PhD Thesis Defense by Javier Cuenca Michans, predoctoral researcher at IMB-CNM.
Supervisors:
- Antoni Baldi Coll
- Josep Maria Margarit Taulé
- Francesc Serra Graells
PhD Committee:
- Joan Bausells Roigé
- Maria Aranzazu Uranga del Monte
- Nicolas Bernard Gordon Moser
University: Universitat Autònoma de Barcelona
About the thesis
Abstract: The integration of sensors in CMOS technology has transformed the field of chemical and biological sensing by enabling high integration density and low production costs. In particular, Ion-Sensitive Field-Effect Transistors (ISFETs) have gained interest due to their versatility and direct integration into standard CMOS processes. When integrated in large-scale arrays, their performance is enhanced by enabling parallel real-time ion detection, which has induced a revolution in biomedical applications such as DNA sequencing. Simultaneously, lab-on-chip (LoC) systems have emerged as compact integrated platforms capable of performing complex biochemical analyses on a single chip. These platforms push the boundaries of miniaturization, proving advantageous over traditional benchtop systems by greatly reducing costs and analysis time. When these LoC systems are built around CMOS integrated circuits, their sensing capabilities can be greatly enhanced, evolving into lab-on-CMOS platforms. This PhD thesis explores the integration of CMOS ISFET arrays into lab-on-CMOS platforms to realize compact, highly integrated, and intelligent biochemical sensing systems by combining the real-time ion sensing of CMOS ISFET arrays with the miniaturization and low integration costs of lab-on-CMOS platforms. A novel ISFET pixel architecture is proposed addressing known limitations of ISFETs while providing in-pixel analog-to-digital conversion. This digital ISFET pixel architecture is implemented in a commercial low-power 65-nm CMOS process through an 8x8 and a 16x16 ISFET array, and validated both at electrical and electrochemical level. In addition, the enhancement of pH sensitivity and reduction of electrochemical drift is demonstrated on CMOS ISFETs by post-processing them with a HfO2 atomic layer deposition. Two fabrication methodologies for lab-on-CMOS integration and packaging are demonstrated by integrating microfluidic structures with the fabricated 65-nm CMOS ISFET arrays. These simple and reliable fabrication methods are compatible with cost-effective biomedical applications, and have been developed targeting two distinct needs: (i) integration and packaging of mm-scale CMOS chips into cm-scale microfluidic structures, and (ii) direct on-chip integration of microfluidics. The developed lab-on-CMOS platforms are explored in three biomedical applications. First, the miniaturization capabilities of such platforms are exploited to produce a reference-electrode-free multi-ionic probe capable of sub-mL volume measurements. The second application leverages the high integration density of CMOS ISFET arrays to enable compact and low-cost digital immunoassays for biomarker detection. Finally, the latter exploits neuromorphic circuit design strategies to mitigate ISFET non-idealities, allowing uninterrupted spatiotemporal detection of ion dynamics for understanding biochemical and physiological processes.