Translational Medicine Laboratory, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325035, China.
Department of Burns and Plastic Surgery, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, 210008, China; State Key Laboratory of Bioelectronics, School of Biological Science and Medical Engineering, Southeast University, Nanjing, 210096, China.
Biosens Bioelectron. 2021 Oct 15;190:113404. doi: 10.1016/j.bios.2021.113404. Epub 2021 Jun 5.
The detection of biomarkers in body fluids plays a great role in the diagnosis, treatment, and prognosis of diseases. Here, we present novel aptamer-decorated porous microneedles (MNs) arrays to realize the extraction and detection of biomarkers in skin interstitial fluid (ISF) in situ. The porous MNs arrays are fabricated by replicating the negative molds comprising glass microspheres with a UV-curable ethoxylated trimethylolpropane triacrylate (ETPTA). As the MNs arrays combine the superiorities of porous structure and aptamers, their specific surface area increased significantly to 6.694 m/g, thus vast of stable aptamer probes with a concentration of 0.9459 μM could be immobilized. In addition, the MNs arrays could extract skin ISF into their porous structure on the basis of the capillarity principle, and subsequently capture and detect skin ISF biomarkers without sample post-process. Taking advantage of these features, we further demonstrated a highly sensitive and rapid detection of ISF endotoxin in the concentration ranges of 0.0342 EU/mL to 8.2082 EU/mL from rats model injected with endotoxin via tail vein by using such aptamer-decorated porous MNs arrays, with the limit of detection (LOD) of 0.0064 EU/mL. These results indicated that the aptamer-decorated porous MNs arrays possess great potential for non-invasive extraction and detection of biomarkers in clinical applications.
体液中生物标志物的检测在疾病的诊断、治疗和预后中起着重要作用。在这里，我们提出了一种新的适体修饰的多孔微针（MNs）阵列，以实现皮肤间质液（ISF）中生物标志物的原位提取和检测。多孔 MNs 阵列是通过复制包含玻璃微球的负模来制造的，这些负模使用了可紫外光固化的乙氧基化三羟甲基丙烷三丙烯酸酯（ETPTA）。由于 MNs 阵列结合了多孔结构和适体的优势，其比表面积显著增加到 6.694 m/g，因此可以固定大量浓度为 0.9459 μM 的稳定适体探针。此外，MNs 阵列可以基于毛细作用原理将皮肤 ISF 提取到其多孔结构中，然后无需样品后处理即可捕获和检测皮肤 ISF 生物标志物。利用这些特点，我们进一步通过使用这种适体修饰的多孔 MNs 阵列，从通过尾静脉注射内毒素的大鼠模型中，以 0.0342 EU/mL 至 8.2082 EU/mL 的浓度范围，实现了对内毒素的 ISF 的高灵敏度和快速检测，检测限（LOD）为 0.0064 EU/mL。这些结果表明，适体修饰的多孔 MNs 阵列在临床应用中具有非侵入性提取和检测生物标志物的巨大潜力。
