TW202242340A - Optical system and interfernce objective module therof - Google Patents

Abstract

Provided herein are interference objective modules comprising an objective, and an interference module comprising a reference plate disposed apart from the objective to provide a reference arm, a beam splitter to split a source light processed from the objective, and a sample plate to translate the split light from the beam splitter to provide a sample arm, wherein the interference module is configured to make a distance of a focal plane and an interference plane of the interference objective module varied during a measurement, and wherein the focal plane and the interference plane of the interference objective module intersect during the measurement.

Description

Optical system and its interference objective lens module

The invention relates to an optical system and its interference objective lens module. The present application also relates to a method for imaging a sample by the optical system.

An optical system is a combination of lenses, mirrors, and mirrors that constitute the optical part of an optical instrument. In recent years, non-invasive optical systems are a widely used technique, such as optical coherence tomography (OCT), reflection confocal microscopy (RCM), two-photon luminescence microscopy (TPL), etc. There are many types of non-invasive imaging optics. For example, an optical coherence tomography (OCT) system is an optical system using image interference technology, which has been widely used in tissue imaging reconstruction. This interferometric imaging technique enables high-resolution cross-sectional imaging of biological samples. For imaging interferometry, broadband illumination will facilitate axial resolution and produce high-resolution cross-sectional/volume images.

The invention relates to an interference objective lens module and its optical system, which are used to improve the overall image quality of high-resolution OCT images between different tissue types.

The present invention provides an interference objective lens module, which includes an objective lens and an interference module, and the interference module includes a reference plate which is set apart from the objective lens to provide a reference arm, and a source light for taking the source light from the objective lens. A beam splitter for beam splitting, and a sample slide for transmitting the split light from the beam splitter to provide a sample arm, wherein the interference module is constructed so that the focal plane and the interference plane of the interference objective lens module The distance varies during a measurement, and wherein the focal plane and the interference plane of the interference objective lens module intersect during the measurement.

In some aspects, the present application provides an apparatus/system comprising: an illumination module configured to provide a source light to an optical interference module, and the optical interference module converts the source light into a line of light and process light signals; an interference objective lens module disclosed in the case, which is used to process light from the optical interference module and process light signals generated by a sample; a two-dimensional camera, which is constructed to receive an interference signal backscattered by the sample; and a data processing module for processing the interference signal into an image.

In another aspect, this application also provides a method for imaging a sample, which is performed by a device/system comprising the interference objective lens module of the present invention, wherein the interference module disclosed in this application is constructed so that the interference objective lens module The distance between the focal plane and the interference plane of the set is varied during a measurement, and the focal plane and the interference plane of the interference objective lens module are intersected during the measurement.

INCORPORATION BY REFERENCE All publications, patents, and patent applications mentioned in this specification are herein incorporated by reference to the same extent as if each individual publication, patent, or patent application was specifically and individually indicated to be incorporated by reference. incorporated.

Optical interferometry is widely used in science and industry. It is also used in medical fields such as dermatology, ophthalmology or oral health. In medical applications, the refractive index is not always uniform throughout tissue. For example, the stratum corneum and cancerous tissue typically have a higher refractive index than other skin tissues. Therefore, it is not easy to visualize features at cellular level resolution throughout the tissue. The present invention provides an optical system equipped with a specific interference objective lens module to improve the above defects while maintaining high resolution and SNR value so as to observe samples at different depths adjustable.

Combining high numerical aperture optical elements and broadband light sources, OCT can achieve near-equal spatial resolution of about one micron. This feature makes OCT an effective tool for providing cellular-resolution imaging. One problem with this system is that the depth of focus (DOF) is limited. As DOF is limited, a small portion of the OCT cross-sectional (B-scan) image will have good resolution, but most will be blurry. Some methods can solve this problem, including image fusion, Bessel beam generation (Bessel beam generation), dynamic focusing, etc. Most methods require some compromise in spatial resolution (ie, image fusion) or sensitivity (ie, Bessel beam). One way to optimize spatial resolution and sensitivity is to simultaneously move the focal plane and the interference plane during axial scanning; however, there are two problems with this approach. First, it is difficult to maintain the same imaging performance across different tissues because the optical properties of the sample (ie, the refractive index) are usually not known in advance and vary significantly from tissue to tissue. This problem is especially acute in systems with high numerical apertures where the DOF is narrow and where the system is susceptible to differences in sample properties. Another problem is that at least two axial scanning modules are required to be able to move the focal plane and the interference plane without moving the sample (ie, the patient), significantly increasing the cost and complexity of the system.

