Liquid-shaped microlens for scalable production of ultrahigh-resolution optical coherence tomography microendoscope

Endoscopic optical coherence tomography (OCT) provides real-time, three-dimensional in vivo imaging of luminal organs. Its ability to visualize tissue microstructures without tissue removal makes it superior to traditional biopsy. Current endoscopic OCT systems often operate at 1300 nm with resolutions around 10 µm. To improve resolution and contrast, 800 nm OCT has been developed, offering ~2-4 µm resolution, though at the cost of shallower imaging depth. Miniaturization is vital for accessing small, convoluted organs with minimal invasiveness. Existing miniature OCT probes often utilize all-fiber distal focusing optics (e.g., GRIN fiber, fiber ball lenses), but these suffer from chromatic aberration, low transmission efficiency, and limitations in lens customization. Two-photon 3D microprinting offers an alternative, but is expensive and lacks scalability. This study addresses these limitations by proposing a novel liquid shaping technique for creating high-performance OCT microendoscopes.

The need for high-resolution, minimally invasive imaging of luminal organs has driven research in miniaturized OCT endoscopes. While GRIN fiber and fiber ball lens-based probes are common, they suffer from chromatic aberrations, especially at the advantageous 800 nm wavelength. Achromatic designs using diffractive lenses have been proposed, but with lower transmission efficiency. Two-photon 3D microprinting has emerged as an alternative, creating freeform optics; however, this method is costly and not easily scalable. The surface roughness of 3D-printed optics (10-200 nm) is also suboptimal for high-quality OCT imaging. Therefore, a technique enabling rapid, scalable fabrication of high-quality, miniature OCT probes with corrected aberrations is needed.

The researchers developed a liquid shaping technique to fabricate ultrathin OCT microendoscopes. This technique involves precisely controlling the volume and shape of curable optical liquid (NOA 81) droplets on a wettability-modified substrate. A piezoelectrically actuated dispenser with thermal control ensures accurate liquid dispensing. The substrate's wettability is adjusted to control the contact angle of the liquid droplet, determining the lens's shape. The droplet's volume dictates the lens's size. Using a wettability-modified substrate provides a reflective surface with sub-nanometer roughness, eliminating the need for angle polishing. Circular and elliptical 3D-printed substrates were used to create spheroid and ellipsoid lenses. After dispensing, the droplets are polymerized using a UV lamp. A shrinkage ratio of 7.69% was observed and compensated for in the design. The resulting liquid-shaped microlenses are then integrated with single-mode and non-core fibers to create the OCT microendoscope probe. OpticStudio simulations were used to optimize the design parameters (NCF length, lens radius, incident angle) to minimize back-reflection, chromatic focal shift, spot size, astigmatism, and optimize depth of focus and working distance. The fabricated endoscopes (rigid and flexible versions) were characterized using various techniques (confocal and white-light interferometry profilometry, optical beam profiler). In vivo imaging of rat esophagi, mouse aortas, and mouse brains was performed to evaluate the microendoscopes’ performance.

The liquid shaping technique successfully produced ultrathin (0.6 mm diameter including sheath), aberration-corrected 800-nm OCT microendoscopes. The microlenses achieved sub-nanometer surface roughness (0.84 ± 0.11 nm on curved surface and 0.53 ± 0.11 nm on flat surface), significantly reducing light scattering. The microendoscopes demonstrated ultrahigh resolution (2.4 µm axial resolution, 4.5 µm transverse resolution) and a large depth of field (~200 µm). Simultaneous fabrication of five endoscopes was achieved within 90 minutes, demonstrating scalability. In vivo imaging of a rat esophagus clearly revealed the layered tissue structures, aligning well with histology. Imaging of a mouse aorta showed detailed visualization of tunica intima, media, and adventitia, including elastic lamellae, allowing for precise layer thickness quantification. In vivo deep brain imaging in a mouse demonstrated the ability to image various brain structures (cerebral cortex, corpus callosum, caudate putamen, ventral striatum) with high resolution, revealing details such as striatopallidal fibers. The technique showed excellent results across multiple organs, with high precision and accuracy.

The liquid shaping technique presented overcomes the limitations of existing methods for fabricating miniature OCT endoscopes. It offers significant advantages in terms of cost-effectiveness, scalability, and the ability to precisely control the microlens's characteristics to optimize imaging performance. The ultrahigh resolution achieved at 800 nm, combined with the small size and flexibility of the endoscopes, opens new possibilities for minimally invasive imaging of various small and complex organs. The ability to visualize fine tissue microstructures in vivo is highly relevant for early disease detection and improved diagnostic accuracy.

This study successfully demonstrated a novel liquid shaping technique for the rapid and scalable fabrication of ultrahigh-resolution OCT microendoscopes. The sub-nanometer surface roughness of the liquid-shaped microlenses resulted in excellent imaging performance, surpassing existing methods. The technique’s scalability and ease of implementation suggest significant potential for translation into clinical settings. Future research will focus on incorporating active control methods for microlens shaping, streamlining the fabrication process further, and conducting more extensive in vivo studies in larger animals.

The current study focused on in vivo imaging in small animal models (rats and mice). Further validation in larger animal models is needed before clinical translation. The current liquid shaping technique relies on passive methods for controlling microlens shape. The integration of active control methods (e.g., thermal or electromagnetic fields) could enhance the technique's capabilities. Although five endoscopes were fabricated simultaneously, further automation is required for mass production.