The Development and Biocompatibility of Low Temperature Co-Fired Ceramic (LTCC) for Microfluidic and Biosensor Applications

Low temperature co-fired ceramic (LTCC) electronic packaging materials are applied for their electrical and mechanical properties, high reliability, chemical stability and ease of fabrication. Three dimensional features can also be prepared allowing integration of microfluidic channels and cavities inside LTCC modules. Mechanical, optical, electrical, microfluidic functions have been realized in single LTCC modules. For these reasons LTCC is attractive for biomedical microfluidics and Lab-on-a-Chip systems. However, commercial LTCC systems, optimized for microelectrics applications, have unknown cytocompatibility, and are not compatible with common surface functionalization chemistries. The first goal of this work is to develop biocompatible LTCC materials for biomedical applications. In the current work, two different biocompatible LTCC substrate materials are conceived, formulated and evaluated. Both materials are based from well-known and widely utilized biocompatible materials. The biocompatibilities of the developed LTCC materials for in-vitro applications are studied by cytotoxicity assays, including culturing endothelial cells (EC) both in LTCC leachate and directly on the LTCC substrates. The results demonstrate the developed LTCC materials are biocompatible for in-vitro biological applications involving EC. The second goal of this work is to develop functional capabilities in LTCC microfluidic systems suitable for in-vitro and biomedical applications. One proposed application is the evaluation of oxygen tension and oxidative stress in perfusion cell culture and bioreactors. A Clark-type oxygen sensor is successfully integrated with LTCC technique in this work. In the current work, a solid state proton conductive electrolyte is used to integrate an oxygen sensor into the LTCC. The measurement of oxygen concentration in Clark-type oxygen sensor is based on the electrochemical reaction between working electrode and counter electrode. Cyclic voltammetry and chronoamperometry are measured to determine the electrochemical properties of oxygen reduction in the LTCC based oxygen sensor. The reduction current showed a linear relationship with oxygen concentration. In addition, LTCC sensor exhibits rapid response and sensitivity in the physiological range 1─9 mg/L. The fabricated devices have the capabilities to regulate oxygen supply and determination of local dissolved oxygen concentration in the proposed applications including perfusion cell culture and biological assays