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 microm OD) into a approximately 1 microL micromachined steel reservoir. The voice coil actuator provides a peak force of approximately 300 mN, which amply exceeds the measured piercing force of mouse skin (i.e., 60-85 mN for a 31-gauge needle with 12 degrees 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.

Microneedles for drug and vaccine delivery

“…In contrast to drug delivery applications, hollow microneedles have also been developed to extract fluids from the body [142, 149, 174–175]. Glass and silicon hollow microneedles were used to obtain interstitial fluid, and stainless steel hollow microneedles were used for blood sampling.…”

Pharmacogenetics in Clinical Pediatrics: Challenges and Strategies

“…Novel methods of noninvasive sampling are ideal for pediatric applications and should be incorporated into ongoing collections and studies. For example, microfluidics technology may allow for repeated and accurate sampling of even our smallest patients in the neonatal intensive care unit [45–47]. Combining these collection methods with high-sensitivity analyses, such as high performance liquid chromatography, already shown to enable determination of concentrations of multiple drugs from a single dried blood spot card [48], creates a feasible way to perform suitably large pharmacogenetic studies in the pediatric population.…”

An Automated Mouse Tail Vascular Access System by Vision and Pressure Feedback

“…Earlier preclinical injection machines access larger targets, such as tumors [14], [15], or perform abdominal blood collection [16]. To access a target as small as the venous system of a small animal, a more maneuverable insertion robot with more degrees of freedom was developed to provide dexterous alignment and needle placement [17].…”