One of the problems with high-resolution OCT imaging in biological tissue is the mismatch between the focal plane (FP) and the interference plane (IP). In the case of OCT with dynamic focusing (where the focal plane (FP) moves during the axial scan), this problem can in principle be avoided by carefully selecting an immersion fluid with a refractive index (RI) close to that of the sample tissue. However, the refractive index (RI) of biological tissue is always depth-dependent and varies from body part to body part, so a mismatch between the focal plane (FP) and the interference plane (IP) is difficult to avoid. In some cases, this problem reduces the spatial resolution of the imagery. In the case of OCT based on low spatially coherent light sources (i.e., halogen lamps), this will also be more difficult than for systems with spatially coherent light sources (i.e., supercontinuum sources) because out-of-focus signals are less likely to interfere. resulting in a severe decrease in sensitivity.

Methods that have been proposed to solve this problem include using numerical methods for image refocusing, or compensating for this mismatch by using special scanning elements such as objectives and reference modules. The present invention provides a system/method that allows focal plane (FP) and Mismatches between interference planes (IPs) are minimized. With this setup, the system can cover more diverse tissue types and can be extended by changing the number of built-in mismatches.

，且干涉平面（IP）的深度掃描速度為

。若該等掃描速度在掃描過程中是恆定的，則可將錯配表示為：

The following is a simple model of the mismatch between the focal plane (FP) and the interference plane (IP). First define the depth scanning speed of the focal plane (FP) as

, and the depth scan speed of the interference plane (IP) is

. If these scan rates are constant during the scan, the mismatch can be expressed as:

是焦平面（FP）和干涉平面（IP）間的錯配，z是干涉平面（IP）的深度位置，

是前文所述之內建錯配，且

是錯配相對於深度的增加率。在此一簡單模型中（各平面的速度恆定），在

和

皆為零時，即可使整體錯配最小化，且若

和/或

不為零，則它們的符號相反。

is the mismatch between the focal plane (FP) and the interference plane (IP), z is the depth position of the interference plane (IP),

is a built-in mismatch as described earlier, and

is the rate of increase of mismatches with respect to depth. In this simple model (constant velocity in all planes), at

with

When both are zero, the overall mismatch can be minimized, and if

and / or

If not zero, their signs are reversed.

For OCT with only one scanning axis (i.e., scanning a Michelson/Linick type interferometer that moves between the interferometer and the sample, or a Millau type interferometer), the velocity of each plane moving within the sample ( relative to the last plane of the interferometer or the surface of the sample) can be estimated as:

是干涉儀和樣品之間的相對速度，

是干涉儀和樣品之間隔空間（經常填充有浸液）的折射率，而

值是樣品的折射率。就活體內組織成像而言，常見到樣品的平均折射率隨著深度而變化。更確切來說，上層可能具有比下層更高或更低的折射率。例如，表層皮膚由角質層和表皮組成，角質層的平均折射率通常高於表皮。由於

值與深度相依，即使具有恆定的

值，

和

亦仍為深度的函數。

is the relative velocity between the interferometer and the sample,

is the refractive index of the space between the interferometer and the sample (often filled with immersion liquid), while

The value is the refractive index of the sample. For in vivo tissue imaging, it is common to see that the average refractive index of a sample varies with depth. Rather, the upper layer may have a higher or lower refractive index than the lower layer. For example, superficial skin consists of the stratum corneum and the epidermis, and the average refractive index of the stratum corneum is generally higher than that of the epidermis. because

Values are depth dependent, even with a constant

value,

with

Also remains a function of depth.

