System and method for scalable fabrication of high performance optical coherence tomography endoscopes

Abstract

Endoscopic optical coherence tomography (OCT) provides diagnostic images of visceral organs and guides interventional therapy in real time. The invention provides a method and a system for manufacturing a high-performance optical coherence tomography endoscope through liquid forming. The method and the system are used for manufacturing the high-performance optical coherence tomography endoscope working in different wavelength ranges quickly and extendibly. The methods and systems enable flexible customization of free form lenses with sub-nanoscale optical surface roughness by adjusting the minimum energy state of a curable optical liquid on a substrate with improved wettability and precisely controlling the liquid volume and physical boundaries on the substrate. Therefore, multiple endoscopes, such as 800 nm OCT endoscopes having a diameter of about 0.6 mm, including rigid endoscopes and flexible endoscopes, can be manufactured at the same time. The liquid forming methods and systems provide a novel method for mass production of low cost, high performance OCT endoscopes.

Description

[0001] Cross-reference to related applications

[0002] This application claims the benefit of U.S. patent application No. 63 / 538,716, filed on September 15, 2023, the entire contents of which are incorporated by reference into this application, including any tables, figures, or drawings. Technical Field

[0003] The present invention relates to endoscopes and manufacturing techniques. Background Art

[0004] Optical coherence tomography (OCT) combines the features of both ultrasound and confocal microscopy, bridging the gap between these two imaging modalities. Although ultrasound imaging provides centimeter-level imaging depth, its resolution is limited to about hundreds of microns. In contrast, confocal microscopy provides submicron resolution, but its imaging depth is limited to at most 100 microns in tissue. OCT technology solves these limitations. This technology provides an axial resolution of 1 to 10 μm and a tissue imaging depth of approximately 1 to 3 mm. Therefore, OCT is particularly suitable for high-resolution imaging of superficial tissue layers, such as the mucosa of luminal organs.

[0005] As one of the first clinical applications, endoscopic OCT has become a valuable tool for providing diagnostic images of endoluminal structures. This technology allows for near-histological quality visualization of tissue microarchitecture and provides histopathological information. This technology overcomes the limitations of traditional biopsies and enables three-dimensional (3D) volume sampling over large areas without the need to remove tissue. In clinical practice, imaging of luminal organs requires the use of high-performance disposable OCT endoscopes to accurately resolve subtle pathological changes associated with the disease, such as the fibrous cap of atherosclerosis.

[0006] Currently, disposable OCT endoscopes are mainly manufactured using gradient refractive index (GRIN) lenses / fibers or fiber spherical lenses. However, OCT endoscopes composed of GRIN lenses / fibers have significant chromatic and spherical aberrations, especially in the short wavelength range (e.g., 800nm ​​and visible light range). Alternatively, achromatic OCT endoscopes can be developed using distal fiber-fused spherical lenses. However, fiber-fusion technology lacks the necessary flexibility to customize spherical lenses that achieve the best balance between working distance, resolution, and depth of focus (DOF). Manufacturing reflective surfaces on fiber spherical lenses involves a labor-intensive angle polishing process, which poses a challenge to obtaining the desired optical surface roughness. In addition, both manufacturing methods require time-consuming and complex assembly processes (including high-precision optical alignment) and require trained experts. Therefore, traditional manufacturing methods still lack scalability and incur high adoption costs in clinical settings. Recently, two-photon 3D printing has been used to produce free-form side-deflecting optics at the tip of a single-mode fiber (SMF), enabling the development of OCT endoscopes with diameters of approximately 0.5 to 1300 nm. However, this technology is costly and lacks scalability. In addition, the surface roughness of 3D printed optics is between 10 and 200 nm, which is not suitable for OCT imaging.

[0007] Therefore, new methods need to be developed for scalable generation of low-cost, high-performance OCT endoscopes. Improved OCT endoscopes and manufacturing methods are needed to enable mass production (low cost) and customization (highly customizable performance to meet different clinical application needs). Summary of the invention

[0008] In one aspect, the present invention relates to a liquid molding-based method and system for scalable manufacturing of low-cost, disposable OCT endoscopes with highly customizable properties.

[0009] In a first aspect, the present invention relates to a method based on liquid molding technology, which facilitates the rapid and mass production of self-assembled free-form optical devices (including lenses and mirrors) with sub-nanometer surface roughness and customized shapes and structures to effectively correct optical aberrations and provide desired imaging performance.

[0010] In a second aspect, the present invention relates to an automated manufacturing system that enables rapid assembly of free-form optics into fiber-optic probes of OCT endoscopes, thereby eliminating costly and time-consuming manufacturing processes such as lens polishing. In addition, the manufacturing system does not require high-precision optical alignment and requires minimal human expertise in operation.

[0011] In some embodiments, a novel liquid molding technique is provided that facilitates the rapid and simultaneous fabrication of pre-designed side-focusing lenses on the tip of an optical fiber for ultra-high-resolution OCT endoscopes. By adjusting the minimum energy state of a curable optical liquid on a substrate surface with customized wetting properties, and controlling the volume of the droplet and its physical boundaries on the substrate, the size and shape of the distal lens of the OCT probe can be flexibly customized. This helps correct optical aberrations and optimize imaging performance. This technology also eliminates the need for angle polishing and produces liquid-like lenses with sub-nanometer surface roughness. Using this technology, aberration-corrected OCT endoscopes can be simultaneously manufactured. As a primary example, the diameter of the endoscope produced is approximately 0.6 mm (including the protective sleeve) and provides an ultra-high resolution of 2.4 μm × 4.5 μm (axial and lateral resolution, respectively). In addition, the imaging performance, mechanical flexibility, and minimal invasiveness of these endoscopes were demonstrated by imaging the esophagus of rats and the aorta and brain of mice. This method also facilitates the scalable manufacture of low-cost, high-performance OCT endoscopes for minimally invasive and ultra-high-resolution optical biopsy in clinical settings. BRIEF DESCRIPTION OF THE DRAWINGS

[0012] Figures 1A to 1G is a schematic diagram of using liquid molding technology to manufacture optical lenses, where Figure 1A Depicted is the production of lenses on substrates with improved wettability using a piezoelectrically actuated dispenser with thermal control, Figure 1B Depicted is a liquid-like lens-based OCT endoscope for in vivo imaging in small, complex luminal organs (e.g., coronary artery vessels), Figure 1C and Figure 1D is a schematic diagram of an optical liquid on a substrate (without physical boundaries). Lenses with the same liquid volume (V1) have different radii (i.e., r1-r3) and contact angles (i.e., θ1-θ3) on substrates of different wettability (W1-W3), where when the liquid volume on a substrate of the same wettability W4 increases from V1 to V3, the radius of the lens increases from r4 to r6 while maintaining a contact angle of θ4, Figure 1E Depicted is the production of a spherical lens using a substrate with a circular border. The radius and contact angle of the lenses produced with different liquid volumes are denoted by r1, r2 and θ1, θ2, θ3, respectively. Figure 1F Depicts the fabrication of an ellipsoidal lens on a substrate with an elliptical boundary. The semi-major axis lengths (i.e., m1, m2, m3), semi-minor axis lengths (i.e., n1 and n2), and the distance from θ in the xz plane to the substrate are shown when different liquid volumes are used on the substrate. x1 to θ x3 The contact angle of θ and the y1 to θ y3The contact angle. Please note that n1 = m1, n2 = m2, θ x1 =θ y1 , and θ x2 =θ y2 , Figure 1G Depicted is the fabrication of a spherical lens whose shape is actively controlled by temperature T1-T3. Before applying thermal control, the substrates have the same wettability W5. According to some embodiments of the present invention, after the temperature is increased from T1 to T3, the optical liquid with a volume of V5 exhibits a contact angle decrease from θ5 to θ7.

[0013] Figures 2A to 2G Depicts the shape and size control of a lens using liquid molding techniques, where Figure 2A Plotted are the contact angle and dimensions (radius and height) of a lens (shown in cross section) conditioned by the wettability of a glass substrate (without physical boundaries) when using a constant liquid volume of approximately 50 nL, Figure 2B Depicted is a lens (cross-sectional view) with a constant 90° contact angle, whose dimensions (radius and height) are controlled by droplet volumes from 5 nL to 800 nL. Figure 2C Plotted is a comparison of the measured and theoretically calculated radii of lenses modulated by liquid volume for substrates of varying wettability (indicated by color). The green triangles indicate Figure 2B The same set of measurements shown. The inset shows three representative lenses with contact angles and radii of approximately 50° / 440μm, 75° / 334μm, and 90° / 277μm, respectively. Scale bar 250μm, Figure 2D Depicted is the cross-sectional profile of a hemispherical lens fabricated on a substrate with a circular boundary (i.e., radius of 493 μm), Figure 2E Depicted is the cross-sectional profile of an ellipsoidal lens fabricated on a substrate with an elliptical boundary (i.e., a semi-major axis length of 460 μm and a semi-minor axis length of 360 μm). The shape and size of the lens are shown in the xz (solid colored line) and yz planes (dashed colored line). Figure 2F Depicted is the cross-sectional profile of a spherical lens (volume ~50 nL) fabricated on a glass substrate with the same chemical wettability treatment but with additional thermal control. As the temperature increases, the contact angle of the resulting lens decreases while the radius increases, Figure 2G Depicted is a study of the shrinkage effect (in terms of contact angle and volume) in a lens by comparing the cross-sectional profile of the lens before (solid colored line) and after (dashed colored line) UV-induced polymerization. According to some embodiments of the present invention, the shrinkage ratio is calculated using (V1-V2) / V1, where V1 and V2 are the volumes of the lens before and after polymerization.

