WO2021000568A1 - 一种数字化病理成像设备 - Google Patents

一种数字化病理成像设备 Download PDF

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Publication number
WO2021000568A1
WO2021000568A1 PCT/CN2020/071390 CN2020071390W WO2021000568A1 WO 2021000568 A1 WO2021000568 A1 WO 2021000568A1 CN 2020071390 W CN2020071390 W CN 2020071390W WO 2021000568 A1 WO2021000568 A1 WO 2021000568A1
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Prior art keywords
lens
digital
light
imaging device
hole section
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PCT/CN2020/071390
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English (en)
French (fr)
Inventor
唐玉豪
何俊峰
吴庆军
于綦悦
韦建飞
邓建
刘亚鸿
周雄兵
王阳
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达科为（深圳）医疗设备有限公司
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Publication of WO2021000568A1 publication Critical patent/WO2021000568A1/zh

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    • G—PHYSICS
    • G02—OPTICS
    • G02B—OPTICAL ELEMENTS, SYSTEMS OR APPARATUS
    • G02B21/00—Microscopes
    • G02B21/06—Means for illuminating specimens
    • G—PHYSICS
    • G02—OPTICS
    • G02B—OPTICAL ELEMENTS, SYSTEMS OR APPARATUS
    • G02B21/00—Microscopes
    • G02B21/36—Microscopes arranged for photographic purposes or projection purposes or digital imaging or video purposes including associated control and data processing arrangements
    • G02B21/361—Optical details, e.g. image relay to the camera or image sensor
    • G—PHYSICS
    • G02—OPTICS
    • G02B—OPTICAL ELEMENTS, SYSTEMS OR APPARATUS
    • G02B21/00—Microscopes
    • G02B21/36—Microscopes arranged for photographic purposes or projection purposes or digital imaging or video purposes including associated control and data processing arrangements
    • G02B21/365—Control or image processing arrangements for digital or video microscopes

Definitions

  • the present invention relates to the field of optical imaging technology, in particular to a digital pathological imaging device.
  • Digital pathology refers to the application of computers and networks to the field of pathology. It is a technology that combines modern digital systems with traditional optical amplification devices. It mainly uses digital pathology imaging equipment to scan sliced tissues.
  • the existing digital pathology imaging equipment generally includes a microscope objective lens and a light source system.
  • the light irradiated by the light source usually has a Gaussian distribution, with the highest brightness in the central area of the microscopic field and low brightness around it.
  • This problem of uneven illumination is manifested in digital microscopes as digital images showing uneven brightness, especially in digital pathology.
  • digital images of multiple microscopic fields need to be spliced, and uneven illumination will lead to light and dark fluctuations in the spliced digital pathological images, which must be compensated by digital image brightness adjustment algorithms, otherwise it will cause visual fatigue to the diagnostician.
  • Reduce diagnosis efficiency and diagnosis accuracy Generally, the size of digital pathological images is relatively large. For such large data, brightness compensation is low in calculation efficiency, and the overall time-consuming of digital pathological imaging is relatively high.
  • the existing micro objective lens is generally composed of an entrance pupil lens, an aperture stop, an intermediate lens or a combination of an intermediate lens, and an exit pupil lens.
  • the function is to enlarge the local area of the observation object to realize the observation of the microscopic world. .
  • the light from the observed object first passes through the entrance pupil lens and irradiates into the lens barrel, and then is enlarged under the action of the aperture stop and the intermediate lens, and finally shines out of the lens barrel through the exit pupil lens to achieve a clear Imaging.
  • the performance of the microscope objective mainly consists of: numerical aperture, field of view, magnification, and effective focal length.
  • the numerical aperture describes the size of the light-receiving cone angle of the objective lens, which directly determines the light-receiving ability and optical resolution of the microscope objective. For example: the larger the numerical aperture, the stronger the light-receiving ability of the microscope objective, and the higher the optical resolution; It is the range of observation objects that can be magnified and imaged by the microscope objective.
