title: Characterization of implantable microfabricated fluid delivery devices.
abstract: The formal characterization of the performance of microfluidic delivery devices is crucial for reliable in vivo application. A comprehensive laboratory technique was developed and used to optimize, calibrate and validate microfabricated fluid delivery devices. In vivo experiments were carried out to verify the accuracy and reliability of the pressure driven devices. Acute guinea pig experiments were conducted to measure the response to alpha-amino-3-hydroxy-5-methyl-4-isoxalone propionic acid, an excitatory neurotransmitter, at multiple locations in the inferior colliculus. A nondimensional parameter, Q, was successfully used to classify devices in terms of geometry alone (i.e., independent of fluid properties). Functional devices exhibited long-term linearity and reliability in delivering single phase, Newtonian fluids, in discrete volumes with a resolution of 500 picoliters at less than 0.45 lbf/in2 (30 mbar) pressure drop. Results for non-Newtonian fluids are not presented here. The acute results showed a proportional increase in the firing rate for delivered volumes of 2 nL up to 10 nL (at rates of between 0.1 and 1 nL/s). Flow characteristics are maintained during acute experiments and post-implant. A control experiment conducted with Ringer solution produced negligible effects, suggesting the results to be truly pharmacological. The experimental techniques employed have proven to be reliable and will be used for future calibration and testing of next generation chronic microfluidic delivery devices.
authors.affiliation: Neural Engineering Laboratory, Biomedical Engineering, The University of Michigan, Ann Arbor, MI 48109-0506, USA. rubenr@umich.edu
authors.forename: Ruben
authors.initials: R
authors.lastname: Rathnasingham
authors.forename: Daryl R
authors.initials: DR
authors.lastname: Kipke
authors.forename: Sanford C
authors.initials: SC
authors.lastname: Bledsoe
authors.forename: John D
authors.initials: JD
authors.lastname: McLaren
mesh_terms: D000200:Action Potentials / Q000187:drug effects / Q000502:physiology; D000818:Animals; D002138:Calibration / Q000592:standards; D017076:Computer-Aided Design; D004867:Equipment Design / Q000379:methods*; D019544:Equipment Failure Analysis / Q000379:methods*; D017022:Flow Injection Analysis; D006168:Guinea Pigs; D007245:Inferior Colliculi / Q000187:drug effects / Q000502:physiology; D015918:Infusion Pumps, Implantable; D007263:Infusions, Parenteral / Q000295:instrumentation* / Q000379:methods*; D044085:Microfluidics / Q000295:instrumentation* / Q000379:methods*; D008904:Miniaturization / Q000379:methods; D009474:Neurons / Q000187:drug effects / Q000502:physiology; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid / Q000008:administration & dosage
chemical_list: D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid