Design and characterization of a microfabricated hydrogen clearance blood flow sensor.
Modern cerebral blood flow (CBF) detection favors the use of either optical technologies that are limited to cortical brain regions, or expensive magnetic resonance. Decades ago, inhalation gas clearance was the choice method of quantifying CBF, but this suffered from poor temporal resolution. Electrolytic H2 clearance (EHC) generates and collects gas in situ at an electrode pair, which improves temporal resolution, but the probe size has prohibited meaningful subcortical use.



We microfabricated EHC electrodes to an order of magnitude smaller than those existing, on the scale of 100μm, to permit use deep within the brain.



Novel EHC probes were fabricated. The devices offered exceptional signal-to-noise, achieved high collection efficiencies (40-50%) in vitro, and agreed with theoretical modeling. An in vitro chemical reaction model was used to confirm that our devices detected flow rates higher than those expected physiologically. Computational modeling that incorporated realistic noise levels demonstrated devices would be sensitive to physiological CBF rates.



The reduced size of our arrays makes them suitable for subcortical EHC measurements, as opposed to the larger, existing EHC electrodes that would cause substantial tissue damage. Our array can collect multiple CBF measurements per minute, and can thus resolve physiological changes occurring on a shorter timescale than existing gas clearance measurements.



We present and characterize microfabricated EHC electrodes and an accompanying theoretical model to interpret acquired data. Microfabrication allows for the high-throughput production of reproducible devices that are capable of monitoring deep brain CBF with sub-minute resolution.
Department of Chemistry, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA. Electronic address: waltonlr@email.unc.edu.
Lindsay R
LR
Walton
Department of Chemistry, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA. Electronic address: martin.edwards@utah.edu.
Martin A
MA
Edwards
Department of Chemistry, North Carolina State University, Raleigh, NC, USA. Electronic address: gsmccart@ncsu.edu.
Gregory S
GS
McCarty
Department of Chemistry, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA; Neuroscience Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA. Electronic address: rmw@unc.edu.
R Mark
RM
Wightman
D001774:Blood Chemical Analysis / Q000295:instrumentation; D002560:Cerebrovascular Circulation / Q000502:physiology; D003198:Computer Simulation; D004567:Electrodes, Implanted; D004867:Equipment Design; D020342:Finite Element Analysis; D006859:Hydrogen / Q000032:analysis*; D055616:Microtechnology; D009638:Norepinephrine / Q000378:metabolism; D010100:Oxygen / Q000032:analysis; D010984:Platinum; D015203:Reproducibility of Results
D010984:Platinum; D006859:Hydrogen; D010100:Oxygen; D009638:Norepinephrine
COMSOL Multiphysics; Electrolysis; Gas clearance; Photolithography; Platinum electrode