  • the magnification is the ratio of the field of view to the imaging area. Generally, when the imaging area is fixed, the larger the magnification, the smaller the field of view, and the greater the number of intermediate lenses required.
  • the effective focal length is the distance from the principal point of the optical system to the focal point on the optical axis.
  • ideal microscope objectives For users of optical microscopes, ideal microscope objectives have the following characteristics: a larger field of view and a larger numerical aperture, so that all the details of the ultrastructure of the observed object can be observed at one time, and the efficiency of microscopic observation is improved. Reduce the burden of observation.
  • the various parameters that determine the performance of the microscopic objective it can be seen that for the clear imaging of the ultrastructure, it is necessary to increase the numerical aperture and magnification, which will inevitably lead to the reduction of the field of view, the increase of the number of intermediate lenses, and the The volume and production cost of the objective lens and the difficulty of assembly have increased sharply.
  • the magnification of the microscope objective lens can realize the precise observation of pathological slices from the macroscopic to the ultra-microstructure, and ensure the accuracy of pathological diagnosis; due to the limitation of the field of view, the doctor must operate the translation stage when performing the microscopic observation to achieve the correct
  • the observation and diagnosis of each local tissue in the entire slice prevents misdiagnosis and missed diagnosis; the above shows that the limitations of traditional microscope performance have caused the complexity of using optical microscopes, and it usually takes more than 20 minutes for doctors to observe a pathological slice, which is extremely inefficient
  • the labor burden and intensity of pathologists are huge, which not only threatens the physical and mental health of pathologists, but also increases the risk of missed diagnosis and misdiagnosis of pathological diagnosis.
  • the optical microscope due to the large volume of the microscope objective lens, the optical microscope has a large volume, which is not conducive to the large number of placements in pathology departments with limited area. At the same time, the high price is not conducive to the procurement of hospitals and also leads to the cost of pathological diagnosis and medical treatment. increase.
  • the present invention provides a digital pathological imaging device, the main purpose of which is to make the light emitted by the light source more uniform, and the numerical aperture and field of view of the microscope objective lens are large enough, while the volume is smaller and the cost is lower.
  • the present invention mainly provides the following technical solutions:
  • the embodiment of the present invention provides a digital pathological imaging device, including a microscopic lighting device, a microscopic objective lens, and a digital image sensor;
  • the microscopic lighting device includes a light source, a Mie scattering device, an optical cavity, and a condenser; the light source is located on one side of the Mie scattering device, the condenser is located on the other side of the Mie scattering device, and the Mie scattering device is sleeved on the optical In the cavity; the light source is used to emit light to illuminate the Mie scattering device; the Mie scattering device is used to diverge and illuminate the light from the light source to the condenser; the condenser is used to focus the light from the Mie scattering device and output it to the second On a lens
  • the microscopic objective lens includes a first lens and a second lens arranged in sequence along the optical axis direction, the microscopic objective lens receives the light incident from the object under test through the first lens; the surface of the first lens facing the object surface is the front The surface, the surface facing the image surface is the back surface; the surface of the second lens facing the object surface is the front surface, and the surface facing the image surface is the back surface; the front surface of the first lens is coated with a first transflective optical medium spectroscopic film, The rear surface of the second lens is plated with a second semi-transmissive and semi-reflective optical medium splitting film;
  • the digital image sensor is used to receive the light incident from the second lens and perform digital imaging.
  • the present invention is further configured as: the number of the micro-illumination devices is multiple, and they are arranged in sequence to form an array of the micro-illumination devices;
  • the number of the microscopic objective lens is equal to the number of the microscopic illuminating device and corresponds one to one to form an objective lens array;
  • the number of the digital image sensors and the number of the microscope objective lenses are equal and correspond one to one to form a sensor array.
  • the present invention is further provided that: when the sensor array is used to move in the first direction, the images formed by the digital image sensors are arranged in the second direction in sequence without intervals; the first direction is perpendicular to the second direction.