[0014] FIG. 3A to FIG. 3I Depicts a liquid endoscope, where Figure 3A(i) depicts the fabrication of a liquid-like OCT fiber probe. A pre-calculated volume of optical liquid on a glass substrate with improved wetting properties forms a lens with a customized contact angle, shape, and size, which is then polymerized and used as the distal optics of a fiber probe made of single-mode fiber (SMF) and coreless fiber (NCF). Here, the OCT optical axis forms an incident angle θ with respect to the normal axis of the reflective surface of the lens, Figure 3A (ii) Schematic diagram of the OCT endoscope is depicted. The fiber optic probe is enclosed in a hypodermic tube (rigid version) or a torque coil (flexible version) and protected by a glass capillary (rigid version) or a plastic sheath (flexible version). Figure 3A (iii) depicts a magnified view of the distal portion of the endoscope, consisting of an NCF of length L and a hemispherical lens of radius r, and using an incident angle θ. Here, the working distance (WD) refers to the normal distance between the protective sheath surface and the center of the focal plane, Figure 3B The calculated back reflection in the endoscope is plotted as a function of the NCF length L for four representative combinations of lens radius r and incident angle θ. For each combination, as the NCF length L increases from 350 μm to 650 μm, the back reflection decreases by approximately 0.55 dB (black line), 0.33 dB (red line), 0.89 dB (blue line), and 0.41 dB (green line), respectively. Figure 3C Plotted are the calculated back reflections in an endoscope versus lens radius r and incident angle θ using an NCF length of 500 μm. Figures 3D to 3H The red dot in the figure indicates the desired incident angle of 52.5°. Figure 3D shows the color light focal shift, Figure 3E shows the focused spot size, Figure 3F shows the astigmatism ratio, Figure 3G The effective depth of focus (DOF) is shown, and Figure 3H The working distance is shown in Figure 2, which depicts the calculated working distance at different NCF lengths L and lens radii r when the incident angle is 52.5°. Fig. 3I Describes the basis Figures 3D to 3H The optimal design region compiled from the calculation results. The design for manufacturing an endoscope according to some embodiments of the present invention is represented by a red dot.

[0015] Figure 4 Development of a reduced-parts-count fiberoptic endoscope assembly system with passive alignment and in-line quality inspection features according to some embodiments of the present invention is depicted.

[0016] FIG. 5A to FIG. 5I OCT endoscopic features are depicted, including Figure 5A is an image of a magnified view of a rigid endoscope and its distal optics (inset). Figure 5Bis an image of a magnified view of the flexible endoscope and its distal optics (inset). Figure 5C shows the measured 3D profile of a liquid-like lens used in an endoscope, Figure 5D is obtained by nonlinear least squares fitting along four representative radial angles at 0°, 45°, 90°, and 135° ( Figure 5C An image of the 1D surface profile of the lens extended by the measured values ​​of (the dashed line in the figure). Figure 5E The top surface of the lens ( Figure 5C Representative surface roughness measured on the surface of the vehicle (dashed circle in the figure). Fig. 5F Representative surface roughness measured on a planar reflective surface of a lens is shown. Figure 5G A representative focused laser beam profile and focused laser spot measured from a 0.6 mm protective glass capillary of a rigid endoscope are shown (inset). The x-axis represents the distance relative to the focal plane along the emission direction, and 0 μm is the position of the focal plane. The beam diameters in the x and y directions are measured using a beam profiler, and the average diameter is calculated using the weighted equation provided by DataRay, i.e., when x ≥ y, w = 0.83114 × x + 0.16886 × y; or when x < y, w = 0.16886 × x + 0.83114 × y; w is the average diameter, and x and y represent the beam diameters in the x and y directions, respectively. Figure 5H The axial resolution measured along the imaging depth using a representative point spread function is depicted (inset). Here, the imaging depth of 0 μm is the position of zero optical delay between the reference arm and the sample arm. Fig.5I The back reflection spectrum obtained by moving the reflector in the light emitting direction and measured outside the protective sheath of the endoscope is shown. Here, according to some embodiments of the present invention, 0 μm indicates the position of the focal plane.

[0017] FIG. 6A to FIG. 6D shows imaging of the rat esophagus using a flexible endoscope, where Fig. 6A Shown is a cross-sectional view of a reconstructed 3D OCT image of a 36 mm long rat esophagus adjacent to the GEJ. Figure 6B Shown with Fig. 6A Representative 2D OCT images of the cross section framed by green dashed lines. Figure 6C Shows Figure 6B A 3x close-up view of the area marked by the red dashed line in Fig.6D Relevant hematoxylin-eosin (H&E) stained histology is shown. GEJ: gastroesophageal junction, EP: stratified squamous epithelium, LP: lamina propria, MM: muscularis mucosa, SM: submucosa, CM: circular muscle, LM: longitudinal muscle. According to some embodiments of the present invention, the scale bar is 250 μm.

[0018] FIG. 7A to FIG. 7GIn situ imaging of the mouse aorta using a flexible endoscope is shown. Fig. 7A shows the deployment of a flexible endoscope from the left femoral artery to the aortic arch in a mouse. Figure 7B A cross-sectional view of a reconstructed 3D OCT image of a 14.6 mm long mouse thoracic descending aorta is shown. Figure 7C Shows Figure 7B The representative OCT cross section is indicated by the green dashed box in the figure. Fig.7D and Fig. 7E Shows Figure 7C 3x close-up view of the area outlined by the red dashed line in Figure 2 and the associated hematoxylin-eosin (H&E) stained histology. The white arrows point to the deep tissue. Figure 7F and Figure 7G It shows that Figure 7F The depth along line A is shown as Fig.7D An exemplary quantification of the thickness of each thin tissue layer (the distance between the red dashed lines) of a mouse aorta (white arrows in FIG. 1 ). According to some embodiments of the present invention, Figure 7G Shown are the thickness of each aortic layer and its standard deviation measured using 40 A-lines from 10 representative OCT cross-sections, including TI: intima, TM: media, TA: adventitia, EL: elastic lamina, AT: adipose tissue, scale bar 100 μm.

[0019] FIG. 8A to FIG. 8I In vivo imaging of deep regions of the mouse brain using a rigid endoscope is shown. Fig. 8A Shown is the imaging preparation of a mouse brain in which the scalp was incised and two burr holes (approximately 1 mm in diameter) were made in the skull. Figure 8B This is a schematic diagram of deep endoscopy imaging of the mouse brain. Figure 8C A reconstructed volumetric mouse brain image at 5 mm depth is shown. Fig.8D Shows Figure 8C Frontal projection view of the expanded cylindrical OCT volume shown. Fig. 8E Shown with Figure 8C and Fig.8D Related hematoxylin and eosin (H&E) stained histological micrographs of brain samples. FIG. 8F to FIG. 8I Representative cross-sectional images of various mouse brain structures according to some embodiments of the present invention are shown, including the cerebral cortex ( Fig.8F ), corpus callosum ( Figure 8G ), caudate putamen ( Figure 8H ) and ventral striatum ( Figure 8I ), corresponding to Figure 8C Dashed lines in Figure , scale bar is 500 μm.

[0020] FIG. 9A to FIG. 9BThe process of manufacturing a liquid lens according to some embodiments of the present invention is shown, wherein Fig. 9A A flowchart of lens manufacturing is shown, where Fig. 9B The process of manufacturing a liquid-like lens is shown, and the different colors of the glass substrate represent the improvement process of the glass surface properties: yellow indicates that hydroxyl groups (-OH) are exposed on the glass surface during oxygen plasma cleaning; green indicates that fluoride reacts with hydroxyl groups; purple indicates that hydroxyl groups are fully bonded with fluoride and the glass substrate is fully fluorinated.

[0021] FIG. 10A to FIG. 10E The imaging results of the endoscope manufactured at the same time are shown, where the first two images ( Fig. 10A and Fig. 10B ) show 2D cross-sectional images of the mouse brain obtained from rigid endoscopes #1 and #2, respectively. The last three images ( Fig. 10C , Fig. 10D and Fig.10E ) shows cross-sectional images of rat esophagus obtained from #3, #4 and #5 flexible endoscopes, respectively. The imaging results demonstrate that the performance of the endoscopes manufactured at the same time is comparable. According to some embodiments of the present invention, all scale bars are 250 μm.

[0022] Fig.11 A schematic diagram of an endoscopic spectral domain OCT (SD-OCT) system according to some embodiments of the present invention is shown, SLD: superluminescent diode, PC: polarization controller, FC: fiber coupler, RC: reflective collimator, PP: prism pair, RM: reflector, TS: translation stage, RJ: rotary joint.

[0023] Fig.12 The OCT scanning and frontal projection process of the deep part of the mouse brain according to some embodiments of the present invention is shown.

[0024] FIG. 13A to FIG. 13D The long-term stability of the imaging performance of endoscopes manufactured according to some embodiments of the present invention is shown, wherein after 1 month ( Fig.13A )、3 months( Fig. 13B )、6 months( Fig. 13C ) and 12 months ( Fig.13D ) 2D cross-sectional images of the rat esophagus, mouse aorta, and deep part of the mouse brain obtained during the manufacture of the endoscope (from top to bottom). The imaging results demonstrate the long-term stability of the endoscope. All scale bars are 250 μm.

[0025] Fig.14Calibration of the dispensed liquid volume according to some embodiments of the present invention is shown, wherein a series of liquid volumes required by a dispenser are dispensed on a glass substrate to form a liquid lens, and the volumes are measured (measurement accuracy is ±0.05nL), the slope of the fit line is approximately 0.988 and is used to calibrate the required dispensed volume.

[0026] Fig.15 The refractive index profile of NOA81 at room temperature is shown according to some embodiments of the present invention.

[0027] Fig.16 is a schematic diagram of mouse brain processing for histology, wherein the red dots indicate the drilling locations for inserting glass capillaries. According to some embodiments of the present invention, the blue dashed line indicates the transverse direction (the cross section parallel to the xz plane) for brain tissue dissection. DETAILED DESCRIPTION

[0028] Embodiments of the present invention relate to a liquid molding technique for rapid and scalable manufacturing of high-performance OCT endoscopes.

