Proof of Concept for Sustainable Manufacturing of Neural Electrode Array for In Vivo Recording.

Increasing requirements for neural implantation are helping to expand our understanding of nervous systems and generate new developmental approaches. It is thanks to advanced semiconductor technologies that we can achieve the high-density complementary metal-oxide-semiconductor electrode array for the improvement of the quantity and quality of neural recordings. Although the microfabricated neural implantable device holds much promise in the biosensing field, there are some significant technological challenges. The most advanced neural implantable device relies on complex semiconductor manufacturing processes, which are required for the use of expensive masks and specific clean room facilities. In addition, these processes based on a conventional photolithography technique are suitable for mass production, which is not applicable for custom-made manufacturing in response to individual experimental requirements. The microfabricated complexity of the implantable neural device is increasing, as is the associated energy consumption, and corresponding emissions of carbon dioxide and other greenhouse gases, resulting in environmental deterioration. Herein, we developed a fabless fabricated process for a neural electrode array that was simple, fast, sustainable, and customizable. An effective strategy to produce conductive patterns as the redistribution layers (RDLs) includes implementing microelectrodes, traces, and bonding pads onto the polyimide (PI) substrate by laser micromachining techniques combined with the drop coating of the silver glue to stack the laser grooving lines. The process of electroplating platinum on the RDLs was performed to increase corresponding conductivity. Sequentially, Parylene C was deposited onto the PI substrate to form the insulation layer for the protection of inner RDLs. Following the deposition of Parylene C, the via holes over microelectrodes and the corresponding probe shape of the neural electrode array was also etched by laser micromachining. To increase the neural recording capability, three-dimensional microelectrodes with a high surface area were formed by electroplating gold. Our eco-electrode array showed reliable electrical characteristics of impedance under harsh cyclic bending conditions of over 90 degrees. For in vivo application, our flexible neural electrode array demonstrated more stable and higher neural recording quality and better biocompatibility as well during the 2-week implantation compared with those of the silicon-based neural electrode array. In this study, our proposed eco-manufacturing process for fabricating the neural electrode array reduced 63 times of carbon emissions compared to the traditional semiconductor manufacturing process and provided freedom in the customized design of the implantable electronic devices as well.

Mineral Nanomedicine to Enhance the Efficacy of Adjuvant Radiotherapy for Treating Osteosarcoma.

It is vital to remove residual tumor cells after resection to avoid the recurrence and metastasis of osteosarcoma. In this study, a mineral nanomedicine, europium-doped calcium fluoride (CaF2:Eu) nanoparticles (NPs), is developed to enhance the efficacy of adjuvant radiotherapy (i.e., surgical resection followed by radiotherapy) for tumor cell growth and metastasis of osteosarcoma. In vitro studies show that CaF2:Eu NPs (200 µg/mL) exert osteosarcoma cell (143B)-selective toxicity and migration-inhibiting effects at a Eu dopant amount of 2.95 atomic weight percentage. These effects are further enhanced under X-ray irradiation (6 MeV, 4 Gy). Furthermore, in vivo tests show that intraosseous injection of CaF2:Eu NPs and X-ray irradiation have satisfactory therapeutic efficacy in controlling primary tumor size and inhibiting primary tumor metastasis. Overall, our results suggest that CaF2:Eu NPs with their osteosarcoma cell (143B)-selective toxicity and migration-inhibiting effects combined with radiotherapy might be nanomedicines for treating osteosarcoma after tumor resection.