RT Journal Article
SR Electronic
T1 Platform for micro-invasive membrane-free biochemical sampling of brain interstitial fluid
JF Science Advances
JO Sci Adv
FD American Association for the Advancement of Science
SP eabb0657
DO 10.1126/sciadv.abb0657
VO 6
IS 39
A1 Raman, Ritu
A1 Rousseau, Erin B.
A1 Wade, Michael
A1 Tong, Allison
A1 Cotler, Max J.
A1 Kuang, Jenevieve
A1 Lugo, Alejandro Aponte
A1 Zhang, Elizabeth
A1 Graybiel, Ann M.
A1 White, Forest M.
A1 Langer, Robert
A1 Cima, Michael J.
YR 2020
UL http://advances.sciencemag.org/content/6/39/eabb0657.abstract
AB 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.