Implantable micropump technologies for murine intracochlear infusions

Abstract

Due to the very small size of the mouse inner ear, 600 nL volume, developing effective, controlled infusion systems is quite challenging. Key technologies have been created to minimize both size and power for an implantable pump for murine intracochlear infusions. A method for coupling fine capillary tubing to microfluidic channels is presented which provides low volume, biocompatible interconnects withstanding pressures as high as 827 kPa (120 psi) and consuming less than 20 nL of volume exiting in-plane with the pump. Surface micromachined resistive bridges integrated into the flow channel for anemometry based flow rate measurement have been optimized for low power operation in the ultra-low flow rate regime. A process for creation of deformable diaphragms over pump chambers with simultaneous coating of the microfluidic channels has been developed allowing integration of a biocompatible fluid flow path. These advances represent enabling capabilities for a drug delivery system suitable for space constrained applications such as subcutaneous implantation in mice.

Age-related hearing loss: prevention of threshold declines, cell loss and apoptosis in spiral ganglion neurons

“…Next, the slides went into 70% alcohol for 30 sec, stained with BBC Special Eosin II for 1 min, dehydrated with BBC S2*Histo 5 × 20 sec, and cleared in xylene and coverslipped using a permanent mounting media (Fisher Scientific, Pittsburgh, PA). Semi-automated cell counts were made using the MetaMorph imaging system with a Leica DMR microscope, using procedures similar to our previous investigations of the mouse aging auditory system [ 61 , 68 , 83 ].…”

Stable release of BDNF from the fibroblast cell line NIH3T3 grown on silicone elastomers enhances survival of spiral ganglion cells in vitro and in vivo

“…Sustained systemic delivery to the inner ear may be problematic since neurotrophic factors have a short serum half-life and do not permeate the bloodecochlea barrier (Kishino et al, 2001). To enable local administration different application systems like osmotic pumps for infusion of drugs into the inner ear of deafened guinea pigs and mice (Johnson et al, 2010;Staecker et al, 2010) have been studied previously. Despite the benefits of pump delivery systems allowing regulation of the quantity of fluid applied, this method of drug administration may increase surgical complexities, risk of infection and damage of residual hearing (McCall et al, 2010).…”

A microfluidic reciprocating intracochlear drug delivery system with reservoir and active dose control

“…Excellent review articles give an overview of microscale drug delivery devices developed for a variety of therapies 33–36 . Among the emerging devices engineered specifically for intracochlear delivery, Johnson et al fabricated a tapered silicone interface for sealing to a rodent cochleostomy 37 and also designed a cannula interface and flow sensor for integration with a micropump 38 . Others have tested modified cochlear prosthesis electrodes that contain a microchannel for drug transport 39, 40 .…”