CONTROLLED MICRO RELEASE OF PHARMACOLOGICAL AGENTS - MEASUREMENTS OF VOLUME EJECTED INVITRO THROUGH FINE TIPPED GLASS MICRO-ELECTRODES BY PRESSURE

The amounts of substances delivered by applying pressure to fine. Theta-type, fluid-filled glass microelectrodes were quantitated by in vitro measurement. Relationships between the volumes ejected, the duration of pressure application, and tip size were investigated. The tip sizes ranged between ≤ 0.6 and 1.2 μm o.d. and were suitable for recording intracellularly from cortical neurons in awake cats. With electrodes of tip sizes ≥ 0.6 μm, the volumes of fluid ejected increased linearly with time. Volumes were determined by measuring the activity of ejected radio isotopes or the size of droplets of an aqueous solution expressed into mineral oil. Measurements were obtained over periods of up to 180 sec of pressure application (80 psi). The volumes expressed ranged between 101-105 μm3. The rate of ejection increased as the tip size increased. Tips of 0.6 μm passed up to 2 × 102 μm3; 0.9 μm, up to 4 × 103 μm3 and 1.2 μm up to 5 × 104 μm3 volumes for 30 sec of pressure application. The output rate was greater for ejections of ethanolic solution than for aqueous solution. The repeatability of ejection from individual electrodes was also tested. Relatively consistent, reproducible delivery was found for electrodes with tips between 0.6 and 1.2 μm. The results suggest that the pressure microinjection method affords more predictable, quantitative delivery than the iontophoretic method. Femtomolar (10-15 M) amounts of pharmacologically active substances can be administered by such means. © 1979.