A Nanotechnology-Enhanced SERS Platform Integrated with Isothermal Amplification for Ultrasensitive Detection of Urinary miR-21 in Early Acute Kidney Injury Diagnosis

Liangping Fan; Wenna Liu; Qian Li; Jixue Lu; Fengchi Jiang; Qi Yan; Xiaoyan Liu; Jie Wang

doi:10.1016/j.jpha.2026.101585

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Liangping Fan, Wenna Liu, Qian Li, Jixue Lu, Fengchi Jiang, Qi Yan, Xiaoyan Liu, Jie Wang. A Nanotechnology-Enhanced SERS Platform Integrated with Isothermal Amplification for Ultrasensitive Detection of Urinary miR-21 in Early Acute Kidney Injury Diagnosis[J]. Journal of Pharmaceutical Analysis. doi: 10.1016/j.jpha.2026.101585

Citation:

Liangping Fan, Wenna Liu, Qian Li, Jixue Lu, Fengchi Jiang, Qi Yan, Xiaoyan Liu, Jie Wang. A Nanotechnology-Enhanced SERS Platform Integrated with Isothermal Amplification for Ultrasensitive Detection of Urinary miR-21 in Early Acute Kidney Injury Diagnosis[J]. Journal of Pharmaceutical Analysis. doi: 10.1016/j.jpha.2026.101585

Citation:

Liangping Fan, Wenna Liu, Qian Li, Jixue Lu, Fengchi Jiang, Qi Yan, Xiaoyan Liu, Jie Wang. A Nanotechnology-Enhanced SERS Platform Integrated with Isothermal Amplification for Ultrasensitive Detection of Urinary miR-21 in Early Acute Kidney Injury Diagnosis[J]. Journal of Pharmaceutical Analysis. doi: 10.1016/j.jpha.2026.101585

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A Nanotechnology-Enhanced SERS Platform Integrated with Isothermal Amplification for Ultrasensitive Detection of Urinary miR-21 in Early Acute Kidney Injury Diagnosis

doi: 10.1016/j.jpha.2026.101585

Liangping Fan^a,
Wenna Liu^a,
Qian Li^a,
Jixue Lu^a,
Fengchi Jiang^a,
Qi Yan^{b
,
,},
Xiaoyan Liu^{a
,
,},
Jie Wang^{a,c
,
,}

a. State Key Laboratory of Macromolecular Drugs and Large-scale Preparation, Hefei Center; School of Pharmacy, Anhui Medical University, Hefei, 230032, China;
b. Department of Clinical Laboratory, the Second Affiliated Hospital of Anhui Medical University, Hefei, 2306012, China;
c. Department of Emergency Surgery, the Second Affiliated Hospital of Anhui Medical University, Hefei, 2306012, China

Funds:

This work was financially supported by the national natural Science Foundation of China (Grant No.: 32401112), the natural Science Foundation of Anhui Province (Grant Nos.: 2408085QH242 and 2308085QH303), the Research fund of Anhui Translational Medicine Research Institute (Grant No.: 2023zhyx-C10), and Doctoral Research Start-up Funds for Introduced Talents of Anhui Medical University (Grant No.: 0601095201).

Received Date: Jul. 21, 2025
Accepted Date: Feb. 09, 2026
Rev Recd Date: Feb. 07, 2026
Available Online: Feb. 10, 2026

Abstract

Abstract

Acute kidney injury (AKI) remains a critical clinical condition with high morbidity and mortality, underscoring the urgent need for early and accurate diagnostic tools. Traditional biomarkers such as serum creatinine (Cer) and blood urea nitrogen (BUN) suffer from delayed response and lack of specificity, limiting their utility in early-stage AKI detection. This study presents an innovative nanotechnology-enabled platform combining isothermal nucleic acid amplification with surface-enhanced Raman scattering (SERS) for the direct and ultrasensitive detection of urinary microRNA-21 (miR-21), a promising early biomarker for AKI. The platform leverages a cascade signal amplification strategy: (1) a polymerase/endonuclease-mediated isothermal amplification system for target recognition and primer generation, (2) a hybridization chain reaction (HCR) to self-assemble DNA nanostructures conjugated with gold nanostars core with silver shell and 4-aminothiophenol (AuNS/Ag@4-ATP) SERS nanoprobes, and (3) a polyadenine-functionalized SERS substrate for robust signal capture. This integrated approach achieves a remarkable detection limit of 8.4 femtomolar (fM), surpassing conventional methods like quantitative reverse transcription polymerase chain reaction (qRT-PCR) in sensitivity while eliminating the need for RNA extraction or thermocycling. Clinical validation using patient urine samples demonstrated the platform’s ability to detect miR-21 elevations 24–48 h earlier than traditional biomarkers, with exceptional specificity and reproducibility (relative standard deviation (RSD) < 5.7%). The modular design and direct urine compatibility highlight its potential for point-of-care applications, offering a rapid (<2 h) and equipment-minimized solution for early AKI diagnosis. This work not only advances AKI biomarker detection but also provides an adaptable framework for other disease-related nucleic acid analyses, bridging nanotechnology with clinical diagnostics.
- Isothermal amplification,
- Acute kidney injury,
- Early diagnosis,
- Surface-enhanced Raman scattering,
- miR-21

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References(39)

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