ink solution pushed out by oxygen gas generated by catalase reaction. Microchim Acta 191, 24 (2024). https://doi.org/10.1007/s00604-023-06108-z

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