title: Constant pressure fluid infusion into rat neocortex from implantable microfluidic devices.
abstract: Implantable electrode arrays capable of recording and stimulating neural activity with high spatial and temporal resolution will provide a foundation for future brain computer interface technology. Currently, their clinical impact has been curtailed by a general lack of functional stability, which can be attributed to the acute and chronic reactive tissue responses to devices implanted in the brain. Control of the tissue environment surrounding implanted devices through local drug delivery could significantly alter both the acute and chronic reactive responses, and thus enhance device stability. Here, we characterize pressure-mediated release of test compounds into rat cortex using an implantable microfluidic platform. A fixed volume of fluorescent cell marker cocktail was delivered using constant pressure infusion at reservoir backpressures of 0, 5 and 10 psi. Affected tissue volumes were imaged and analyzed using epifluorescence and confocal microscropies and quantitative image analysis techniques. The addressable tissue volume for the 5 and 10 psi infusions, defined by fluorescent staining with Hoescht 33342 dye, was significantly larger than the tissue volume addressed by simple diffusion (0 psi) and the tissue volume exhibiting insertion-related cell damage (stained by propidium iodide). The results demonstrate the potential for using constant pressure infusion to address relevant tissue volumes with appropriate pharmacologies to alleviate reactive biological responses around inserted neuroprosthetic devices.
authors.affiliation: Biosciences Division, Oak Ridge National Laboratory, Oak Ridge, TN, USA.
authors.forename: S T
authors.initials: ST
authors.lastname: Retterer
authors.forename: K L
authors.initials: KL
authors.lastname: Smith
authors.forename: C S
authors.initials: CS
authors.lastname: Bjornsson
authors.forename: J N
authors.initials: JN
authors.lastname: Turner
authors.forename: M S
authors.initials: MS
authors.lastname: Isaacson
authors.forename: W
authors.initials: W
authors.lastname: Shain
mesh_terms: D000465:Algorithms; D000818:Animals; D001562:Benzimidazoles; D004396:Coloring Agents; D004867:Equipment Design; D005070:Evans Blue; D005456:Fluorescent Dyes; D007091:Image Processing, Computer-Assisted; D015918:Infusion Pumps, Implantable; D008297:Male; D018613:Microscopy, Confocal; D008856:Microscopy, Fluorescence; D036103:Nanotechnology; D019579:Neocortex / Q000502:physiology*; D011312:Pressure; D011419:Propidium; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D001562:Benzimidazoles; D004396:Coloring Agents; D005456:Fluorescent Dyes; D011419:Propidium; D005070:Evans Blue; C017807:bisbenzimide ethoxide trihydrochloride