[0029] The terms used herein are for the purpose of describing specific embodiments only and are not intended to limit the present invention. The term "and / or" used herein includes any and all combinations of one or more of the associated listed items. Unless otherwise clearly stated in the context, the singular forms "one" and "the" used herein include plural as well as singular meanings. It should also be understood that the term "comprising" used in this specification is used to illustrate the presence of the described features, steps, operations, elements and / or components, but does not exclude the presence or addition of one or more other features, steps, operations, elements, components and / or combinations thereof.

[0030] Unless otherwise defined, all terms (including technical and scientific terms) used herein have the same meaning as commonly understood by one of ordinary skill in the art to which the present invention belongs. It should also be understood that, unless otherwise explicitly defined, terms defined in commonly used dictionaries should be interpreted as having a meaning consistent with their meaning in the context of the relevant art and the present invention, and will not be interpreted in an idealized or overly formal manner.

[0031] When the term "about" is used in conjunction with a numerical value herein, it should be understood that the value may be within the range of 90% to 110% of the value, that is, the value may be + / -10% of the value. For example, "about 1 kg" means 0.90 kg to 1.1 kg.

[0032] The present invention relates to a method and system based on liquid molding for scalable manufacturing of disposable OCT endoscopes. Fig.16The OCT endoscope and method of manufacturing using liquid molding techniques may be further understood and described in more detail below. It should be understood that the following examples depict exemplary endoscopes and methods of manufacturing, and that variations may be implemented without departing from the inventive concept.

[0033] I. Overview

[0034] In one aspect, free-form lenses can be fabricated by manipulating the minimum energy state of curable optical droplets on substrates with improved wettability and used as focusing optics in OCT endoscopes for volumetric optical biopsy of complex luminal organs, such as Figure 1A to Figure 1B Fabrication can include using a liquid dispenser to dispense precisely controlled droplets onto a substrate and controlling thermal conditions to form a liquid lens, such as Figure 1C to Figure 1G In some embodiments, a piezoelectrically actuated dispenser is used to precisely control the volume of an optical droplet (e.g., NOA 81 from Norland Product Inc. or any suitable liquid). Thermal control is used to heat the dispenser nozzle to about 75° C. with a heater to reduce the viscosity of the liquid from 300 cps to 30 cps, facilitating the dispensing of the optical liquid.

[0035] refer to Figures 1A to 1G , free-form lenses can be fabricated by manipulating the minimum energy state of curable optical droplets on substrates with improved wettability ( Figure 1A ) and used as focusing optics in OCT endoscopes for volumetric optical biopsy of complex luminal organs (see Figure 1B Here, a piezoelectrically actuated dispenser will be developed to precisely control the volume of optical droplets with an accuracy of 0.1 nanoliter. Thermal control will be used to heat the dispenser nozzle to reduce the liquid viscosity, facilitating the dispensing of the optical liquid onto the substrate. The temperature of the liquid on the substrate will be precisely controlled to tune the liquid viscosity and, therefore, the surface shape and size. The substrate will be placed on a 2D translation stage to allow for mass production of free-form lenses of custom shapes and sizes within 10 minutes (see Figure 1A ). Ultraviolet (UV) light will be used to perform the polymerization of the free-form lens. This method achieves this by controlling the wettability (or surface energy, see Figure 1C )、Liquid volume( Figure 1D ) and physical boundaries (i.e., circular or elliptical, Figure 1E and Figure 1F ), which can produce lenses of different shapes and sizes in tens of minutes. In addition to passive methods, lens shape can also be manipulated by active thermal control of optical liquids on substrates (see Figure 1G ). In addition, the liquid-like lens provides a reflective surface with sub-nanometer surface roughness (see Figure 1A), thereby eliminating the additional angle polishing process required by traditional methods based on GRIN fibers and fiber ball lenses.

[0036] refer to Figures 2A to 2G The versatility of this technique was demonstrated by continuously adjusting the contact angle of about 50 nL of optical liquid on a glass substrate (with no physical boundary for the liquid) from about 50° to 110° with an angular accuracy of about 0.5°. This was achieved by changing the wettability of the substrate using a fluorination-based surface wettability improvement method. Once the desired contact angle of the lens (e.g., 90°) was confirmed, the droplet volume was precisely controlled with an accuracy of about 0.1 nL (see Figure 2B ), achieving lens radii between 120 μm and 720 μm with a resolution of about 1 μm, thus verifying the scale invariance of the liquid forming technique. The measured radii (and heights) of lenses fabricated from different liquid volumes on a glass substrate with defined wettability and contact angles correlate closely with the theoretically calculated radii (see Figure 2C ). This indicates that the liquid molding technology has satisfactory controllability in manufacturing spherical and aspherical lenses of predetermined shapes and sizes on substrates without physical boundaries.

[0037] The physical boundaries on the substrate can be used to create lenses with other 3D shapes ( Figure 1E and Figure 1F ). For example, a spherical lens can be fabricated using a 3D printed cylindrical substrate. The radius and contact angle of the liquid lens are initially determined by the wetting properties of the substrate and the volume of the liquid (see Figure 2D ), which is then determined by the physical boundary size and the liquid volume (see Figure 2D solid orange, green and black lines in the figure).

[0038] The fabrication of ellipsoidal lenses was demonstrated using 3D printed ellipsoidal cylindrical substrates. As the volume of liquid was increased, the shape and size of the lens were initially controlled by the wetting properties of the substrate and the volume of liquid (see Figure 2E The blue, purple, and red solid lines on the xz plane and the blue and purple dashed lines on the yz plane) are then mainly constrained by the physical boundaries (see Figure 2E In addition, active thermal control of the lens shape and size has been demonstrated by heating an optical liquid on a substrate with the same wettability. It can be observed that an increase in temperature leads to a decrease in the contact angle and an increase in the radius of the lens of the same volume (see Figure 2F ).

[0039] The wavelength used is about 365nm and the power density is 65mW / cm 2The polymerization of the lens was performed in about 30 minutes under an ultraviolet (UV) lamp (on the lens sample). For the fully polymerized lens, a constant shrinkage ratio of 7.69% in volume was determined, which maintained almost the same contact angle and lens profile as before polymerization (see Figure 2G ). Therefore, the calculated volume of the designed lens was increased by 8.33% to compensate for the shrinkage effect, thereby obtaining the desired shape and size of the polymeric lens.

[0040] Liquid OCT Endoscope

[0041] refer to FIG. 3A to FIG. 3I Liquid molding technology helps to manufacture OCT fiber probes, which are composed of SMF, coreless fiber (NCF) and customized liquid-shaped lens ( Figure 3A (i)). First, the NCF sheet is spliced ​​to the SMF, and then the NCF sheet is coupled to the polymer lens at an incident angle θ by using NOA 81 as an optical adhesive. Subsequently, a hypodermic tube (for rigid version) or a torque coil (for flexible version) is used to protect the OCT probe. The entire probe is then encapsulated in a protective sheath, such as a glass capillary (for rigid version) or a plastic sheath (for flexible version) to form an OCT endoscope ( Figure 3A (ii)). This technology enables the scalable production and manufacture of five endoscopes simultaneously (see Figure 4 ).

[0042] To demonstrate the feasibility of liquid molding technology for imaging performance optimization and aberration correction, a simple hemispherical lens was used to design a typical OCT endoscope operating near 800 nm ( Figure 3A (iii)). The light incident angle was initially optimized by performing a stray light analysis to minimize light back reflections in the endoscope. Total internal reflection was used in cases where the incident angle on the reflective surface of the lens was above the critical angle (i.e., approximately 40.2° at 842 nm). Simulation results showed that the back reflection of the OCT probe is mainly determined by the incident angle and the lens radius, while having relatively little dependence on the NCF length (see Figure 3B ). In general, the larger the lens radius and the angle of incidence, the lower the back reflection of the OCT probe. As a primary example, 52.5° is selected to achieve a back reflection of less than -56 dB at lens radii between 125 μm and 150 μm (see Figure 3C ).

[0043] To further optimize the imaging performance, different combinations of NCF length and lens radius were calculated (see Figures 3D to 3H), the focused spot size (average spot size measured in the x and y directions on the focal plane), the astigmatism ratio (ratio of the spot sizes measured in the x and y directions on the focal plane), the effective DOF, and the working distance (WD). The simulation results are summarized to obtain the optimal design area (see Fig. 3I ), which optimal design region provides optimal imaging performance, such as a chromatic focal shift of less than 6μm, a focused spot size (i.e., lateral resolution) of less than 6μm, an astigmatism ratio between 0.9% and 1.1%, an effective DOF greater than 150μm, and a WD between 200μm and 300μm. A design was used that involved using a 500μm long NCF, a lens with a radius of 140μm, and an incident angle of 52.5° to create a liquid-like endoscope. This approach achieved achromatic performance with a minimum focal shift of approximately 5.4μm, a high lateral resolution of approximately 4.6μm, a low astigmatism ratio of approximately 1.05 on the focal plane, low back reflections of less than -56dB, and appropriate DOF and WD of approximately 197.3μm and 238μm, respectively (see Fig. 3I ).

[0044] Development of a Part Count Reduced Fiberoptic Endoscope Assembly System with Passive Alignment and In-Line Quality Inspection Features

[0045] refer to Figure 4 , achieving a reduced-parts-count design for OCT endoscopes and developing a fiber endoscope assembly system that includes passive alignment and in-line quality inspection features. The OCT endoscope uses a monolithic fiber design that requires only five components, including single-mode fiber (SMF) (780HP, Thorlabs Inc.), coreless fiber (NCF) (FG125LA, Thorlabs Inc.), a custom liquid-like lens, a short section of stainless steel tubing, and a torque coil with a distal side opening ( Figure 4 ). Compared with conventional OCT endoscopes, the use of distal hypodermic tubes, GRIN lenses, glass spacers, and mirror reflectors are reduced. This part count-reduced endoscope design significantly simplifies the endoscope manufacturing process into 4 steps, including step 1: gluing the stainless steel tube to the SMF and sleeve the SMF in the torque coil with a distal side opening within 5 minutes; step 2: splicing the SMF to the NCF and cutting the NCF into a predetermined length within 5 minutes; step 3: coupling the optical fiber to the polymer free-form lens at an incident angle θ by using an optical adhesive and curing the optical adhesive within 10 minutes; step 4: checking the assembly quality online and sleeve and bond the torque coil within 10 minutes (see Figure 4 ).