（亦即，浸液的折射率）和

（內建錯配的數量）的考量點。若

值隨著深度而降低，則

也是如此。在此情況下，

的初始值較佳為正值，如此可將

的整體絕對值最小化，因此，

應被選定為小於樣品表層區域的

值。而且在此例中，

應為負值，以使整體

值最小化。 The following examples are selected

(that is, the refractive index of the immersion liquid) and

(number of built-in mismatches) considerations. like

value decreases with depth, then

is also like this. In this situation,

The initial value of is preferably a positive value, so that the

The overall absolute value of is minimized, therefore,

should be chosen to be smaller than the surface area of the sample

value. And in this example,

should be negative so that the overall

value is minimized.

For being able to solve the foregoing problems, the present invention provides the concrete example of optical system as shown in Figure 1, and it comprises a light source A, is used to provide a source light to optical interference module B; An interference objective lens module C, its processing comes from light in the optical interference module B and process the optical signal generated by a sample; and a detector D, which detects the interference signal from the sample. In addition, a data processing module E may be provided to process the interference signal into an interference image.

The interference objective lens module C includes an objective lens and an interference module. The interference module includes a beamsplitter for separating the source light; a reference slide for providing a reference arm; and a sample slide for processing the sample arm from the sample. Figure 2A shows an exemplary Millau-type interference objective lens module. The Millau type interference objective lens module includes an objective lens 10 and an interference module 20, wherein the interference module 20 includes a reference sheet 21 configured separately from the objective lens 10 to provide a reference arm; a beam splitter 22 is used for light splitting source light processed by the objective lens 10 and the reference slide 21; and a sample slide 23 arranged to pass the split light from the beam splitter 22 and process the backscattered light from the sample 30. In some specific examples, the reference plate, spectroscope and sample plate are independently fused silica, etc., whose refractive index and thickness are less affected by temperature changes.

The interferometric module 20 is configured such that the distance between the focal plane 27 and the interferometric plane 28 of the interferometric objective lens module C varies during a measurement. During this measurement, the focal plane 27 and the interference plane 28 of the interference objective module C overlap at a position, which is usually a certain depth within the sample (i.e., the focal plane and the interference plane of the interference objective module C intersect during this measurement).

In this paper, FIGS. 3A-C show the relative positions of the focal plane (FP) 27 and the interference plane (IP) 28 of the Millau-type interference objective lens module during a measurement process. Before starting the measurement, the focal plane (FP) 27 is located at the interface of the sample sheet 23 and the sample 30 , and the interference plane (IP) 28 is located within the sample 30 without overlapping the focal plane (FP) 27 ( FIG. 3A ). When the objective lens is scanned towards the sample 30, the focal plane (FP) 27 and the interference plane (IP) 28 are spaced apart and then overlap at a certain depth within the sample 3 (Fig. 3B). Typically, the overlapping locations have the sharpest image quality during scanning measurements. As the scan continues deeper into the sample 3, the focal plane (FP) 27 and interference plane (IP) 28 will move away from each other (Fig. 3C). Therefore, the separation between the focal plane (FP) 27 and the interference plane (IP) 28 varies during the scanning of the sample.

Due to the asymmetry of the sample arm and the reference arm, the focal plane (FP) and the interference plane (IP) of the interference objective lens module do not overlap. In order to achieve this asymmetric property, in some embodiments, the Millau-type interference objective lens module includes at least two different media filled in the interference module 20 .

In order to obtain better interference imaging quality, in some specific examples, the Millau-type interference objective lens module shown in FIG. 2A is filled with at least two different media whose refractive index is similar to that of the sample to be tested. The first medium 241 and the second medium 242 fill the space inside the Mirau type interference objective lens module. In some specific examples, the first medium or the second medium is filled in the space between the objective lens 10 and the reference plate 21 . In some embodiments, the first medium is filled in the space between the reference plate 21 and the beam splitter 22 . The at least two different media have a similar refractive index to sample 3, ranging from about 1.2 to about 1.8. In some embodiments, the first medium has a refractive index in the range of about 1.3 to about 1.5. In some embodiments, the first medium includes water, silicone oil, silicone gel, ultrasonic gel, ethanol or glycerin, which has a refractive index ranging from about 1.3 to about 1.5, or a combination thereof. In some embodiments, the first medium includes water, silicone oil or glycerin. In some embodiments, the first medium includes silicone oil. In some specific examples, the second medium 242 different from the first medium is filled in the space between the beam splitter 22 and the sample slide 23 . In some embodiments, the second medium has a different refractive index than the first medium 241, but still has a refractive index in the range of about 1.2 to about 1.8. In some embodiments, the second medium includes silicone, such as ST-elastomer 10 or its corresponding elastomer.

