3D-Printed Micro Lens-in-Lens for In Vivo Multimodal Microendoscopy

Multimodal microendoscopes enable co-located structural and molecular measurements in vivo, thus providing useful insights into the pathological changes associated with disease. However, different optical imaging modalities often have conflicting optical requirements for optimal lens design. For example, a high numerical aperture (NA) lens is needed to realize high-sensitivity fluorescence measurements. In contrast, optical coherence tomography (OCT) demands a low NA to achieve a large depth of focus. These competing requirements present a significant challenge in the design and fabrication of miniaturized imaging probes that are capable of supporting high-quality multiple modalities simultaneously. An optical design is demonstrated which uses two-photon 3D printing to create a miniaturized lens that is simultaneously optimized for these conflicting imaging modalities. The lens-in-lens design contains distinct but connected optical surfaces that separately address the needs of both fluorescence and OCT imaging within a lens of 330 mu m diameter. This design shows an improvement in fluorescence sensitivity of >10x in contrast to more conventional fiber-optic design approaches. This lens-in-lens is then integrated into an intravascular catheter probe with a diameter of 520 mu m. The first simultaneous intravascular OCT and fluorescence imaging of a mouse artery in vivo is reported.

Automated summary

Multimodal microendoscopes enable simultaneous structural and molecular measurements in vivo, providing valuable insights into pathological changes associated with diseases. However, different optical imaging modalities have conflicting requirements for lens design, posing a challenge for the fabrication of miniaturized imaging probes. This study demonstrates an optical design using two-photon 3D printing to create a miniaturized lens that is optimized for both fluorescence and optical coherence tomography (OCT) imaging. The lens-in-lens design shows significant improvement in fluorescence sensitivity compared to conventional fiber-optic design approaches, and is successfully integrated into an intravascular catheter probe for simultaneous OCT and fluorescence imaging of a mouse artery in vivo.