[0046] For step 2, a Vytran automated glass processor (GPX3800, Thorlabs Inc.) with an integrated cleaver will be used to perform SMF / NCF splicing and inline NCF cleaving. For step 3, passive alignment features in the assembly system include the use of angled v-grooves to help couple the fiber to the free-form lens at an angle θ, and the use of an integrated OCT module to quickly control the distance of the fiber from the lens. The production of endoscopes can be scaled up by implementing multiple angled v-groove modules in parallel.

[0047] A spectral domain OCT module using SLD as light source and spectrometer as detector will be developed and integrated into the endoscope assembly system for rapid inspection of endoscope quality ( Figure 4 ), including unidirectional throughput (at least 90%), back reflection (less than -55dB), point spread function (i.e., axial resolution), focused spot size (i.e., lateral resolution), and imaging quality was tested on a standard phantom. In addition, using the ranging function, the same OCT module will be used to control the distance between the fiber and the lens during the endoscope assembly process.

[0048] Characteristics of OCT endoscopes

[0049] Using the previously described probe design (see Figure 5A and Figure 5B ) fabricated both rigid and flexible versions of liquid-like OCT endoscopes with a diameter of approximately 0.6 mm (including the protective sheath). Five endoscopes were fabricated simultaneously within 90 minutes with comparable results, demonstrating the scalability of the method (see Figure 4 To illustrate the manufacturing quality and controllability of the liquid molding technique, the surface profile of the distal hemispherical lens was first characterized using a 3D non-contact confocal surface analyzer (MarSurf CM Expert, Mahr Inc.). Since the imageable oblique angle of the analyzer is limited to approximately 45°, only the top 40 μm of the lens was measured ( Figure 5C ). One-dimensional surface profiles fitted at four radial angles (i.e., 0°, 45°, 90°, and 135°) showed that the lens was symmetrically hemispherical with a radius of approximately 140.5 ± 0.5 μm (close to the designed radius of 140 μm), indicating that the lens shape and size can be precisely controlled (see Figure 5D Using a surface analyzer based on white light interferometry (MarSurf WI 50, Mahr Inc.), the surface roughness of the lens on the top curved surface was measured to be 0.84 ± 0.11 nm (see Figure 5E ). This sub-nanometer roughness is caused by the flatness of the liquid-gas interface in the liquid molding technology. At the same time, due to the use of an ultra-flat glass substrate, the surface roughness on the flat reflective surface of the lens is 0.53±0.11nm (see Fig. 5FLiquid-like lenses with sub-nanometer surface roughness can effectively mitigate unwanted light scattering in the distal focusing optics of OCT endoscopes.

[0050] To further characterize the endoscope, a spectral domain OCT (SD-OCT) system was constructed (see Fig.11 ). A beam profiler (BladeCam2-XHR, DataRay Inc., Figure 5G ) The diameter of the OCT laser beam leaving a protective sheath (e.g., a glass capillary for a rigid endoscope) is measured in both the x and y directions. The smallest focused spot is about 240 μm from the outer sheath surface, and the spot sizes in the x and y directions are approximately 4.5 μm and 4.3 μm, respectively (the average diameter is 4.5 μm, as shown in Figure 2). Figure 5G ), indicating a low astigmatism ratio of 1.05 at the focal plane. At a working distance of 238μm, these measurements are in good agreement with the simulated focused spot size of 4.6μm. Furthermore, the effective DOF measured by the average beam diameter is approximately 200μm over the depth range where the beam diameter is less than twice the focused spot size, as measured by a polynomial fit. Furthermore, based on the observation that the axial resolution varies by less than 5% along the 1mm imaging depth of approximately 2.43μm (see Figure 5H ) and the nearly constant back reflection spectrum measured by moving the reflector along the luminous direction (see Fig.5I ) verified the achromatism of the endoscope. These results demonstrate the ultra-high resolution of the liquid-like OCT endoscope.

[0051] Super-resolution imaging of luminal organs

[0052] refer to FIG. 6A to FIG. 6D , flexible endoscopes have advantages in mechanical flexibility and ultra-high resolution. It can pass through narrow lumens, such as the narrow part of blood vessels, and smoothly scan tiny luminal organs, such as the esophagus of infants. This endoscope is able to detect fine structures and subtle pathological changes in diseased tissues in the body. In this study, the esophagus of a rat was imaged to evaluate the imaging performance of the endoscope. The probe initially passed through the rat's mouth, passed through the pharynx, passed through the narrow upper esophageal sphincter (a narrow luminal structure that facilitates swallowing and reduces food reflux into the pharynx), and finally reached the gastroesophageal junction (GEJ). 3D volume imaging was performed at a speed of 10 frames / second on a 36mm long esophagus. The adjacent frame interval (i.e., the number of pitches) of 20μm was used to control the pullback speed of the endoscope.

[0053] The reconstructed 3D image shows the GEJ portion of the rat esophagus (see Fig. 6A Representative OCT cross-sections clearly depict the layered microarchitecture of the esophagus near the GEJ (see Figure 6B). The fine layered structure of the esophagus is clearly observed in the magnified view, including the stratified squamous epithelium (EP), lamina propria (LP), muscularis mucosae (MM), submucosa (SM), circular muscle (CM), and longitudinal muscle (LM) (see Figure 6C The microstructure of the esophagus observed on OCT images is consistent with the corresponding hematoxylin-eosin (H&E) stained histological micrographs (see Fig.6D ).

[0054] In situ imaging of complex internal organs

[0055] Currently, accurate assessment of high-risk arterial diseases such as atherosclerosis in small vessels remains challenging due to their narrow lumen, highly complex network, and widespread distribution. Therefore, a flexible endoscope that can perform minimally invasive and ultra-high-resolution imaging in small vessels is highly desirable. To evaluate the function of the endoscope in blood vessels, in situ imaging of the descending aorta was performed in a normal mouse model.

[0056] refer to FIG. 7A to FIG. 7G Prior to imaging, mice were first euthanized by administering an overdose of ketamine and xylazine. The mouse heart and connecting vessels were perfused with phosphate-buffered saline using a 27-gauge needle inserted into the apex of the left ventricle. This perfusion process depleted the aorta of blood, thereby preventing any interference from highly scattering red blood cells during OCT imaging. Subsequently, an endoscope was inserted through the left femoral artery. This endoscope was passed through the abdominal descending aorta and the thoracic descending aorta, finally reaching the portion close to the aortic arch (see Fig. 7A ).

[0057] A 14.6 mm long descending thoracic aorta section was imaged at 10 frames / s with a frame spacing of 20 μm (see Figure 7B ). The imaged aorta was then excised, fixed, embedded, sliced ​​into 10 μm thick sections, and stained with H&E. As shown in the OCT cross-sections, magnified views, and corresponding histological micrographs, the layered microstructure of the mouse aorta, including the intima (TI), media (TM), adventitia (TA), and adipose tissue (AT), can be clearly observed (see FIG. 7C to FIG. 7E In addition, multiple elastic plates (EL, high scattering) mixed with smooth muscle sheets were seen in the TM layer.

[0058] With the help of ultra-high-resolution imaging of the endoscope, the microstructure of the aorta can be clearly described and accurately quantified for in situ assessment of arterial diseases. Preliminary studies have shown that in normal mice, the thickness of the aortic layers of TI, TM, and TA are 11.0 ± 1.2 μm, 69.2 ± 3.4 μm, and 28.2 ± 2.2 μm, respectively (see Figure 7F). Specifically, the TI is the thinnest, innermost layer of an artery or vein and is composed of a single layer of endothelial cells; its thickening and proliferation are considered early signs of atherosclerosis.

[0059] Interstitial imaging deep in the brain in vivo

[0060] refer to FIG. 8A to FIG. 8I The small size of the rigid endoscope can extend the limited imaging depth of OCT and perform high-resolution, volumetric interstitial imaging of solid organs. This helps to understand and evaluate chronic diseases such as deep brain tumors, ischemic stroke, and epilepsy while minimizing the risk of bleeding and other trauma caused by probe insertion.

[0061] To evaluate the functionality of the rigid endoscope, in vivo deep brain imaging was performed on the mouse brain. After an incision was made in the scalp, two burr holes were drilled on each side of the skull (see Fig. 8A ). The endoscope is then inserted deep into the brain through the burr hole, following an insertion trajectory perpendicular to the brain surface (see Figure 8B ). A 5 mm long (in the z direction) cylindrical deep brain volume was imaged in 50 seconds at a rate of 10 frames / second. Due to the ultra-high resolution of the endoscope, mouse brain structures including the cerebral cortex, corpus callosum, caudate putamen, and ventral striatum can be clearly observed on the 3D volumetric images (see Figure 8C ). Frontal projection views generated by summing the unfolded cylindrical brain volumes along the imaging depth showed a distinct laminar brain structure in mice, which was also verified in histological micrographs, demonstrating good correlation between OCT representations and tissue morphology (see FIG. 8D to FIG. 8E and Fig.12 Representative OCT cross-sections acquired at different depths show detailed morphological features of each mouse brain structure (see FIG. 8F to FIG. 8I ). Specifically, the bundle structure of striatopallidal fibers in the caudate putamen was clearly observed on the OCT images (see Figure 8C , Fig.8D and Figure 8H ).

