PROJECT SUMMARY/ABSTRACT Microsystems for the detection of biomolecules can play important roles in biomedical research, clinical diagnosis, food safety, homeland security and pharmaceutical testing. The research objective of this proposal is to develop an ultrasensitive and high-throughput complementary metal–oxide– semiconductor (CMOS) sensors including over 10,000 sensor units on a 1-inch chip that could provided high-resolution spectroscopic information with combined features of label-free, high sensitivity, high throughput, small size, and easy integration with existing electronics. Each sensor unit is composed for surface-functionalized silica-based high-quality whispering-gallery-mode (WGM) resonators that approximate the size of eukaryotic cells for ultra-sensitive label-free biosensing of specific proteins, biomarkers and protein-protein interactions. The basis for the technology is the physical associations and interactions of biomolecules on a microresonator surface alter the residence time of photons in a way that can be measured and quantified by a novel photonic crystal (PC) integrated CMOS spectrometer. Moreover, the proposed PC-CMOS is expected to achieve a video-frame rate of spectroscopy with a large field of view (FOV) (2 cm × 2 cm) and high spectral resolution (1 pm). The unique features of the proposed sensor lie in two advantages: (1) ultrasensitivity enabled by significantly enhanced light-matter interactions in high-quality WGM optical microresonators; and (2) high-throughput sensing mechanisms adopted from CMOS originally developed in the semiconductor industry for communications and electronic products. Our objective will be achieved by completing the following three specific aims. Aim 1 will develop PC slab spectrometer on a CMOS chip for wide-field high-resolution spectroscopy. Aim 2 will design, fabricate, measure, and optimize the surface-grating-waveguide-coupled WGM microsensor arrays. Aim 3 will demonstrate resonance-enhanced high-resolution CMOS spectrometer. The proposed research contains three main innovations: (1) the novel WGM sensor arrays are expected to offer several orders of magnitude higher sensitivity than existing sensing technologies, such as ELISA; (2) PC slab spectrometer on a CMOS chip, which enables a single-shot detection of over 10,000 optical mode spectra of the WGM microsensors and resonance-enhanced Raman spectroscopy; (3) integrating ultrasensitive WGM sensors with CMOS technologies to realize a new system leading to a disruptive technology for sensing applications where high sensitivity and high throughput are desired. This project is significant because successful completion of this work will lay the foundation for the development of a new biosensor with great potential to advance clinical diagnosis and biomedical research by revolutionizing conventional sensing technologies by leveraging the existing technologies in semiconductor industries. If successful, the technology developed in thi...