Detection of slight pH changes in skin interstitial fluid (ISF) is crucial yet challenging for studying pathological processes and understanding personal health conditions. In this work, we construct an i-motif DNA based fluorescent ratiometric microneedle sensing patch (IFR-pH MN patch) strategy that enables minimally invasive, high-resolution, and sensitive transdermal monitoring of small pH variations in ISF. The IFR-pH MN patch with advanced integration of both ISF sampling and pH sensing was fabricated from the cross-linking of gelatin methacryloyl and methacrylated hyaluronic acid, wrapping with pH-sensitive hairpin-containing i-motif DNA based fluorescent ratiometric probes in the matrix. Because it is mechanically robust for skin penetration and has high swelling ability, the IFR-pH MN patch could be quickly extracted as sufficient liquid from agarose gel (∼56.4 μL in 10 min). Benefiting from conformation changes of the hairpin-containing i-motif DNA under pH variation and ratiometric fluorescence signal readout, the IFR-pH MN patch could quantitate pH over a small range between pH 6.2 and 6.9 with an accuracy of 0.2 pH units in the mimic skin model. Furthermore, in vivo testing on wound and tumor mouse models indicated the ability of the biocompatible IFR-pH MN patch to penetrate the skin for obtaining transdermal pH values, demonstrating the potential applications in monitoring and intervention of pathological states.

中文翻译：

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基于 I-Motif DNA 的荧光比率微针传感贴片，用于对间质液中微小的 pH 值变化做出灵敏响应


检测皮肤间质液 （ISF） 中轻微的 pH 值变化对于研究病理过程和了解个人健康状况至关重要，但也具有挑战性。在这项工作中，我们构建了一种基于 i-motif DNA 的荧光比率微针传感贴剂 （IFR-pH MN 贴剂） 策略，该策略能够对 ISF 中的微小 pH 变化进行微创、高分辨率和灵敏的透皮监测。IFR-pH MN 贴片采用明胶甲基丙烯酰和甲基丙烯酸酯化透明质酸的交联制成，具有 ISF 采样和 pH 传感的高级集成，并在基质中包裹基于 pH 敏感的含发夹的 i-motif DNA 荧光比率探针。由于它在机械上对皮肤渗透具有很高的溶胀能力，因此可以从琼脂糖凝胶中快速提取 IFR-pH MN 贴剂作为足够的液体（10 分钟内 ∼56.4 μL）。得益于含发夹的 i-motif DNA 在 pH 变化和比率荧光信号读数下的构象变化，IFR-pH MN 贴片可以在 pH 6.2 和 6.9 之间的小范围内定量 pH 值，在模拟皮肤模型中的准确度为 0.2 pH 单位。此外，对伤口和肿瘤小鼠模型的体内测试表明，生物相容性 IFR-pH MN 贴剂能够穿透皮肤以获得透皮 pH 值，证明了在监测和干预病理状态方面的潜在应用。