4.8 Article

Platform for micro-invasive membrane-free biochemical sampling of brain interstitial fluid

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SCIENCE ADVANCES
卷 6, 期 39, 页码 -

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AMER ASSOC ADVANCEMENT SCIENCE
DOI: 10.1126/sciadv.abb0657

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资金

  1. NIH (National Institute of Biomedical Imaging and Bioengineering) [R01 EB016101, R01 EB027717-01A1]
  2. Center for Precision Cancer Medicine at MIT
  3. Koch Institute Support (core) grant from the National Cancer Institute [P30-CA14051]
  4. AAAS L'Oreal USA For Women in Science Fellowship
  5. NASEM Ford Foundation Fellowship
  6. NSF Graduate Research Fellowship [2016220817, 1122374]
  7. NIH (National Institute of Mental Health) [R01 MH060379]
  8. Saks Kavanaugh Foundation

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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 mu L) 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.

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