A blood sampling microsystem for pharmacokinetic applications: Design, fabrication, and initial results

Abstract

This paper describes a microsystem for automated blood sampling from laboratory mice used in pharmacokinetic studies. Intended to be mounted as a “backpack” on a mouse, it uses a microneedle, reservoir, and an actuator to instantaneously prick the animal for a time-point sample, eliminating the need for a tethered catheter with large dead volume. The blood is collected by capillary effect through a 31–33 gauge microneedle (250–210 μm OD) into a ≈1 μL micromachined steel reservoir. The voice coil actuator provides a peak force of ≈300 mN, which amply exceeds the measured piercing force of mouse skin (i.e., 60–85 mN for a 31-gauge needle with 12° bevel). The sampling system was tested in vitro using a mock vessel with adjustable pressure; the reservoir was filled in <0.15 s by a combination of the capillary effect and blood pressure. The system may also be used to sample interstitial fluid, but the absence of blood pressure makes it necessary to enhance the capillary effect of the needle. This is accomplished by either electropolishing the inner surface to make it more hydrophilic or using a polymer wire insert to increase the surface area. The steel surface of the reservoir is also coated with silicon oxynitride by plasma-enhanced chemical vapor deposition to improve its hydrophilicity. Blood from fresh bovine tissue was collected into the reservoir to simulate interstitial fluid sampling. In vivo tests on live, anesthetized mice resulted in successful collection of blood into the reservoir. The possible integration of the device in microanalytical systems and the device scalability for multisampling are discussed.