In some embodiments, when the refractive index of sample 3 is greater than that of the skin, equations (1) to (3) will be satisfied:

n _{average sample} < n _{average reference} ......(1)

_dsample > _dreference ......(2)

d _樣品

n _平均參考

d _參考………(3)。 n _{average sample}

d _sample

n _{average reference}

dRefer _to ………(3).

，n代表穿過區域S中之各材料樣品臂的折射率，d代表各材料的厚度。「n _平均參考」表示區域R的平均折射率，意指參考臂的平均折射率，其被定義為

，n代表穿過區域S中之各材料參考臂的折射率，d代表各材料的厚度。「d _樣品」表示區域S的距離，「d _參考」表示區域R的平均折射率。 According to Fig. 2, "n _{average sample} " denotes the average refractive index of region S, meaning the average refractive index of the sample arm, which is defined as

, n represents the refractive index of each material sample arm passing through the region S, and d represents the thickness of each material. "n _{average reference} " means the average refractive index of region R, meaning the average refractive index of the reference arm, which is defined as

, n represents the refractive index of each material reference arm passing through the region S, and d represents the thickness of each material. "d _sample " represents the distance of the region S, and "d _reference " represents the average refractive index of the region R.

In some embodiments, when the refractive index of the sample 3 is less than that of the skin, equations (4), (5) and (3) will be satisfied.

n _{average sample} > n _{average reference} ......(4)

d _sample < d _reference ......(5)

d _樣品

n _平均參考

d _參考………(3)。 n _{average sample}

d _sample

n _{average reference}

dRefer _to ………(3).

The symbols in equations (4), (5) and (3) are defined the same as in equations (1), (2) and (3).

In some embodiments, in order to achieve asymmetry between the sample arm and the reference arm, the material and/or thickness of the sample sheet 23 is different from that of the beam splitter 22 .

In some embodiments, the thickness and/or material of the sample sheet 23 is changed/selected to satisfy equations (1) to (5). In some embodiments, the sample slice 23 is different in thickness and/or material from the beamsplitter 22 (and optionally from the reference slice 21 ). In some embodiments, the thickness and/or material of beam splitter 22 are changed/selected to satisfy equations (1) to (5). In some specific examples, the thickness and/or material of the beam splitter 22 are different from the sample sheet 23 (and optionally different from the reference sheet 21 ). In some embodiments, the material difference is characterized by a refractive index.

Figure 2B provides an exemplary interference image produced by the optical system designed according to Figure 2A, while the upper image is produced by a symmetrical design in which the same medium is used to fill the module 20, and the thickness of the beam splitter 22 and the reference plate 23 are the same . A better upper image is produced by an asymmetric design in which two different media are used to fill the interference objective lens module 20, and the thickness of the beam splitter 22 and the reference plate 23 are the same. All B-scan images are taken from human palms. B-scan images obtained with an asymmetrical design exhibit better sensitivity and resolution for the epidermis.

Figure 2C provides a graph of the SNR of an exemplary optical system comprising the Mirau-type interference objective lens module shown in Figure 2A. The upper curve is obtained from an asymmetric design in which two different media are used to fill the interference objective module and two beamsplitters 22 and reference plates 23 of different thicknesses are used. The lower curve is obtained from a symmetrical design that uses the same medium to fill the interference objective module 20, and the thickness of the beam splitter 22 and the reference plate 23 are the same. Signal-to-noise ratio (SNR) versus depth curves were estimated by averaging >15 B-scans of human skin. The overall SNR is improved by changing the traditional symmetric Miraux design to an asymmetric Miraux design with different dielectrics and different glass thicknesses.

