Ultrabright Plasmonic-Fluor Nanosensor-Enabled Noninvasive Management of Pediatric Nephrotic Syndrome

小儿肾病综合征（NS）是一种使人衰弱的儿童肾脏疾病，以蛋白尿、低白蛋白血症和进行性肾功能丧失为特征。此外，约占儿科终末期肾病10%的类固醇耐药NS可能需要长期使用免疫抑制剂，这可能导致肾毒性。小儿静脉穿刺难度大，单次及2个月内最大采血量限制小，特别是新生儿、婴幼儿，限制了NS活动期肾功能的密切监测。此外，尿试纸试验作为一种半定量且不总是可靠的试验，是一种评估治疗反应的粗糙方法。它也无法评估可能因体积收缩、常规使用利尿剂和血管紧张素转换酶抑制剂以及药物引起的急性肾毒性而损害的肾功能。因此，开发一种创新的、无痛的、无体积提取的、高灵敏度的生物诊断平台是提高小儿神经痛患者临床护理水平的必要条件。

Pediatric nephrotic syndrome (NS), characterized by proteinuria, hypoalbuminemia and progressive loss of kidney function, is a debilitating childhood kidney disease. In addition, steroid-resistant NS, accounting for about 10% of end- stage kidney disease in the pediatric population, may require long-term use of immunosuppressants that can cause nephrotoxicity. The daunting difficulty in pediatric venipuncture, as well as the small volume limit of maximum blood draw allowed for a single draw and within 2 months, especially in neonates, infants and young children, has limited close monitoring of kidney function in the active phase of NS. Moreover, urine dipstick test, as a semi-quantitative and not- always-reliable assay, is a crude way of evaluating the treatment response. It is also unable to assess the kidney function that may be compromised by volume contraction, routine use of diuretics and angiotensin-converting enzyme inhibitors, and drug-induced renal toxicity acutely. Thus, development of an innovative, pain-free and volume extraction-free, and highly sensitive biodiagnostic platform is imperative to improve the clinical care for pediatric NS patients. Bioanalyte-rich dermal interstitial fluid (ISF) provides a novel opportunity to achieve painless and effective biodiagnostic technologies. However, the clinical utility of ISF is limited by the current technology. Our goal is to develop our newly invented ultrabright plasmonic-fluor (PF)-enabled microneedle (MN) technology (PF-MN) as an ultrasensitive and minimally-invasive diagnostic tool for rapid sampling and quantification of ISF blood urea nitrogen (BUN) and creatinine (Cr) in point-of-care settings and at home. To accomplish our research goals, we will utilize a highly reproducible hereditary NS mouse model. In this preclinical model, we aim to determine concentrations of BUN and Cr in the dermal ISF by using PF-enhanced competitive immunoassay performed on MN. Furthermore, we will correlate their concentrations derived from MN-sampled ISF, extracted ISF and serum. A successful completion of our pioneering proposal may lead to a paradigm-shift in the newborn and pediatric diagnostics. It will also pave the way for future translational study in pediatric NS patients.