  • the present invention is further configured as follows: the sensor array has N parallel and spaced rows along the first direction, and N is an integer greater than or equal to 2;
  • the offset of the N1th row is the distance of FoV; when N2 is equal to N, the N2th row protrudes from the N1th row along the second direction by the distance of FoV; FoV is the image formed by the digital image sensor in the second direction Size.
  • the present invention is further configured as: the number of digital image sensors in each row is more than two, and they are arranged sequentially along the second direction;
  • the distance between two adjacent digital image sensors in each row in the second direction is equal, and both are r1.
  • N is the smallest integer greater than or equal to (W+r)/FoV;
  • W is the size of the digital sensor along the second direction; r is the smallest distance that can be achieved in the second direction by the processing technology of two adjacent digital image sensors in the same row.
  • the present invention is further configured as follows: the interval between two adjacent rows in the first direction is r2, and r2 is the minimum interval that can be achieved in the first direction by the processing technology of the digital image sensor in the two adjacent rows.
  • the present invention is further configured as: the digital pathological imaging equipment further includes a fixing plate, and the fixing plate is provided with mounting holes;
  • the number of the mounting holes is equal to the number of the microscopic objective lens and corresponds to each other; each of the microscopic objective lenses is mounted in the corresponding mounting hole one to one, and the first lens is located at one end of the mounting hole, and the second lens Located at the other end of the mounting hole.
  • the outer diameter of the first lens is smaller than the outer diameter of the second lens
  • the mounting hole includes a first hole section, a second hole section, and a third hole section that are sequentially connected, and the outer diameters of the first hole section, the second hole section, and the third hole section are sequentially reduced;
  • the first lens is fixed on the first hole section
  • the second lens is fixed on the third hole section
  • the present invention is further provided as follows: a first notch is provided on the side wall of the first hole section, the first notch is filled with a light adhesive, and the first lens is fixed to the all through the light adhesive. On the first hole section;
  • a second notch is provided on the side wall of the third hole section, and the second notch is filled with a light adhesive, and the second lens is fixed on the first lens through the light adhesive.
  • the present invention is further provided as follows: when the side wall of the first hole section is provided with a first notch and the side wall of the third hole section is provided with a second notch, the first notch is located near the first hole section. At one end of the two hole sections, the second gap is located at an end of the third hole section away from the second hole section.
  • the second hole section is in the shape of a frustum, and the center line of the second hole section coincides with the center line of the first lens or the second lens.
  • the light source is a light emitting diode or a semiconductor laser.
  • the Mie scattering device is a solid optical device with Mie scattering medium particles distributed, the optical device is transparent or semi-transparent, and the refractive index of the optical device is smaller than that of the Mie scattering medium particles. Refractive index.
  • the optical cavity is a hollow cylindrical closed cavity with openings at both ends wrapped outside the Mie scattering device, and its inner wall is a mirror surface that reflects light, or a black oxide layer surface.
  • the condenser lens is an optical lens or a combination of optical lenses that can shrink the uniform light propagation direction to perform condensed light irradiation.
  • the present invention is further provided that: the light source is fixed on one side of the Mie scattering device by optical glue, and the condenser is fixed on the other side of the Mie scattering device by optical glue.
  • the first lens and the second lens are circular lenses, and there is a gap between the first lens and the second lens; the gap is filled with air or liquid, or other lenses and other lens combinations are arranged in the gap.
  • the front surface and the back surface of the first lens are aspherical, and the front and back surfaces of the second lens are aspherical.
  • the digital pathological imaging device further includes an image data acquisition controller, a data bus interface, a random access memory, a central processing unit, a non-volatile memory and a display output port;
  • the digital image sensor is connected to the image data acquisition controller through a parallel data interface, the image data acquisition controller is used to read the digital image data transmitted by the digital image sensor; the image data acquisition controller and the random access memory are connected through the data bus interface, The image data acquisition controller transmits digital image data to the random access memory through the data bus interface; the central processing unit is connected to the random access memory, the non-volatile memory and the display output port through the circuit bus, and the central processing unit is used to read the digital image in the random access memory Data, the digital image data is stored in the non-volatile memory, and at the same time output to the display output port for image data display.