With the exemplary Mirau-type interferometry disclosed in this case, the simultaneous movement of the focal plane (FP) and the interference plane (IP) can be achieved simply by moving the Mirau-type objective lens. Compared with Michelson-type and Linnik-type interferometry, Millau-type OCT is also more resistant to vibration, requires fewer optical components, and is lighter. One problem with Millau-type structures is the low degree of adjustability. Since the reference and sample arms share the same objective in Mirau-type interferometry, it is difficult to add an additional scan axis (e.g. a second axis) to compensate for the mismatch. Because the present invention can optionally use a second axis to compensate for mismatches, it is suitable for Millau-type OCT.

The interference objective lens module C is not limited to Mirau type, but can also be Michelson type, Linnik type or Mach Zehnder type. FIG. 4 provides an example of a Linnich-type interference objective lens module, which includes a beam splitter 41 for splitting source light into a reference objective lens 43 and a sample objective lens 42 . The reference objective 43 projects the split light to a reference mirror 44 to generate a reference arm, and the reference arm interferes with the sample arm backscattered from the sample 3 . During the measurement, the reference objective 43 and the sample objective 42 will be adjusted separately.

FIG. 5 provides an example of a Michelson-type interference objective lens interference module, which includes an objective lens 51 that transmits source light to a beam splitter 52 , and then the split light will be projected onto the sample 3 and a reference mirror 53 . Then, the reference arm and the sample arm from the reference mirror 53 interfere with the sample 3 to generate an interference signal. During the measurement, the objective lens 51 and the reference mirror 53 can be adjusted.

In order to adjust the overlapping position of the focal plane and the interference plane, in some specific examples, a refraction adjustment member 25 is arranged between the beam splitter 22 and the sample sheet 23 of the Millau type interference objective lens module, as shown in FIG. 6 . The first medium 241 and the second medium 242 are filled in the space inside the Millau type interference objective lens module. In some specific examples, the refraction adjusting member 25 includes a glass slide, a rotating plate, and the like. In some specific examples, the refraction adjusting member 25 is a rotating plate, which includes several parts with different thicknesses and/or refractive indices, as shown in FIG. 7 . The refraction adjustment member 25 (i.e., the rotating plate) can be divided into several parts, which include a thick glass slide 251 part and a thin glass slide 252 part (FIG. 7A), wherein the rotation axis 254 is located in the refraction adjustment member , the center of the rotating slide), and the optical axis 255 is located at the part of slides 251 and 252. In some specific examples, the refraction adjustment member 25 can be designed as shown in FIG. 7B , which has several glass inserts 253 with different thicknesses or refractive indices fused on the refraction adjustment member 25 . The optical properties of the various parts on the refraction adjusting member 25 can vary according to requirements.

The present invention provides another specific example of the Millau-type interference objective lens module, as shown in FIG. 8 . An exemplary Millau-type interference objective module includes a refraction-adjusting member 26 positioned between the beamsplitter 22 and the sample slide 23 . The first medium is filled in the space in the Millau-type interference objective lens module, as shown in FIG. 8 . In some embodiments, the refraction adjusting member 26 is a glass slide that can move along the longitudinal direction, and the longitudinal direction is the same as the scanning direction of the objective lens.

The present invention also provides a specific example of the Millau-type interference objective lens module as shown in FIG. 9 . In addition to the third medium 243 filling the space between the beam splitter 22 and the refraction adjustment member 26, and the fourth medium 244 filling the space between the refraction adjustment member 26 and the sample plate 23, the Millau type interference objective lens module has Same structure as in Figure 8. In some specific examples, the refractive index of the third medium 243 may be smaller than that of the fourth medium 244 . Since the third medium 243 and the fourth medium 244 have different refractive indices, the interference adjustment device 26 will move asymmetrically during the scanning of the objective lens, so that the average interference effect of the sample arm changes during the scanning observation process, so that the focus can be adjusted. The overlapping position of the plane and the interference plane.

