3D-Printed Glass Micro-Optical System for Biomedical and Clinical Applications - Abstract Micro-optics play a crucial role in biomedical imaging, particularly in endoscopic systems, providing unparalleled advantages in compactness and resolution. However, as the dimensions of micro-optical systems shrink to address clinical demands, the limitations of traditional systems become more apparent, often resulting in potential compromises in optical performance. Recognizing the growing demand in medical arenas and current optical fabrication constraints, we introduce a novel glass micro-optical system where all components are fabricated together as a single unit, with the optical portions transparent and the non-optical portions black. This eliminates the need for mechanical components for structural integrity or to block stray light. This innovation is transformative rather than incremental, enabled solely by the proposed 3D printing techniques and materials. Leveraging the support from the R21CA268190 grant in recent years, we've demonstrated the merits and potential of 3D-printed glass micro- optical systems. By pioneering new printing materials and novel two-photon polymerization (TPP) printing processes, we've developed glass micro-optical systems possessing attributes unattainable through any other manufacturing methods and commercial system, such as GRIN lens. Central to our proposed glass micro-optical system is its holistic integration, which circumvents traditional assembly and alignment hurdles. We've also pioneered materials with a higher refractive index, innovative printing techniques for localized transparency control, and multi-material printing to enhance imaging performance. Our goal is to develop and promote glass micro-optical systems tailored for biomedical and clinical imaging. We will first build a custom 3D printing system with a large field of view (FOV) to achieve high throughput and enable the printing of large glass micro-optical systems, thereby overcoming the limitations of commercially available TPP printers. Concurrently, we will investigate new printing materials with higher refractive indices to enhance imaging quality. We'll also fine-tune printing techniques that control local transparency to boost image contrast and optimize multi-material printing process to improve system performance across a wide spectrum. Ultimately, we aim to design and fabricate three types of glass micro-optical systems, evaluate and compare their performances with commercial GRIN lenses and microscope objective in white light, autofluorescence, and confocal imaging modes with tissue samples. The anticipated impact of this project is substantial, heralding the advent of compact glass micro-optical systems that were previously inconceivable, featuring unparalleled imaging capabilities. Such advancements could expedite the transition of revolutionary imaging tools from the lab to tangible clinical settings. This endeavor promises not only innovations in imaging capabilities but also cost-effective rapid prototyping solutions, unlocking previously unattainable applications in biomedical and clinical imaging.