  • the present invention is further configured as: the image data acquisition controller and the central processing unit are processor chips or electronic systems with serial calculation and logic processing, or processor chips or electronic systems with parallel calculation and logic processing, or both Processor chip or electronic system for serial and parallel computing and logic processing.
  • the present invention is further configured as: the data bus interface is a data bus and hardware interface from the image data acquisition controller to the random access memory.
  • the random access memory is a register with data buffer access; and/or, the non-volatile memory is a computer memory that does not disappear after the power is turned off.
  • the present invention is further configured as a method or communication protocol for the image data acquisition controller to receive the digital image sensor in parallel or serially to acquire and process the image data, and use the serial or parallel data processing algorithm to pre-process the image data.
  • the present invention is further configured as: the random access memory is used to write the read bus interface data in a direct memory access manner.
  • the present invention is further configured as: the central processing unit is used to read the data stored in the random access memory, and write the data read in the random access memory into the display output port in a direct memory access manner.
  • the present invention is further configured as follows: the non-volatile memory is used to read data stored in the random access memory, and write the read random access memory data in a direct memory access manner.
  • the digital pathological imaging equipment of the present invention has at least the following beneficial effects:
  • the white light output by the microscopic lighting device has uniform illumination and uniform spectral distribution.
  • the traditional microscopic light source has a Gaussian distribution, and the spectral distribution of different lighting is not necessarily the same; the microscopic lighting device can ensure a high light source utilization rate ,
  • the traditional light source has a large volume and cannot guarantee the utilization rate of the light source;
  • the structure of the micro-illumination device is simple and simple to assemble, and it only needs one optical lens to achieve focused illumination.
  • the traditional light source requires a combination of multiple lenses to achieve a relatively uniform light source;
  • the light source adopts light-emitting diodes, which has low power consumption and low price, and can be used continuously for more than 50,000 hours. Therefore, compared with traditional light sources, the present invention is stable, reliable and has a long use time.
  • the microscopic objective lens of the present invention adopts a catadioptric structure, which not only can realize a high-performance optical microscopic objective lens with a very small number of lenses, but also increases the path length of light propagating in the optical system, so that the microscopic objective lens can reach The optical performance of the two lenses is maximized by the diffraction limit.
  • the microscopic objective of the present invention reduces the number of lenses while ensuring high performance, which greatly reduces the volume of the objective lens and reduces the production cost.
  • the microscopic objective lens of the present invention can realize the convergence of imaging light, form a high-energy imaging focus, greatly improve the signal-to-noise ratio of imaging, and achieve a large microscopic field of view High-quality and clear imaging;
  • the microscope objective of the present invention fully meets the miniaturization requirements of optical microscopes, in particular, fully meets the needs of high-speed digital pathology scanning, can increase the traditional digital pathology scanning time by more than 10 times, and fully meets the digital pathology technology High-efficiency and precise application requirements in clinical pathological diagnosis.
  • the first lens array and the second lens array form a new objective lens array, which can simultaneously perform microscopic imaging of multiple tissue regions in close proximity, effectively realizing efficient pathological tissue chip observation and diagnosis, and high-speed digital pathological scanning.
  • a plurality of microscopic lighting devices are arranged in sequence to form a microscopic lighting device array, which can meet the lighting requirements of the microscopic objective lens array, and the illumination is more uniform.
  • the multiple mounting holes are arranged in the same array as the microscope objective lens, and each microscope objective lens can be installed in the corresponding mounting hole in a one-to-one correspondence.
  • the microscope objectives arranged in an array are fixed.