FIG. 10 provides a graph of SNR for an exemplary optical system disclosed in this application. Figure 10A shows the results obtained for a system comprising the Mirau-type interference objective lens module shown in Figure 6, which has a glass slide as the refraction adjustment member 25; conversely, Figure 10B shows a system without the slide glass the result of. When the refraction adjustment member was inserted between the beamsplitter and the sample slide, the SNR signal at a depth of 0 to 150 μm ( FIG. 10A ) was significantly larger than that without the refraction adjustment member ( FIG. 10B ). However, as the refraction modulating member is removed, the SNR signal becomes larger at depths above 150 μm. This result can be observed in the interference images, as shown in Figures 11A-D. Figures 11A and 11B are interference images produced by the optical system corresponding to Figure 10A, while the images in Figures 11C and 11D are produced by the optical system corresponding to Figure 10B. When the optical system has a refraction adjustment member interposed between the beamsplitter and the sample plate, the image of the superficial skin layer is sharp (see arrows) (Fig. 11A and 11B), which represents the The focal plane and the interference plane overlap. Conversely, blurred signals (white stars) appeared in the deeper skin layers (Fig. 11C and 11D), which indicated that the focal and interference planes did not overlap. However, as the refraction accommodation member is removed, the image will be in focus in the deep skin (see arrow), but out of focus in the superficial skin (white star), as shown in Figures 11C and 11D . According to this result, the focal depth of observation, as well as the overlapping position of the focal plane and the interference plane, can be effectively changed through the optical system of the present invention.

12A-C provide interference images obtained by an optical system including the interference objective lens module shown in FIG. 9 . Before starting the scan measurement, the image signal was strong in the shallow sample (Fig. 12A). At the start of the scan, as the refraction modulating member approaches the sample sheet, the image of the deeper sample becomes sharper (Figures 12B and 12C).

In some specific examples, an interference objective lens module is provided, which includes an objective lens and an interference module, and the interference module includes a reference plate that is provided separately from the objective lens to provide a reference arm, and a A beam splitter for splitting the source light, and a sample plate for transmitting the split light from the beam splitter to provide a sample arm, wherein the interference module is constructed so that the focal plane of the interference objective lens module and The distance between the interference planes varies during a measurement, and wherein the focal plane of the interference objective lens module and the interference plane intersect during the measurement. In some embodiments, the interference objective lens module is immersed in at least two different media whose refractive index is close to that of the sample. In some embodiments, the interference objective lens module includes a first medium, which is filled in the space between the reference slide and the beam splitter; and a second medium, which is filled in the space between the beam splitter and the sample slide. In some embodiments, the at least two media have different refractive indices. In some embodiments, the different refractive indices range from about 1.2 to about 1.8. In some embodiments, the first medium includes water, silicone oil, or glycerin. In some embodiments, the second medium includes silica gel and the like. In some specific examples, the interference objective lens module is a Millau type interference objective lens module, a Michelson type interference objective lens module, a Linick type interference objective lens module, or a Mach-Zehnder type interference objective lens module.

In some embodiments, the sample slide has a different thickness and/or material than the beamsplitter. In some embodiments, the interference objective lens module is immersed in one or more media having a refractive index close to that of the sample. In some embodiments, the interference objective lens module includes a first medium, which is filled in the space between the reference slide and the beam splitter; and a second medium, which is filled in the space between the beam splitter and the sample slide. In some embodiments, the first medium and the second medium have different refractive indices. In some embodiments, the different refractive indices range from about 1.2 to about 1.8. In some embodiments, the first medium includes water, silicone oil, or glycerin. In some embodiments, the second medium includes silica gel and the like.

In some embodiments, the interference module further includes a refraction adjustment member positioned between the beam splitter and the sample slide. In some embodiments, the refraction adjustment member is a glass slide, a rotating plate, or the like. In some embodiments, the rotating plate includes several portions with different thicknesses and/or refractive indices. In some embodiments, the refraction modulating member is a longitudinally movable glass slide. In some specific examples, the interference module includes a third medium located between the beam splitter and the longitudinally movable glass slide, and a fourth medium located between the longitudinally movable glass slide and the sample slide, wherein the refraction of the third medium The index is smaller than the refractive index of the fourth medium.

