Biopackaging of minimally invasive ultrasound assisted clot lysis device for stroke treatment

The biopackaging of a minimally invasive sonothrombolysis device (ultrasound-assisted clot lysis device) for acute stroke treatment is proposed and presented. Instead of using thrombolytic medicine (tissue plasminogen activators) in combination with the ultrasound wave for total blood clot dissolution, the proposed sonothrombolysis device uses only pure ultrasound wave generated from Microelectromechanical Systems (MEMS) -based piezoelectric micromachined ultrasonic transducers (pMUTs) that were designed and fabricated in-house. The proposed biopackaging aims to simplify and shorten the clot lysis procedure which could help speed up the recanalization or surgical removal of the blood clots in acute ischemic stroke treatment. The device packaging is composed of two main integrated parts - the three-dimensional (3D) printed United States Pharmacopeia (USP) Class VI plastic material and the 50-mu m thin polyimide flexible printed circuit board (PI FPCB) substrate. The 3D printed USP Class VI plastic material is configured as the drainage catheter of the dissolved clots as well as the custom-fit carrier of the PI FPCB substrate that is coupled and secured onto it. A single layer PI FPCB is used as the substrate of either two or four number of MEMS-based pMUTs, which are attached on it using biocompatible epoxy and wire bonded using 1 mil gold wire. The PI FPCB is also designed such that it is directly compatible with the Flat Flex Cable (FFC) connector of the external circuitry that would trigger the MEMS-based pMUTs to generate acoustic signals as well as measure the viscosity of the blood clot. To drain the dissolved blood clots, the catheter is printed with a number of holes are placed across and around the pMUT location. The catheter tip is rounded-off to remove sharp corners from the plastic material. Buckling analysis is done to simulate stiffness of the catheter when inserted into the brain tissue leading to the center of blood clot. The buckling load of the 3D printed USP Class VI plastic material at a total deformation of 0 - 1 mm at 1 sec is 2038.4N as compared to the buckling load of the silicone rubber (usual catheter material, without the metal guiding rod) which is only 0.128N. The simulation results showed that the 3D printed USP Class VI plastic material will not buckle easily during penetration in the brain tissues or insertion into the blood clot compared to silicone rubber. In order to validate that the combination of materials used in sonothrombolysis device are non-reactive and are not cytotoxic, in vitro cytotoxicity test based on ISO 10993-5 standards is performed. The materials passed.