Highly permselective uric acid detection using kidney cell membrane–functionalized enzymatic biosensors

Insu Kim; Young Im Kim; Sang Won Lee; Hyo Gi Jung; Gyudo Lee; Dae Sung Yoon

doi:10.1016/j.bios.2021.113411

Highly permselective uric acid detection using kidney cell membrane–functionalized enzymatic biosensors

Insu Kim, Young Im Kim, Sang Won Lee, Hyo Gi Jung, Gyudo Lee, Dae Sung Yoon

School of Biomedical Engineering

Research output: Contribution to journal › Article › peer-review

24 Citations (Scopus)

Abstract

Abnormal blood uric acid (UA) levels can lead to its crystallization in the joints, consequently resulting in gout. Accurate detection of UA in the blood is imperative for the early diagnosis of gout. However, electrochemical UA biosensors are vulnerable to antioxidants in the blood, limiting accurate UA detection. To address this issue, we focused on the function of uric acid transporter 1 (URAT1), which is selectively permeable to UA. URAT1 is abundant in the kidney cell membrane (KCM). To apply URAT1 to a sensor, we developed a KCM-coated UA biosensor (called the KCM sensor) that could selectively detect UA through URAT1. The KCM coating in the fabricated KCM sensor was verified via scanning electron microscopy, atomic force microscopy, and confocal microscopy. The KCM sensor enabled the detection of UA in the range of 0–1000 μM, with a limit of detection of 8.5 μM, suggesting that it allows the diagnosis of the early stages of gout. On the other hand, the UA permeability of the KCM sensor was significantly reduced in the presence of a URAT1 inhibitor, implying that URAT1 is a key factor for UA detection. The selectivity of the KCM sensor was demonstrated by measuring the amount for UA in the presence of various antioxidants. Finally, the KCM sensor was capable of measuring UA in human serum and was reproducible with 0.5–1.6% deviation. The UA permeability and selectivity of the KCM sensor were maintained even after 3 weeks of storage.

Original language	English
Article number	113411
Journal	Biosensors and Bioelectronics
Volume	190
DOIs	https://doi.org/10.1016/j.bios.2021.113411
Publication status	Published - 2021 Oct 15

Bibliographical note

Funding Information:
This work was supported by the National Research Foundation of Korea (NRF) Grant funded by the Korean Government ( MSIP ) (No., NRF-2018M3C1B7020722 , NRF-2019R1A2B5B01070617 , and 2020R1A6A3A01096477 ). This work was supported by the Korea Medical Device Development Fund grant funded by the Korea government (the Ministry of Science and ICT ), Project Number: 202012D19 . This study was also supported by the BK21 FOUR (Fostering Outstanding Universities for Research) .

Publisher Copyright:
© 2021 Elsevier B.V.

Keywords

Electrochemical detection
Kidney cell membrane
Permselectivity
Urate transporter 1
Uric acid biosensor
Uric acid oxidase

ASJC Scopus subject areas

Biotechnology
Biophysics
Biomedical Engineering
Electrochemistry

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10.1016/j.bios.2021.113411

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title = "Highly permselective uric acid detection using kidney cell membrane–functionalized enzymatic biosensors",

abstract = "Abnormal blood uric acid (UA) levels can lead to its crystallization in the joints, consequently resulting in gout. Accurate detection of UA in the blood is imperative for the early diagnosis of gout. However, electrochemical UA biosensors are vulnerable to antioxidants in the blood, limiting accurate UA detection. To address this issue, we focused on the function of uric acid transporter 1 (URAT1), which is selectively permeable to UA. URAT1 is abundant in the kidney cell membrane (KCM). To apply URAT1 to a sensor, we developed a KCM-coated UA biosensor (called the KCM sensor) that could selectively detect UA through URAT1. The KCM coating in the fabricated KCM sensor was verified via scanning electron microscopy, atomic force microscopy, and confocal microscopy. The KCM sensor enabled the detection of UA in the range of 0–1000 μM, with a limit of detection of 8.5 μM, suggesting that it allows the diagnosis of the early stages of gout. On the other hand, the UA permeability of the KCM sensor was significantly reduced in the presence of a URAT1 inhibitor, implying that URAT1 is a key factor for UA detection. The selectivity of the KCM sensor was demonstrated by measuring the amount for UA in the presence of various antioxidants. Finally, the KCM sensor was capable of measuring UA in human serum and was reproducible with 0.5–1.6% deviation. The UA permeability and selectivity of the KCM sensor were maintained even after 3 weeks of storage.",

