The development of personalized healthcare solutions is a complex and multifaceted challenge that requires synergistic collaboration and cross-fertilization between multiple disciplines, including microelectronics, nanotechnology, materials science, and biotechnology. As numerous biomedical applications necessitate the precise regulation and observation of various biological systems at the microscale, developing integrated microsystems with functionalities that span diverse domains, such as electrical, mechanical, and optical, has become imperative in paving the way for next-generation biomedical devices.
Nevertheless, as the number of microsystems within a biomedical device escalates, a pressing need emerges to interconnect these independent microsystems using an approach that meets the constraints imposed per each particular context. Wire bonding, for instance, is one of the most widely known and used methods to establish electrical connections between chips and packages. However, wire-bonded microsystems may be inadequate to fit in applications confined by the available physical space and whereby aspects such as reliability and biocompatibility are paramount. Specifically deserving attention is the increased footprint and the introduction of protrusions that may jeopardize an effective interface of biomedical devices with biological systems. Therefore, it becomes essential to devise seamless connections between these microsystems for enhanced robustness, electrical performance, compactness, and improved physical conformability to biological structures.
This doctoral research was driven by the increasing demand for microsystem integration alternatives in the biomedical field and the need to develop advanced biomedical devices with improved functionality and performance. Monolithic fabrication was the principal method of establishing a seamless integration between distinct microsystems: integrated circuits—essential for the signal conditioning of transducers—and micro-electromechanical systems—excellent for implementing functionalities at the microscale via precise micromachining delicate structures on high-quality materials. Two novel biomedical devices were devised to achieve this objective: an organ-on- a-chip system for cell-culture experimentation equipped with an analog-compatible, cost-effective, BiCMOS-based temperature sensor and a stretchable polydimethyl-siloxane membrane; and an artifact-resilient optrode optimized for ultralow-noise measurements of infraslow brain activity. The latter benefited from dual-gate, low-noise, p-channel JFETs based on a BiFET technology and deep reactive ion etching on a silicon-on-insulator wafer for micromachining nonrectilinear features on the probe— essential for creating application-oriented solutions that interface better with biological structures.
Both devices were designed based on a unique awareness-oriented co-design methodology that aids the device architect in undertaking design decisions of various process-related hurdles entailing co-fabrication. This methodology, namely “holistic iterative co-design thinking”, offers an iterative co-design process that facilitates the early identification of integration obstacles related to the manufacturing process. One of the key procedures in this methodology refers to functionally decomposing a multidimensional complex design problem into a set of individual one-dimensional problems that are less complex to solve. As a result, the (co)-design is iteratively readjusted, significantly saving time and resources.
This dissertation also takes a new standpoint into the existing monolithic fabrication modalities, proposes a new taxonomy, clarifies terminologies, and addresses a novel co-fabrication technique: IC-interlaced-MEMS, employed for cost- effectively co-fabricating the organ-on-a-chip system described in Chapter 4. The IC-interlaced-MEMS is similar to its “sibling” IC-interleaved-MEMS. The distinction lies primarily in their degree of process orthogonality. While the IC-interleaved-MEMS benefits from fully orthogonalizing process steps between the IC and MEMS domains, the IC-interlaced-MEMS trades orthogonality for process simplification and enhanced lithographic pipeline workflow. These benefits promise to leverage the construction of next-generation biomedical devices that interact with biological systems via specialized, large-area transducers.