[0062] discuss

[0063] An OCT endoscope with high resolution and large DOF is a must for accurate imaging of subtle lesions within tissues. To this end, the endoscope requires a properly designed lens. However, it is difficult to precisely customize the lens using fiber melting technology. To overcome this limitation, a liquid molding technique is provided. This method enables precise customization of the shape and size of a droplet on a substrate, thereby producing a free-form lens with an ultra-small form factor, corrected aberrations, and desired imaging performance. These features can be achieved by conveniently improving the wettability of the substrate, controlling the liquid volume, and exploiting physical constraints on the substrate. Compared with 3D printing methods, this technology does not require expensive high-end machines and is easy to scale up. In addition, the liquid molding technique can produce customized lenses with sub-nanometer surface roughness (see Figure 5), which is significantly better than the roughness obtained using two-photon 3D printing (approximately 10nm to 200nm).

[0064] Liquid molding technology provides a new approach for manufacturing both high-performance and low-cost OCT endoscopes. The manufacturing process of the endoscope involves only standard and common fiber processing, such as splicing and cleaving, and simple gluing of a custom lens to the tip of the fiber probe (see Figure 4 ). These processes can be streamlined to allow for mass production. This approach eliminates the need for the time-consuming angle polishing process required by conventional approaches based on GRIN fibers and fiber-optic ball lenses. Since the reliance on human expertise is minimized, the use of this approach can significantly reduce manufacturing time and costs and increase production yields. In addition, longitudinal studies have shown that the fabricated endoscopes maintain their imaging performance over a long period of time (see FIG. 13A to FIG. 13D ). Therefore, the liquid-like endoscope can be used as a low-cost disposable OCT catheter for translation.

[0065] Liquid-like OCT endoscopes can be adapted to different clinical applications, such as vessels of different sizes, while maintaining high imaging performance. In principle, the form factor of endoscopes manufactured using liquid molding techniques can be further minimized by using thinner hypodermic tubes or torque coils and smaller protective sheaths throughout the probe. The imaging performance of small-sized endoscopes can be optimized by customizing smaller lenses with appropriate back reflection, achromatism, astigmatism ratio, resolution, and DOF (see Figure 3). Similarly, by manufacturing appropriately designed lenses, the form factor of the endoscope can be increased to image larger lumens (e.g., lumens with diameters greater than 2 mm). In contrast, manufacturing fiber-optic ball lens-based microprobes to image lumens greater than 2 mm would be suboptimal, as microprobes with longer working distances tend to result in decreased lateral resolution and, more importantly, increased longitudinal focal shift.

[0066] Although the use of liquid molding technology to make an 800nm ​​OCT endoscope is a representative example, this technology is not limited to this wavelength. The versatility of liquid molding technology enables the manufacture of OCT endoscopes that work at different other wavelengths. For example, the 1,300nm range can be adapted, which is common in most existing cardiovascular OCT imaging systems. In addition, it is possible to work in the visible light range and the 1,700nm range.

[0067] method

[0068] Droplet generation and characterization

[0069] A piezoelectrically actuated dispenser (SA306, Sans Inc.) was used for droplet / lens generation. This technology has been reported in previous studies and is widely used in microarray printing, tissue engineering, and functional material fabrication. To consider the system dispensing accuracy, the volume of liquid dispensed on the substrate was first calibrated ( Fig.14 ). A series of liquid volumes required by the dispenser are dispensed on a glass substrate to form a liquid lens; the contact angle, size, and volume of the lens are then measured at room temperature 25°C using a droplet analysis system (OCA 25, Dataphysics Instruments GmbH) and analyzed using SCA 20 software (DataPhysics Instruments GmbH). After calibration, the volume of the liquid lens can be controlled with an accuracy of approximately 0.1 nL. The contact angle measurement accuracy is ±0.1°, the length measurement accuracy is ±0.5 μm, and the volume measurement accuracy is ±0.05 nL.

[0070] For polymeric lenses, the contact angle, size, and volume were characterized using the same methods as for liquid lenses, while the lens profile was measured using a confocal profilometer (MarSurf CM Expert, Mahr Inc.) and its surface roughness was characterized using a white light interferometry-based profilometer (MarSurf WI 50, Mahr Inc.).

[0071] Improved surface wettability of glass substrates

[0072] The glass substrates (S2006A1, Ossila) used in the study provided an ultra-polished surface with a roughness of about 1-nm. To improve the surface wettability, the glass substrates were first treated in an oxygen plasma bath for 10 minutes. Then, the substrates were placed in a Petri dish and soaked in a mixture of fluoride (volume: 10 μL to 20 μL) and solvent (volume: 10 mL). The Petri dish was sealed and placed in a fume hood at room temperature for 4 to 16 hours to obtain the desired surface wettability and contact angle on the substrate (see Table 1). Afterwards, the glass substrates were removed and thoroughly rinsed with anhydrous ethanol before use.

[0073] Table 1: Six groups of glass substrates with different surface wettability improvement parameters

[0074] Glass substrate set Processing time[a] Fluoride Volume Contact angle Glass substrate 1 0 hours 0μL ～50° Glass substrate 2 4 hours 10μL ～67° Glass substrate 3 6 hours 10μL ～75° Glass substrate 4 8 hours 10μL ～85° Glass substrate 5 12 hours 10μL ～90° Glass substrate 6 16 hours 20μL ～110°

[0075] [a] Treatment time indicates the time the sample was immersed in the fluoride solution.

[0076] Fabrication of cylindrical substrates and improvement of surface wettability

[0077] A stereolithography 3D printer (S300, nanoArch) was used to fabricate cylindrical substrates with a height of approximately 400 μm and circular or elliptical boundaries. Polyethylene glycol diacrylate (PEGDA) was used for 3D printing.

[0078] To improve the surface wettability, the cylindrical substrate was first treated in an oxygen plasma bath for 10 minutes. Then, it was placed in a Petri dish so that the top surface of the cylinder was immersed in 10 μL of fluoride. The Petri dish was sealed with Kapton tape and placed in a constant temperature oven with a baking temperature of 100 ° C for 4 to 8 hours to obtain the desired surface wettability and contact angle on the substrate (see Table 2). After that, the cylindrical substrate was removed and thoroughly rinsed with anhydrous ethanol before use.

[0079] Table 2: Two groups of cylindrical substrates with different surface wettability improvement parameters

[0080]

[0081]

[0082] [a] Treatment time indicates the time the sample was baked in the oven for fluorination.

[0083] [b] Contact angle measured when the lens is not constrained by physical boundaries.

[0084] Liquid lens manufacturing

[0085] The process of manufacturing lenses using liquid molding technology is as follows Fig. 8A and Figure 8B As shown. Specifically, in this study, NOA 81 was selected relative to other optical liquids. NOA 81 liquid was first degassed in a vacuum chamber (98 kPa vacuum for 10 minutes) to eliminate any potential microbubbles. Then, a piezoelectrically actuated dispenser (SA306, Sans Inc.) was used to dispense a calculated volume of liquid on a glass substrate or a cylindrical substrate / elliptical cylindrical substrate with improved wettability. The desired size or shape of the lens is obtained by precisely controlling the liquid volume, wettability, and physical boundaries of the substrate.

[0086] The liquid lens on the substrate was then degassed again in a vacuum chamber (98 kPa vacuum for 10 minutes). Finally, the liquid lens was polymerized by irradiation with a UV lamp for 30 minutes to ensure complete polymerization, which usually only takes 20 minutes. The UV lamp has a central wavelength of about 365 nm and provides 65 mW / cm on the lens sample. 2 It should be noted that during the lens manufacturing process, the shrinkage effect caused by the polymerization of the optical liquid is taken into account and pre-compensated in the volume calculation (about 7.69%, see Figure 2G ). For the endoscope demonstrated in this study, a volume of approximately 6.2 nL of lens liquid was dispensed on a substrate to produce a hemispherical lens with a radius of approximately 140 μm and a contact angle of approximately 89.8°.

[0087] Zemax Simulation

[0088] OpticStudio (v17, Zemax LLC) was used to design and optimize the liquid-like endoscope. The refractive index profiles and material dispersion of silica (NCF) and NOA 81 were considered in the simulation (see Fig.15 ). First, the back reflections were calculated for different incident angles, lens radii, and NCF lengths using stray light analysis in non-sequential mode. Then, ray tracing simulations of the endoscope were performed in hybrid sequential / non-sequential mode. By considering a single-mode fiber with a numerical aperture of 0.13, the chromatic focal shift, focused spot size, astigmatism ratio, effective DOF, and working distance were calculated for different lens radii and NCF lengths.

[0089] Animal studies and histological correlation

[0090] The rat and mouse OCT endoscopic imaging protocols were approved by the Laboratory Animal Services Center of the Chinese University of Hong Kong.

[0091] For imaging of rat esophagus (n=4, Sprague-Dawley rats) and mouse aorta (n=4, nude mice), animals were euthanized by overdose of ketamine (100 mg / kg) and xylazine (16 mg / kg) prior to OCT imaging. A flexible endoscope was first placed near the GEJ portion of the rat and the aortic arch of the mouse. OCT pullback imaging was then performed at 10 frames / second. The endoscopic probe was retracted after imaging, while the plastic sheath was left in the lumen for imaging tissue alignment. The imaged esophagus and aorta were collected and fixed in formalin overnight together with the plastic sheath and then sent for histological processing. Standard H&E slides were obtained and correlated with the OCT imaging results.

[0092] For deep brain imaging (n = 4, nude mice), mice were first anesthetized by intraperitoneal injection of ketamine (100 mg / kg) and xylazine (16 mg / kg), and anesthesia was further maintained by inhalation of 2% isoflurane and medical oxygen. Drill holes (about 1 mm in diameter) were made on both sides of the mouse skull to allow the deployment of a rigid endoscope (see Fig. 8A ). The drilling location was chosen to avoid major blood vessels. Prior to insertion, a small hole was inserted into the pia mater using a thin needle (approximately 300 μm in diameter). The endoscope was then inserted through the drill hole at a low speed of approximately 10 μm / s into the mouse brain. Immediately after imaging, the mouse was sacrificed and its brain removed. The glass capillary was inserted back into the brain tissue along the same imaging trajectory to help record the imaged tissue. The brain tissue and glass capillaries were then placed together in formalin for 48 hours. After fixation, the brain tissue was divided into two parts (see Fig.16 ) for further histological processing. Standard H&E slides were obtained and correlated with en face OCT images.