In some embodiments, an apparatus/system is provided that includes: an illumination module configured to provide a source light to an optical interference module that converts the source light into a line of light and process light signals; an interference objective lens module disclosed in the case, which is used to process light from the optical interference module and process light signals generated by a sample; a two-dimensional camera, which is constructed to receive an interference signal backscattered by the sample; and a data processing module for processing the interference signal into an image.

In some embodiments, a method for imaging a sample is provided, which is performed by a device/system comprising the interference objective lens module of the present invention, wherein the interference module disclosed in the present case is configured to make the interference objective lens module The distance between the focal plane and the interference plane changes during a measurement period, and the focal plane and the interference plane of the interference objective lens module intersect during the measurement period.

The optical system and interference objective lens module of the present invention are used to adjust the observation depth of a sample with cell-level resolution. It is suitable for providing information on the surface or deep inside of samples such as skin or cornea. As far as the Millau type interference optical system is concerned, the high NA objective lens can minimize the aberration and optimize the resolution, and the interference objective lens module of the present invention can effectively improve its observation depth.

While preferred embodiments of the invention have been shown and described herein, it will be obvious to those skilled in the art that these embodiments are illustrative only. Numerous alterations, changes and substitutions can be made by those skilled in the art without departing from the invention. It should be understood that various alternatives to the embodiments of the invention described herein may be employed in practicing the invention. It is intended that the following claims define the scope of the invention and that methods and structures falling within the scope of these claims and their equivalents be covered thereby.

A: light source B: Optical interference module C: Interference objective lens module D: detector E: Data processing module R: area S: area 10: objective lens 20: Interference Module 21: Reference film 22: beam splitter 23: Sample sheet 241: The first medium 242: Second Medium 243: The third medium 244: The fourth medium 25: Refraction adjustment member 251: thick slide 252: thin slide 253: glass insert 254:Rotary axis 255: optical axis 26: Refraction adjustment member 27:Focal plane 28: Interference plane 3: Sample 30: sample 41: beam splitter 42: Sample objective lens 43: Reference objective lens 44: Reference Mirror 51: objective lens 52: beam splitter 53: Reference Mirror

A better understanding of the features and advantages of the present invention may be obtained by reference to the following detailed description and the following drawings, which illustrate illustrative embodiments employing the principles of the invention:

Figure 1 shows a schematic diagram of the optical system of this case.

FIG. 2A shows a specific example of the Millau-type interference objective lens module of the present invention.

Figure 2B provides exemplary interference images produced by the optical system designed according to Figure 2A, where the upper image is produced by a symmetric design and the lower image is produced by an asymmetric design.

Figure 2C provides a graph of the SNR produced by the optical system designed according to Figure 2A, where the upper curve results from a symmetric design and the lower curve results from an asymmetric design.

Figures 3A-C show the relative positions of the focal plane (FP) and the interference plane (IP) of the interference objective module during a sample scan.

FIG. 4 shows a specific example of an exemplary Linnicke-type interference objective lens module of the present invention.

FIG. 5 shows a specific example of an exemplary Michelson-type interference module of the present invention.

FIG. 6 shows a specific example of an exemplary Millau-type interference module provided with a refraction adjustment member.

7A/B show an example of the refraction adjustment member of FIG. 6 .

FIG. 8 shows a specific example of an exemplary Millau-type interference module provided with a refraction adjustment member.

FIG. 9 shows details of an embodiment of an exemplary Millau-type interference module provided with the refraction-adjusting member of FIG. 8. FIG.

Figures 10A/B show SNR plots for exemplary optical systems disclosed herein. FIG. 10A shows the results obtained by the system of the Millau-type interference objective lens module using a glass slide as the refraction adjustment member 25 shown in FIG. 6 . Figure 10B shows the results obtained for the system without slides.

11A-D show exemplary cross-sectional optical coherence tomography (OCT) images produced by optical systems corresponding to FIGS. 10A and 10B .