  • the central processing unit first receives the image data transmitted from the USB and other external device interfaces, and then writes the data into the random access memory, then reads the data in the random access memory and sends it to the display output port. After the display is over, the data stays in the display cache, and the central processing unit transmits the data in the random access memory to the non-volatile memory through the bus. This process is controlled by the central processing unit, which usually results in slow data transmission, which usually takes more than 10 seconds or even several minutes. For example, when an interrupt processing task occurs, the central processing unit needs to suspend the current data transmission task, and after the interrupt processing task ends , The central processing unit needs to reply to the data transmission task, and too many interrupt processing tasks can cause the data transmission speed to decrease.
  • the data transmission process does not have the intervention of the central processing unit.
  • the control program controls the central processing unit to switch the control of the data bus to the bus controller, thereby realizing the direct transmission of data from the bus to the random access memory.
  • the data transmission It belongs to end-to-end transmission, there is no interruption, and the bus transmission speed is large, which can realize higher-speed data transmission.
  • the data transmission for display and the data transmission for non-volatile memory belong to concurrent data transmission, which are carried out at the same time, and belong to direct memory reading and data transmission. Therefore, the upper limit of the data speed is Limited to the display port and non-volatile memory speed, give full play to the advantages of data bus transmission, so that the data transmission speed reaches the limit.
  • FIG. 1 is a schematic structural diagram of a digital pathological imaging device according to an embodiment of the present invention
  • FIG. 2 is a schematic diagram of the structure of a micro-illumination device provided by the present invention.
  • Fig. 3 is a schematic diagram of the light path of the micro-illumination device in Fig. 2;
  • Fig. 4 is a schematic diagram of the application of the microscopic lighting device of the present invention in digital pathological microscopic imaging
  • Fig. 5 is a microscopic image when the micro-illumination device of the present invention is used for illumination
  • Figure 6 is a microscopic image when illuminated by a traditional microscopic lighting device
  • Fig. 7 is a structure and optical path diagram of the microscope objective lens of the present invention.
  • Fig. 8 is a structural diagram of the first lens of the microscope objective lens of the present invention.
  • FIG. 9 is a structural diagram of the second lens of the microscope objective lens of the present invention.
  • FIG. 11 is a light fan diagram of the longitudinal section of the optical system of the microscope objective lens of the present invention.
  • FIG. 12 is a light fan diagram of the light characteristics of the cross section of the microscope objective optical system of the present invention.
  • Figure 13 is a longitudinal section of the optical path fan diagram of the microscope objective optical system of the present invention.
  • Figure 14 is a cross-section of the optical path fan diagram of the microscope objective optical system of the present invention.
  • Fig. 15 is a point diagram of the optical system of the microscope objective lens of the present invention.
  • Fig. 16 is a field curvature diagram of the optical system of the microscope objective lens of the present invention.
  • Figure 17 is a distortion diagram of the optical system of the microscope objective lens of the present invention.
  • FIG. 18 is a schematic diagram of the structure of a microscopic lighting device array provided by the present invention.
  • Fig. 19 is a cross-sectional view of the microscope objective lens array of the present invention.
  • Fig. 20 is a schematic diagram of imaging of the micro objective lens array of the present invention.
  • FIG. 21 is an array arrangement of a combination of a microscope objective lens and a digital image sensor according to an embodiment of the present invention.
  • Fig. 22 is an array arrangement of a combination of a microscope objective lens and a digital image sensor according to another embodiment of the present invention.
  • FIG. 23 is an array arrangement of digital image sensors according to an embodiment of the present invention.
  • FIG. 24 is an array arrangement of digital image sensors according to another embodiment of the present invention.
  • 25 is a schematic structural diagram of a fixing plate provided by an embodiment of the present invention.
  • 26 is a schematic cross-sectional structure diagram of a microscope objective lens mounted on a fixed plate provided by an embodiment of the present invention.
  • FIG. 27 is a hardware implementation structure and data processing flowchart of the digital image big data high-speed transmission of the digital pathological imaging device of the present invention.
  • Fig. 28 is a hardware realization structure diagram of the digital image big data high-speed transmission of the digital pathological imaging device of the present invention.
  • a digital pathological imaging device proposed by an embodiment of the present invention includes a microscope objective lens 1, a digital image sensor 2 and a microscope illumination device 3.
