Platform for micro-invasive membrane-free biochemical sampling of brain interstitial fluid
Author(s)Raman, Ritu; Rousseau, Erin Byrne; Wade, Michael; Tong, Allison; Cotler, Max Joseph; Kuang, Jenevieve; Lugo, Alejandro Aponte; Zhang, Elizabeth Y.; Graybiel, Ann M; White, Forest M.; Langer, Robert S; Cima, Michael J.; ... Show more Show less
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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.
DepartmentHarvard University--MIT Division of Health Sciences and Technology; Center for Precision Cancer Medicine; McGovern Institute for Brain Research at MIT; Massachusetts Institute of Technology. Department of Brain and Cognitive Sciences; Massachusetts Institute of Technology. Department of Biological Engineering; Massachusetts Institute of Technology. Department of Chemical Engineering; Massachusetts Institute of Technology. Department of Materials Science and Engineering; Koch Institute for Integrative Cancer Research at MIT
American Association for the Advancement of Science (AAAS)
Raman, Ritu et al. "Platform for micro-invasive membrane-free biochemical sampling of brain interstitial fluid." Science Advances 6, 39 (September 2020): eabb0657 © 2020 American Association for the Advancement of Science
Final published version