[0093] Lens shrinkage before and after polymerization

[0094] After complete polymerization, the liquid lens shrinks at a constant rate, maintaining the contact angle and shape. To study the shrinkage ratio of the NOA 81-based lens, a 365 nm UV lamp was used to provide 65 mW / cm 2 The power density (on the lens sample) was 2.5 % and 1.3 % respectively. The lens volume before polymerization (V1) and the lens volume after polymerization (V2) were measured at room temperature of 25°C using a droplet analysis system (OCA 25, Dataphysics Instruments GmbH). As shown in Table 3 below, it was found that the average volume shrinkage ratio (defined as ) is about 7.69% and the standard deviation is 0.39%.

[0095] Table 3: Lens volume changes before and after polymerization.

[0096]

[0097]

[0098] Therefore, an 8.33% increase in the calculated volume of the designed lens was used to compensate for the shrinkage effect, thereby helping to obtain the desired shape and size of the polymeric lens. For the lens used in the endoscope, the dispensed liquid volume was approximately 6.2 nL to obtain a hemispherical lens with a radius of 140 μm and a lens volume of approximately 5.7 nL.

[0099] Characteristics and imaging results of the simultaneously fabricated liquid-like endoscope

[0100] Five endoscopes were manufactured simultaneously, including two rigid endoscopes (#1 and #2) and three flexible endoscopes (#3, #4, and #5). These endoscopes were characterized with similar results (see Table 4 below) and tested with OCT imaging (see FIG. 10A to FIG. 10E ), with comparable image quality, demonstrating the scalability of liquid molding technology for endoscope manufacturing.

[0101] Table 4: Characteristics of the liquid-like endoscopes fabricated simultaneously.

[0102] Characteristic parameters #1* #2 #3** #4 #5 x Focus spot size 4.5μm 4.6μm 4.5μm 4.7μm 4.5μm y Focus spot size 4.3μm 4.4μm 4.3μm 4.5μm 4.2μm Average focused spot size[a] 4.5μm 4.6μm 4.5μm 4.7μm 4.4μm Astigmatism ratio 1.05 1.05 1.05 1.04 1.07 Effective DOF 200μm 202μm 198μm 204μm 196μm Working distance 240μm 235μm 241μm 237μm 243μm Average axial resolution [b] 2.43μm 2.52μm 2.43μm 2.45μm 2.51μm Axial resolution variation [c] 4.6％ 4.7％ 4.6％ 5.0％ 4.8％ Average spectral change [d] 0.0136 0.0141 0.0138 0.1315 0.0145

[0103] *Reported for rigid endoscopes.

[0104] **Flexible endoscope reported.

[0105] [a] When x ≥ y, the average focused spot size = 0.83114 × x + 0.16886 × y; when x < y, the average focused spot size = 0.16886 × x + 0.83114 × y, where x and y represent the beam diameters in the x and y directions, respectively.

[0106] [bc] The axial resolution is measured every 100 μm along the imaging depth from 100 μm to 1000 μm, and the average axial resolution and axial resolution variation can be calculated.

[0107] [d] The mean spectral variation (MSV) is calculated by MSV=MEAN(STD(S1, S2,…, Si)), where Si is a 2048×1 vector containing normalized spectral data, MEAN is the average operation, and STD represents the standard deviation.

[0108] Ultra-high resolution endoscopic SD-OCT system

[0109] To characterize the performance of the endoscope, a homemade endoscopic spectral domain OCT (SD-OCT) system was constructed (see Fig.11). The custom SD-OCT system used a superluminescent diode source (MT-850-HP, Superlum Inc.) with a 3 dB bandwidth of 160 nm and a central wavelength of approximately 842 nm. A 50:50 fiber coupler (TW850R5A2, Thorlabs Inc.) was used to split the light into the reference arm and the sample arm. A reflective collimator (RC02APC-P01, Thorlabs Inc.) was used to collimate the beam in the reference arm. A pair of N-SF11 prisms (Edmund Inc.) was inserted between the reflective collimator and the reflector (PF05-03-P01, Thorlabs Inc.) to compensate for the dispersion imbalance between the reference arm and the sample arm. A homemade rotary joint was installed on a linear translation stage (X-LSM150A, Zaber Technologies) to rotate and pull back the imaging probe to obtain a three-dimensional volumetric image. The OCT light reflected from the reference arm and the sample arm interferes with each other and is collected using a spectrometer (Cobra-S 800, Wasatch Photonics Inc.) at a high line scan rate of up to 250 kHz. To manage polarization mode dispersion (PMD), two polarization controllers (FPC030, Thorlabs Inc.) are used. The imaging depth of the system is about 1.04 mm.

[0110] Selection of optical liquids for lens manufacturing

[0111] Six representative optical liquids including NOA 60, NOA 61, NOA 63, NOA 65, NOA 68 and NOA 81 (Norland Products Inc.) were considered for lens fabrication (see Table 5). NOA 81 was selected because it has (1) fast curing characteristics (at 65 mW / cm 2 (1) UV light irradiation at a power density of 20 minutes for complete polymerization); (2) good temperature resistance (can withstand -150°C to 125°C after polymerization); (3) low viscosity and easy distribution; (4) relatively high elastic modulus, making it tough and not easy to deform; (5) relatively high transmittance near 800nm ​​(up to 96%).

[0112] Table 5: Comparison of optical fluids

[0113]

[0114]

[0115] [a]-[e]These data are from Norland Product Inc.

[0116] Comparison with existing manufacturing methods and commercial products

[0117] Currently, there are three methods (i.e., traditional methods) to manufacture disposable OCT endoscopes: (1) a gradient refractive index (GRIN) lens / optical fiber-based method; (2) a fiber optic ball lens-based method; and (3) a single-photon or two-photon 3D printing-based method (see Table 6).

[0118] GRIN lens / fiber-based approaches use commercially available GRIN lenses and optical fibers to build OCT endoscopes. However, the limited choice of GRIN lenses and GRIN fibers restricts the optimization of imaging performance. This approach involves complex discrete cross-section assembly and requires precise and time-consuming optical alignment. In addition, the use of GRIN lenses / fibers introduces strong chromatic and spherical aberrations in the near-infrared and visible light ranges, affecting the axial and lateral resolution of OCT endoscopes. Using gradient-index optical fibers, a polishing process is required to fabricate a reflector at the tip of the optical fiber for beam redirection. This polishing process is expensive and time-consuming, and the resulting reflectors typically have undesirable surface roughness.

[0119] (1) The fiber optic ball lens-based method uses an electric arc or filament to melt the optical fiber and produce a spherical lens at the tip of the optical fiber (i.e., fiber melting technology). This method has been shown to be able to be used to manufacture monolithic OCT endoscopes with achromatic performance. However, in this method, an angle polishing process is required to produce a reflective surface on the spherical lens for beam redirection. This polishing process is expensive and time-consuming, and the resulting reflector usually has an undesirable surface roughness. Fiber melting technology also lacks sufficient controllability to customize the spherical lens and optimize its imaging performance.

[0120] (2) Single-photon or two-photon 3D printing methods are able to produce free-form optics directly on the tip of an optical fiber to fabricate a monolithic OCT endoscope. However, the optical surface roughness of the printed optics is not ideal, ranging between 10 nm and 200 nm, resulting in undesirable light scattering, which may degrade OCT imaging performance. Considering the additive manufacturing characteristics and expensive 3D printers, this approach is costly and not scalable.

[0121] Unlike conventional methods, this method (i.e., liquid molding-based method) uses liquid molding technology to manufacture high-performance OCT endoscopes (i.e., liquid-like OCT endoscopes) in less than 1.5 hours. This method enables (1) mass production of free-form optical devices with sub-nanometer surface roughness and customized imaging performance in less than 30 minutes, and (2) rapid automated assembly of OCT endoscopes with monolithic design and customized specifications in less than 60 minutes. The liquid molding technology-based method provides excellent controllability and sufficient flexibility to manufacture customized free-form optical devices. The automated manufacturing system eliminates the need for lens polishing and high-precision optical alignment.

[0122] Table 6: Comparison of traditional methods and liquid molding-based manufacturing methods

[0123]

[0124]

[0125] Table 7: Performance and price comparison of commercial endoscopes and liquid endoscopes for cardiovascular OCT systems

[0126]

[0127]

[0128] Table 8: Manufacturing cost of liquid OCT endoscope

[0129] Components cost Fiber Optic Patch Cables $10 Torque coil $50 Optical Liquids $1 Protective case $4 Other consumables and processing parts $5 Total $70

[0130] Advantages of Disposable Cardiovascular OCT Endoscopes

[0131] Disposable OCT endoscopes (i.e., liquid-based OCT endoscopes) are designed to provide a low-cost, high-performance alternative to current cardiovascular OCT market participants. This has several advantages for patients and healthcare providers:

[0132] a. Low adoption cost, improved patient accessibility and benefits: Mass production of liquid-based OCT endoscopes can significantly reduce the cost of OCT endoscopes in clinical practice and provide OCT with competitive advantages over IVUS in terms of imaging performance and cost.

[0133] b. Improve patient safety and prognosis: Disposable endoscopes can help minimize the risk of cross-contamination and infection associated with reusable endoscopes, thereby improving patient safety and reducing the likelihood of nosocomial infections. In addition, customizing disposable OCT endoscopes for individual patients, such as adjusting the catheter size to accommodate different blood vessel sizes, and adjusting the resolution capability and imaging depth within the tissue, can better meet diagnostic and interventional needs, thereby improving patient prognosis.

