Neurochemical dysregulation underlies many pathologies and can be monitored by measuring the composition of brain interstitial fluid (ISF). Existing in vivo tools for sampling ISF do not enable measuring large rare molecules, such as proteins and neuropeptides, and thus cannot generate a complete picture of the neurochemical connectome. Our micro-invasive platform, composed of a nanofluidic pump coupled to a membrane-free probe, enables sampling multiple neural biomarkers in parallel. This platform outperforms the state of the art in low-flow pumps by offering low volume control (single stroke volumes, <3 nl) and bidirectional fluid flow (<100 nl/min) with negligible dead volume (<30 nl) and has been validated in vitro, ex vivo, and in vivo in rodents. ISF samples (<1.5 μL) can be processed via liquid chromatography–tandem mass spectrometry. These label-free liquid biopsies of the brain could yield a deeper understanding of the onset, mechanism, and progression of diverse neural pathologies.

神经化学失调是许多病理的基础，可以通过测量脑间质液 (ISF) 的成分来监测。现有的用于 ISF 采样的体内工具无法测量大型稀有分子，例如蛋白质和神经肽，因此无法生成神经化学连接组的完整图像。我们的微创平台由耦合到无膜探针的纳米流体泵组成，能够并行采样多个神经生物标志物。该平台通过提供低容量控制（单冲程容量，<3 nl）和双向流体流动（<100 nl/min）和可忽略不计的死体积（<30 nl），在低流量泵中表现出色，并且已经在啮齿动物的体外、离体和体内验证。ISF 样本 (<1. 5 μL）可以通过液相色谱-串联质谱进行处理。这些无标记的大脑液体活检可以更深入地了解不同神经病变的发病、机制和进展。