keywords = "Electrochemical detection, Kidney cell membrane, Permselectivity, Urate transporter 1, Uric acid biosensor, Uric acid oxidase",

author = "Insu Kim and Kim, {Young Im} and Lee, {Sang Won} and Jung, {Hyo Gi} and Gyudo Lee and Yoon, {Dae Sung}",

note = "Funding Information: This work was supported by the National Research Foundation of Korea (NRF) Grant funded by the Korean Government ( MSIP ) (No., NRF-2018M3C1B7020722 , NRF-2019R1A2B5B01070617 , and 2020R1A6A3A01096477 ). This work was supported by the Korea Medical Device Development Fund grant funded by the Korea government (the Ministry of Science and ICT ), Project Number: 202012D19 . This study was also supported by the BK21 FOUR (Fostering Outstanding Universities for Research) . Publisher Copyright: {\textcopyright} 2021 Elsevier B.V.",

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doi = "10.1016/j.bios.2021.113411",

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AU - Yoon, Dae Sung

N1 - Funding Information: This work was supported by the National Research Foundation of Korea (NRF) Grant funded by the Korean Government ( MSIP ) (No., NRF-2018M3C1B7020722 , NRF-2019R1A2B5B01070617 , and 2020R1A6A3A01096477 ). This work was supported by the Korea Medical Device Development Fund grant funded by the Korea government (the Ministry of Science and ICT ), Project Number: 202012D19 . This study was also supported by the BK21 FOUR (Fostering Outstanding Universities for Research) . Publisher Copyright: © 2021 Elsevier B.V.

PY - 2021/10/15

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N2 - Abnormal blood uric acid (UA) levels can lead to its crystallization in the joints, consequently resulting in gout. Accurate detection of UA in the blood is imperative for the early diagnosis of gout. However, electrochemical UA biosensors are vulnerable to antioxidants in the blood, limiting accurate UA detection. To address this issue, we focused on the function of uric acid transporter 1 (URAT1), which is selectively permeable to UA. URAT1 is abundant in the kidney cell membrane (KCM). To apply URAT1 to a sensor, we developed a KCM-coated UA biosensor (called the KCM sensor) that could selectively detect UA through URAT1. The KCM coating in the fabricated KCM sensor was verified via scanning electron microscopy, atomic force microscopy, and confocal microscopy. The KCM sensor enabled the detection of UA in the range of 0–1000 μM, with a limit of detection of 8.5 μM, suggesting that it allows the diagnosis of the early stages of gout. On the other hand, the UA permeability of the KCM sensor was significantly reduced in the presence of a URAT1 inhibitor, implying that URAT1 is a key factor for UA detection. The selectivity of the KCM sensor was demonstrated by measuring the amount for UA in the presence of various antioxidants. Finally, the KCM sensor was capable of measuring UA in human serum and was reproducible with 0.5–1.6% deviation. The UA permeability and selectivity of the KCM sensor were maintained even after 3 weeks of storage.

AB - Abnormal blood uric acid (UA) levels can lead to its crystallization in the joints, consequently resulting in gout. Accurate detection of UA in the blood is imperative for the early diagnosis of gout. However, electrochemical UA biosensors are vulnerable to antioxidants in the blood, limiting accurate UA detection. To address this issue, we focused on the function of uric acid transporter 1 (URAT1), which is selectively permeable to UA. URAT1 is abundant in the kidney cell membrane (KCM). To apply URAT1 to a sensor, we developed a KCM-coated UA biosensor (called the KCM sensor) that could selectively detect UA through URAT1. The KCM coating in the fabricated KCM sensor was verified via scanning electron microscopy, atomic force microscopy, and confocal microscopy. The KCM sensor enabled the detection of UA in the range of 0–1000 μM, with a limit of detection of 8.5 μM, suggesting that it allows the diagnosis of the early stages of gout. On the other hand, the UA permeability of the KCM sensor was significantly reduced in the presence of a URAT1 inhibitor, implying that URAT1 is a key factor for UA detection. The selectivity of the KCM sensor was demonstrated by measuring the amount for UA in the presence of various antioxidants. Finally, the KCM sensor was capable of measuring UA in human serum and was reproducible with 0.5–1.6% deviation. The UA permeability and selectivity of the KCM sensor were maintained even after 3 weeks of storage.

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KW - Kidney cell membrane

KW - Permselectivity

KW - Urate transporter 1

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KW - Uric acid oxidase

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ER -

Highly permselective uric acid detection using kidney cell membrane–functionalized enzymatic biosensors

Abstract

Bibliographical note

Keywords

ASJC Scopus subject areas

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