Integrated electronics and fluidic MEMS for bioengineering.

摘要

Microelectromechanical systems (MEMS) and microelectronics have become enabling technologies for many research areas. This dissertation presents the use of fluidic MEMS and microelectronics for bioengineering applications. In particular, the versatility of MEMS and microelectronics is highlighted by the presentation of two different applications, one for in-vitro study of nano-scale dynamics during cell division and one for in-vivo monitoring of biological activities at the cellular level.;The first application of an integrated system discussed in this dissertation is to utilize fluidic MEMS for studying dynamics in the mitotic spindle, which could lead to better chemotherapeutic treatments for cancer patients. Previous work has developed the use of electrokinetic phenomena on the surface of a glass-based platform to assemble microtubules, the building blocks of mitotic spindles. Nevertheless, there are two important limitations of this type of platform. First, an unconventional microfabrication process is necessary for the glass-based platform, which limits the utility of this platform. In order to overcome this limitation, in this dissertation a convenient microfluidic system is fabricated using a negative photoresist called SU-8. The fabrication process for the SU-8-based system is compatible with other fabrication techniques used in developing microelectronics, and this compatibility is essential for integrating electronics for studying dynamics in the mitotic spindle. The second limitation of the previously-developed glass-based platform is its lack of bio-compatibility. For example, microtubules strongly interact with the surface of the glass-based platform, thereby hindering the study of dynamics in the mitotic spindle. This dissertation presents a novel approach for assembling microtubules away from the surface of the platform, and a fabrication process is developed to assemble microtubules between two self-aligned thin film electrodes on thick SU-8 pedestals. This approach also allows the in-vitro model to mimic the three-dimensionality of the cellular mitotic spindle that is absent in previous work.;The second application of an integrated bioengineering system discussed in this dissertation is to design and fabricate active electronics and sensors for an in-vivo application to monitor neural activity at the cellular level. Temperature sensors were chosen for a first demonstration. In order for temperature sensors to be able to be implanted into brain interfaces, it is necessary for these devices to be fabricated using processes that are compatible with bio-compatible substrates such as glass and plastic. This dissertation addresses this challenge by developing temperature sensors integrated with biasing circuitry using zinc oxide thin film transistors (TFTs) fabricated on polyimide substrates. The integrated sensors show good temperature sensitivity, which is critical for monitoring neural temperature at the cellular level. This dissertation also describes the unique requirements of encapsulating implantable electronics. For instance, encapsulation schemes must be designed in such a way that they both protect electronic devices from extracellular fluids and also do not interfere with the functionality of these devices. In this work, SU-8 is used as a convenient and effective encapsulation layer. Thermal engineering to prevent active electronics from overheating and to ensure accurate temperature measurement from temperature sensors is also discussed, and a synergistic encapsulation and thermal engineering combination is presented.