12A-C provide interference images generated by the optical system including an interference objective lens module as shown in FIG. 9 .

none

C: Interference objective lens module

R: area

S: area

10: objective lens

20: Interference Module

21: Reference film

22: beam splitter

23: Sample sheet

241: The first medium

242: Second Medium

27:Focal plane

28: Interference plane

3: Sample

Claims (22)

A kind of interference objective lens module, it comprises: an objective lens, and An interference module, the interference module includes: a reference plate arranged separately from the objective to provide a reference arm; a beam splitter for splitting the source light from the objective lens; and for transmitting the split light from the beam splitter to provide a sample slide of a sample arm, Wherein the interferometric module is configured such that the distance between the focal plane of the interferometric objective lens module and the interferometric plane varies during a measurement, and wherein the focal plane and the interferometric plane of the interferometric objective lens module intersect during the measurement. The interference objective lens module as claimed in claim 1, wherein the interference objective lens module is immersed in at least two different media, and the at least two different media have a refractive index close to that of the sample. The interference objective lens module as claimed in claim 2, wherein the interference objective lens module comprises a first medium, which is filled in a space between the reference plate and the beam splitter; and a second medium, which is filled in A space between the beamsplitter and the sample slide. The interference objective lens module as claimed in claim 3, wherein the at least two different media have different refractive indices. The interference objective lens module as claimed in claim 4, wherein the different refractive indices are in the range of about 1.2 to about 1.8. The interference objective lens module as claimed in claim 3, wherein the first medium contains water, silicone oil or glycerin. The interference objective lens module as claimed in claim 3, wherein the second medium includes silica gel. The interference objective lens module as claimed in claim 1, wherein the sample sheet has a thickness and/or material different from that of the beam splitter. The interference objective lens module as claimed in claim 8, wherein the interference objective lens module is immersed in one or more media with a refractive index close to the sample. The interference objective lens module as claimed in claim 8, wherein the interference objective lens module comprises a first medium, which is filled in a space between the reference plate and the beam splitter; and a second medium, which is filled in A space between the beamsplitter and the sample slide. The interference objective lens module as claimed in claim 10, wherein the first medium and the second medium have different refractive indices. The interference objective lens module as claimed in claim 10, wherein the different refractive indices are in the range of about 1.2 to about 1.8. The interference objective lens module as claimed in claim 10, wherein the first medium contains water, silicone oil or glycerin. The interference objective lens module as claimed in claim 10, wherein the second medium comprises silica gel. The interference objective lens module as claimed in claim 1, wherein the interference objective lens module comprises a refraction adjusting member located between the beam splitter and the sample plate. The interference objective lens module as claimed in claim 15, wherein the refraction adjusting member is a glass plate or a rotating plate. The interference objective lens module as claimed in claim 16, wherein the rotating plate includes several parts with different thicknesses and/or refractive indices. In the interference objective lens module as claimed in claim 16, wherein the refraction adjusting member is a longitudinally movable glass slide. The interference objective lens module as claimed in claim 18, wherein the interference objective lens comprises a third medium located between the beam splitter and the longitudinally movable glass slide, and a third medium located between the longitudinally movable glass slide and the sample slide A fourth medium in between, wherein the refractive index of the third medium is smaller than the refractive index of the fourth medium. The interference objective lens module as described in claim 1, wherein the interference objective lens module is Mirau type (Mirau type) interference objective lens module, Michelson type (Michelson type) interference objective lens module, Linnik type (Linnik type) Interference objective lens module, or Mach Zehnder type (Mach Zehnder type) interference objective lens module. A device/system comprising: an illumination module configured to provide a source light to an optical interference module that converts the source light into a line of light and processes the light signal; An interference objective lens module as described in Claim 1, which is used for processing light from the optical interference module and processing an optical signal generated by a sample; a two-dimensional camera configured to receive an interference signal backscattered by the sample; and A data processing module is used for processing the interference signal into an image. A method for imaging a sample, which is carried out by a device/system as claimed in claim 21, wherein the interference module is constructed so that the distance between the focal plane and the interference plane of the interference objective lens module is at a changes during the measurement, and intersects the focal plane and the interference plane of the interference objective lens module during the measurement.

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