Annaida Technologies SA, Lausanne, Switzerland.
Microsystems Laboratory, École Polytechnique Fédérale de Lausanne (EPFL), Lausanne, Switzerland.
Sci Rep. 2020 Oct 27;10(1):18306. doi: 10.1038/s41598-020-75480-0.
Performing chemical analysis at the nanoliter (nL) scale is of paramount importance for medicine, drug development, toxicology, and research. Despite the numerous methodologies available, a tool for obtaining chemical information non-invasively is still missing at this scale. Observer effects, sample destruction and complex preparatory procedures remain a necessary compromise. Among non-invasive spectroscopic techniques, one able to provide holistic and highly resolved chemical information in-vivo is nuclear magnetic resonance (NMR). For its renowned informative power and ability to foster discoveries and life-saving applications, efficient NMR at microscopic scales is highly sought after, but so far technical limitations could not match the stringent necessities of microbiology, such as biocompatible handling, ease of use, and high throughput. Here we introduce a novel microsystem, which combines CMOS technology with 3D microfabrication, enabling nL NMR as a platform tool for non-invasive spectroscopy of organoids, 3D cell cultures, and early stage embryos. In this study we show its application to microlivers models simulating non-alcoholic fatty liver disease, demonstrating detection of lipid metabolism dynamics in a time frame of 14 days based on 117 measurements of single 3D human liver microtissues.
在纳升（nL）尺度上进行化学分析对于医学、药物开发、毒理学和研究至关重要。尽管有许多可用的方法，但在这个尺度上仍然缺乏一种非侵入性获取化学信息的工具。观察者效应、样品破坏和复杂的准备程序仍然是必要的妥协。在非侵入性光谱技术中，有一种能够提供整体和高分辨率的体内化学信息的技术是核磁共振（NMR）。由于其众所周知的信息功能和促进发现和拯救生命的应用的能力，在微观尺度上高效的 NMR 受到高度追捧，但到目前为止，技术限制无法满足微生物学的严格要求，例如生物相容性处理、易于使用和高通量。在这里，我们介绍了一种新的微系统，它将 CMOS 技术与 3D 微加工相结合，使 nL NMR 成为用于类器官、3D 细胞培养物和早期胚胎的非侵入性光谱学的平台工具。在这项研究中，我们展示了它在模拟非酒精性脂肪肝的微肝模型中的应用，证明了基于对单个 3D 人类肝微组织的 117 次测量，能够在 14 天的时间内检测到脂质代谢动力学。