[0134] In one embodiment, a method for scalably producing free-form optical lenses based on liquid molding technology is provided, the method comprising: forming a liquid-like lens by dispensing a curable optical liquid on a substrate and curing, wherein the surface of the substrate is pretreated to have a predetermined wettability in a predesigned area, wherein the curable optical liquid is dispensed in the predesigned area on the substrate to form a liquid polymer lens, and wherein the liquid polymer lens is dispensed in the predesigned area on the substrate to have a predetermined size and a predetermined shape; and polymerizing the liquid polymer to form the liquid-like lens.

[0135] In one embodiment, the polymerization includes UV light irradiation and heating.

[0136] In one embodiment, the size and the shape of the liquid lens are free-form, and the method further comprises: actively configuring the pre-designed area with specific wettability, and controlling the volume of the curable optical liquid filling the pre-designed area.

[0137] In one embodiment, the actively configuring the pre-designed area includes performing a surface wettability improvement method, which includes a passive chemical treatment method or an active improvement method, which includes thermal control and electromagnetic field control of surface wettability.

[0138] In one embodiment, the liquid lens has a sub-nanometer surface roughness.

[0139] In one embodiment, the production of the liquid lens is performed simultaneously with the production of multiple liquid lenses of different shapes and sizes without increasing production time.

[0140] In one embodiment, a high-performance optical coherence tomography (OCT) endoscope system manufactured based on liquid molding technology is provided, the system comprising: an OCT imaging probe, the OCT imaging probe comprising: a single-mode optical fiber; a beam transmission element spliced ​​to the single-mode optical fiber; and an aberration-corrected liquid lens manufactured using liquid molding technology, wherein the liquid lens is configured to have a predetermined size, a predetermined shape, and is bonded to the end of the beam transmission element with a predetermined length so as to reduce the chromatic aberration, spherical aberration and astigmatism of the OCT imaging probe and obtain high axial and lateral resolution, wherein the liquid lens is coupled to the end of the beam transmission element at a predetermined alignment angle for beam redirection and focusing, and wherein the liquid lens is coupled to the end of the beam transmission element, the liquid lens is manufactured using an optical liquid and then polymerized to form the lens; and a protective metal shell, the OCT imaging probe having a predetermined size is mounted in the protective metal shell and is protected by a transparent shell to define a high-performance OCT endoscope, wherein the protective metal shell has a pre-cut opening on its cylindrical surface as a beam passage window.

[0141] In one embodiment, the beam transmission element comprises a coreless optical fiber or a multimode optical fiber.

[0142] In one embodiment, the polymerization includes any one of: UV light irradiation, drying, and heating.

[0143] In one embodiment, the distal optics of the liquid OCT lens has sub-nanometer surface roughness to reduce strong scattering at short wavelengths and improve image quality.

[0144] In one embodiment, the liquid lens is configured to have high transmittance and low back reflection over a wide spectral range. High transmittance is expressed as a large percentage of the optical power transmitted through the lens (e.g., a percentage greater than 95%). Low back reflection is a small portion of the optical power reflected back by the lens (e.g., a value less than -55 decibels). The wide spectral range is expressed as a large bandwidth of color light, for example, in the range of 400nm to 700nm, or in the range of 650nm to 950nm, or in the range of 1265nm to 1380nm.

[0145] In one embodiment, the broad spectral range includes the range from visible light to near infrared light.

[0146] In one embodiment, the system is configured to manufacture multiple liquid OCT imaging probes simultaneously to achieve batch manufacturing.

[0147] In one embodiment, a method for scalably producing free-form optical reflectors based on liquid molding technology is provided, the method comprising: manufacturing the reflector by dispensing a predetermined shape of a curable liquid in a container and curing the liquid to define the reflector, wherein the container has a predetermined size and a predetermined boundary; wherein the curable liquid is dispensed according to a precalculated volume and dispensed into the container by a high-precision dispenser, wherein the free-form shape of the upper surface of the dispensed curable liquid in the container is determined by the volume of the liquid and the boundary of the container, and wherein the body of the reflector is defined by the cured liquid; and coating a highly reflective metal or dielectric layer on the cured liquid according to the predetermined size and the predetermined boundary so as to define the outer reflective surface of the reflector.

[0148] In one embodiment, the curing includes polymerization, which includes any one of: UV light irradiation, drying, and heating.

[0149] In one embodiment, the polymerized liquid-like mirror has a sub-nanometer surface roughness.

[0150] In one embodiment, the liquid-like reflector is detachable from or attached to the container.

[0151] In one embodiment, a high-performance optical coherence tomography (OCT) endoscope system manufactured based on liquid molding technology includes: a single-mode optical fiber; a beam transmission element spliced ​​to the single-mode optical fiber for transmitting a beam through the single-mode optical fiber; and an aberration-corrected reflector manufactured using the liquid molding technology; wherein the beam transmission element transmits the beam to the reflector; wherein the aberration-corrected liquid-like reflector is configured to have a desired free-form reflective surface for beam redirection and focusing, wherein the reflector and the beam transmission element are located in a protective metal housing and protected by a transparent housing, thereby forming the high-performance OCT imaging endoscope, and wherein the protective metal housing has an opening pre-cut on its cylindrical surface as a beam passage window.

[0152] In one embodiment, the beam transmission element includes any one of a coreless optical fiber, a multimode optical fiber, and a fiber optic ball lens.

[0153] In one embodiment, the reflector has a free-form reflective surface formed by liquid molding, and the free-form reflective surface is disposed at a predetermined tilt angle to redirect and focus the light beam.

[0154] In one embodiment, the tilt angle is at least partially determined by the bounding shape of the 3D printed container in which the liquid is deposited.

[0155] In one embodiment, the beam transmission element and the reflector are configured to reduce chromatic aberration, spherical aberration and astigmatism of the high performance OCT imaging probe and achieve high resolution.

[0156] In one embodiment, the reflector is configured to have high reflectivity and low back reflection over a wide spectral range.

[0157] In one embodiment, the broad spectral range includes the range from visible light to near infrared light.

[0158] In the foregoing description, the present invention is described with reference to specific embodiments of the present invention, but those skilled in the art will recognize that the present invention is not limited thereto. The various features, embodiments and aspects of the above invention may be used individually or in combination. In addition, without departing from the broader spirit and scope of this specification, the present invention may be used in any number of environments and applications beyond the environment and application described herein. Therefore, the description and the accompanying drawings should be considered to be illustrative rather than restrictive. It should be recognized that, specifically, the terms "including", "comprising" and "having" used herein are intended to be understood as unrestricted technical terms. Any reference to publications, patents or patent applications is incorporated herein by reference in their entirety for all purposes.

[0159] Exemplary Embodiments

[0160] Embodiments of the present invention include but are not limited to the following exemplary embodiments:

[0161] Embodiment 1. A method for scalably producing a free-form optical lens based on liquid molding technology, the method comprising:

[0162] forming a liquid-like lens by dispensing a curable optical liquid on a substrate and curing, wherein a surface of the substrate is pre-treated to have a predetermined wettability in a pre-designed area, wherein the curable optical liquid is dispensed in the pre-designed area on the substrate to form a liquid polymer lens, and wherein the liquid polymer lens is dispensed in the pre-designed area on the substrate to have a predetermined size and a predetermined shape; and

[0163] The liquid polymer lens is polymerized to form the liquid-like lens.

[0164] Embodiment 2. The method of embodiment 1, wherein the polymerization comprises UV light irradiation and heating.

[0165] Embodiment 3. A method according to embodiment 1, wherein the size and shape of the liquid lens are free-form, and the method further comprises: actively configuring the pre-designed area with specific wettability, and controlling the volume of the curable optical liquid filling the pre-designed area.

[0166] Embodiment 4. A method according to embodiment 3, wherein the active configuration of the pre-designed area includes performing a surface wettability improvement method, the surface wettability improvement method includes a passive chemical treatment method or an active improvement method, the active improvement method includes thermal control and electromagnetic field control of surface wettability.

[0167] Embodiment 5. The method according to embodiment 1, wherein the liquid lens has a sub-nanometer surface roughness.

[0168] Embodiment 6. The method according to embodiment 1, wherein the production of the liquid lens is performed simultaneously with the production of multiple liquid lenses of different shapes and sizes without increasing the production time.

[0169] Embodiment 7. A high-performance optical coherence tomography (OCT) endoscope system manufactured based on liquid molding technology, the system comprising:

[0170] OCT imaging probe, the OCT imaging probe comprising:

[0171] Single mode optical fiber;

[0172] a beam delivery element spliced ​​to the single mode optical fiber; and

[0173] an aberration-corrected liquid lens manufactured using a liquid molding technique, wherein the liquid lens is configured to have a predetermined size, a predetermined shape, and is bonded to an end of the beam transmission element with a predetermined length so as to reduce chromatic aberration, spherical aberration, and astigmatism of the OCT imaging probe and obtain high axial and lateral resolution, wherein the liquid lens is coupled to the end of the beam transmission element at a predetermined alignment angle for beam redirection and focusing, and wherein the liquid lens is coupled to the end of the beam transmission element, and the liquid lens is manufactured using an optical liquid and then polymerized to form the lens; and

[0174] A protective metal housing, the OCT imaging probe having a predetermined size is mounted within the protective metal housing and protected by a transparent housing to define a high-performance OCT endoscope, wherein the protective metal housing has a pre-cut opening on its cylindrical surface as a beam passage window.

[0175] Embodiment 8. A system according to embodiment 7, wherein the light beam transmission element comprises a coreless optical fiber or a multimode optical fiber.

[0176] Embodiment 9. The system of embodiment 7, wherein the polymerization comprises any one of: UV light irradiation, drying, and heating.

[0177] Embodiment 10. A system according to embodiment 7, wherein the distal optical device of the liquid OCT lens has sub-nanometer surface roughness to reduce strong scattering of short wavelengths and improve image quality.

[0178] Embodiment 11. The system of embodiment 7, wherein the liquid-like lens is configured to have high transmittance and low back reflection over a wide spectral range.

[0179] Embodiment 12. The system of embodiment 11, wherein the wide spectral range includes a range from visible light to near infrared light.

[0180] Embodiment 13. The system according to embodiment 7, wherein the system is configured to manufacture multiple liquid OCT imaging probes simultaneously to achieve batch manufacturing.

[0181] Embodiment 14. A method for scalably producing free-form optical reflectors based on liquid molding technology, the method comprising:

[0182] Manufacturing a reflector, the reflector being manufactured by dispensing a predetermined shape of a curable liquid in a container and curing the liquid to define the reflector, wherein the container has predetermined dimensions and predetermined boundaries; wherein the curable liquid is dispensed according to a pre-calculated volume and is dispensed into the container by a high-precision dispenser, wherein a free-form shape of an upper surface of the dispensed curable liquid in the container is determined by the volume of the liquid and the container boundaries, and wherein a body of the reflector is defined by the cured liquid; and

[0183] A highly reflective metal or dielectric layer is coated on the solidified liquid according to the predetermined size and the predetermined boundary so as to define an outer reflective surface of the reflector.

[0184] Embodiment 15. The method of embodiment 14, wherein the curing comprises polymerization, the polymerization comprising any one of: UV light irradiation, drying, and heating.

[0185] Embodiment 16. The method of embodiment 14, wherein the polymerized liquid-like mirror has a sub-nanometer surface roughness.

[0186] Embodiment 17. The method of embodiment 14, wherein the liquid-like reflector is detachable from or attached to the container.

[0187] Embodiment 18. A high-performance optical coherence tomography (OCT) endoscope system manufactured based on liquid molding technology, the system comprising:

[0188] Single mode optical fiber;

[0189] a light beam transmission element, spliced ​​to the single-mode optical fiber, for transmitting a light beam through the single-mode optical fiber; and

[0190] an aberration-corrected reflector, manufactured using the liquid molding technology;

[0191] wherein the beam transmission element transmits the beam to the reflector;

[0192] wherein the aberration-corrected liquid-like mirror is configured to have a desired free-form reflective surface for beam redirection and focusing,

[0193] wherein the reflector and the beam transmission element are located in a protective metal housing and protected by a transparent housing, thereby forming the high performance OCT imaging endoscope, and

[0194] The protective metal shell has an opening pre-cut on its cylindrical surface as a light beam passage window.

[0195] Embodiment 19. A system according to embodiment 18, wherein the beam transmission element includes any one of a coreless optical fiber, a multimode optical fiber, and a fiber optic ball lens.

[0196] Embodiment 20. The system of Embodiment 18, wherein the reflector has a free-form reflective surface formed by liquid molding, and the free-form reflective surface is disposed at a predetermined tilt angle to redirect and focus the light beam.

[0197] Embodiment 21. A system according to Embodiment 20, wherein the tilt angle is at least partially determined by the bounding shape of a 3D printed container in which the liquid is deposited.

[0198] Embodiment 22. A system according to embodiment 18, wherein the beam transmission element and the reflector are configured to reduce chromatic aberration, spherical aberration and astigmatism of the high-performance OCT imaging probe and obtain high resolution.

[0199] Embodiment 23. The system of Embodiment 18, wherein the reflector is configured to have high reflectivity and low back reflection over a wide spectral range.

[0200] Embodiment 24. The system of embodiment 23, wherein the wide spectral range includes a range from visible light to near infrared light.

[0201] All patents, patent applications, provisional applications, and publications mentioned or cited herein are incorporated by reference, including all figures and tables, to the extent not inconsistent with the explicit teachings of this specification.

[0202] It should be understood that the examples and embodiments described herein are for illustrative purposes only, and those skilled in the art will make various modifications or changes based on these examples and embodiments, and include them in the spirit and scope of this application and the scope of the appended claims. In addition, any element or limitation of any invention or embodiment disclosed herein may be combined with any and / or all other elements or limitations disclosed herein (alone or in any combination) or any other invention or embodiment thereof, and all such combinations are included in the scope of the present invention without being limited thereto.

Claims

1. A method for scalably producing free-form optical lenses based on liquid molding technology, the method comprising: forming a liquid-like lens by dispensing a curable optical liquid on a substrate and curing, wherein the surface of the substrate is pre-treated to have a predetermined wettability in a pre-designed area, wherein the curable optical liquid is dispensed in the pre-designed area on the substrate to form a liquid polymer lens, and wherein the liquid polymer lens is dispensed in the pre-designed area on the substrate to have a predetermined size and a predetermined shape; as well as The liquid polymer lens is polymerized to form the liquid-like lens.

2. The method of claim 1, wherein the polymerization comprises UV light irradiation and heating.

3. The method of claim 1, wherein the size and shape of the liquid lens is free-form, and the method further comprises: Actively configuring the pre-designed area with specific wettability, and controlling the volume of the curable optical fluid filling the pre-designed area.

4. The method according to claim 3, wherein the active configuration of the pre-designed area includes performing a surface wettability improvement method, the surface wettability improvement method includes a passive chemical treatment method or an active improvement method, the active improvement method includes thermal control and electromagnetic field control of surface wettability. The method of claim 1 , wherein the liquid-like lens has a sub-nanometer surface roughness.

6. The method according to claim 1, wherein the production of the liquid-like lens is performed simultaneously with the production of a plurality of liquid-like lenses of different shapes and sizes without increasing the production time.

7. A high-performance optical coherence tomography (OCT) endoscope system manufactured based on liquid molding technology, the system comprising: An OCT imaging probe, wherein the OCT imaging probe comprises: Single mode optical fiber; a beam delivery element spliced ​​to the single mode optical fiber; and an aberration-corrected liquid lens manufactured using a liquid molding technique, wherein the liquid lens is configured to have a predetermined size, a predetermined shape, and is bonded to an end of the beam transmission element with a predetermined length so as to reduce chromatic aberration, spherical aberration, and astigmatism of the OCT imaging probe and obtain high axial and lateral resolution, wherein the liquid lens is coupled to the end of the beam transmission element at a predetermined alignment angle for beam redirection and focusing, and wherein the liquid lens is coupled to the end of the beam transmission element, and the liquid lens is manufactured using an optical liquid and then polymerized to form the lens; and A protective metal housing, the OCT imaging probe having a predetermined size is mounted within the protective metal housing and protected by a transparent housing to define a high-performance OCT endoscope, wherein the protective metal housing has a pre-cut opening on its cylindrical surface as a beam passage window.

8. The system of claim 7, wherein the beam transmission element comprises a coreless optical fiber or a multimode optical fiber.

9. The system of claim 7, wherein the polymerization comprises any one of: UV light irradiation, drying, and heating.

10. The system of claim 7, wherein the distal optics of the liquid OCT lens has sub-nanometer surface roughness to reduce strong scattering of short wavelengths and improve image quality.

11. The system of claim 7, wherein the liquid-like lens is configured to have high transmittance and low back reflection over a wide spectral range.

12. The system of claim 11, wherein the broad spectral range includes a range from visible light to near infrared light.

13. The system according to claim 7, wherein the system is configured to manufacture a plurality of liquid OCT imaging probes simultaneously to achieve batch manufacturing.

14. A method for scalably producing free-form optical reflectors based on liquid molding technology, the method comprising: Manufacturing a reflector, the reflector being manufactured by dispensing a curable liquid of a predetermined shape in a container and curing the liquid to define the reflector, wherein the container has predetermined dimensions and predetermined boundaries; wherein the curable liquid is dispensed according to a pre-calculated volume and is dispensed into the container by a high-precision dispenser, wherein a free-form shape of an upper surface of the dispensed curable liquid in the container is determined by the volume of the liquid and the container boundaries, and wherein a body of the reflector is defined by the cured liquid; as well as A highly reflective metal or dielectric layer is coated on the solidified liquid according to the predetermined size and the predetermined boundary so as to define an outer reflective surface of the reflector.

15. The method of claim 14, wherein the curing comprises polymerization, the polymerization comprising any one of: UV light irradiation, drying, and heating.

16. The method of claim 14, wherein the polymerized liquid-like mirror has a sub-nanometer surface roughness.

17. The method of claim 14, wherein the liquid-like reflector is detachable from or attached to the container.

18. A high-performance optical coherence tomography (OCT) endoscope system manufactured based on liquid molding technology, the system comprising: Single mode optical fiber; a light beam transmission element, spliced ​​to the single-mode optical fiber, for transmitting a light beam through the single-mode optical fiber; and an aberration-corrected reflector, manufactured using the liquid molding technology; wherein the beam transmission element transmits the beam to the reflector; wherein the aberration-corrected liquid-like mirror is configured to have a desired free-form reflective surface for beam redirection and focusing, wherein the reflector and the beam transmission element are located in a protective metal housing and protected by a transparent housing, thereby forming the high performance OCT imaging endoscope, and The protective metal shell has an opening pre-cut on its cylindrical surface as a light beam passage window.

19. The system of claim 18, wherein the beam transmission element comprises any one of a coreless optical fiber, a multimode optical fiber, and a fiber optic ball lens.

20. The system of claim 18, wherein the reflector has a free-form reflective surface formed by liquid molding, and the free-form reflective surface is disposed at a predetermined tilt angle to redirect and focus the light beam.

21. The system of claim 20, wherein the tilt angle is at least partially determined by a bounding shape of a 3D printed container in which the liquid is deposited.

22. The system of claim 18, wherein the beam transmission element and the mirror are configured to reduce chromatic aberration, spherical aberration, and astigmatism of the high performance OCT imaging probe and achieve high resolution.

23. The system of claim 18, wherein the reflector is configured to have high reflectivity and low back reflection over a wide spectral range.

24. The system of claim 23, wherein the broad spectral range includes a range from visible light to near infrared light.

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