  • the microscopic lighting device 3 includes a light source 101, a Mie scattering device 103, an optical cavity 102 and a condenser lens 105; the light source 101 is located on one side of the Mie scattering device 103, and the condenser lens 105 is located on the other side of the Mie scattering device 103.
  • the Mie scattering device 103 is set in the optical cavity 102; the light source 101 is used to emit light to illuminate the Mie scattering device 103; the Mie scattering device 103 is used to diverge and illuminate the light from the light source 101 to the condenser 105 Top; Condenser 105 is used to focus the light incident by the Mie scattering device 103 and output it to the measured object, such as the observed cell 301.
  • the microscope objective lens 1 includes a first lens 502 and a second lens 505 that are sequentially arranged along the optical axis direction. The microscope objective lens 1 receives the light incident from the subject through the first lens 502.
  • the surface of the first lens 502 facing the object surface 50 is the front surface, and the surface facing the image surface 507 is the back surface;
  • the surface of the second lens 505 facing the object surface 50 is the front surface, and the surface facing the image surface 507 is the back surface;
  • the front surface of the lens 502 is coated with a first semi-transmissive and semi-reflective optical medium spectroscopic film 501, and the rear surface of the second lens 505 is coated with a second semi-transparent and semi-reflective optical medium spectroscopic film 506.
  • the digital image sensor 2 is used to receive the light incident from the second lens 505, and the digital image sensor 2 can process the received light and convert it into electrical signal output for digital imaging.
  • the technical principle of the micro-illumination device 3 is as follows: as shown in Figures 2 and 3, the core device of the micro-illumination device 3 is a solid optical device filled with Mie scattering medium particles 104, which is transparent or semi-transparent. Transparent solid, made of optical resin or optical glass, has the performance of uniformly scattering and outputting the incident light beam.
  • a light source 101 and a condenser 105 are respectively placed on both sides of the Mie scattering device 103.
  • the light source 101 can be fixed on one side of the Mie scattering device 103 by optical glue
  • the condenser 105 can be fixed on the other side of the Mie scattering device 103 by optical glue.
  • One end of the light source 101 is a beam incident end, and one end of the condenser lens 105 is a beam output end.
  • a hollow lens tube 306 is wrapped outside the Mie scattering device 103 (as shown in FIG. 4).
  • the mirror The inner wall of the barrel 306 is coated with a total reflection film. In order to further reduce the cost and the illumination brightness is sufficient, the inner wall of the lens barrel 306 may be subjected to black oxidation treatment.
  • the Mie scattering device 103 When the light beam emitted by the light source 101 irradiates the Mie scattering device 103, because the device is filled with medium particles, a large amount of Mie scattering will occur when the light beam encounters these particles. The scattered light will continue to pass through the Mie scattering device 103. Scattering and superimposing are performed on the ground, and finally output light with uniform illumination.
  • the light scattered in the Mie scattering device 103 is reflected by the inner wall of the lens barrel 306, and the scattering, superposition and reflection occur continuously during the period, resulting in less light intensity loss.
  • the light intensity output by the Mie scattering device 103 is relatively bright.
  • the scattered light during the Mie scattering period illuminates the inner wall of the lens barrel 306 and will not reflect or reflect very weak light, resulting in loss of light transmission in the Mie scattering device 103 Larger, weaker light output during Mie scattering.
  • the light source 101 adopts color light-emitting diodes
  • the red, blue, and green light-emitting diodes cannot be integrated in the same position.
  • the condenser 105 After the condenser 105, three focal points located at different positions are formed, resulting in microscopic observation Color deviation occurs.
  • the degree of Mie scattering has nothing to do with the wavelength, and the nature of the photon remains regardless of the scattering. Therefore, through the Mie scattering device 103, although the three kinds of light-emitting diodes are in different positions, a stable uniform white color is still obtained Output, and can pass through the condenser 105 to form a focal point.
  • the white light emitted by each diode has different spectral components.
  • the white light output by the Mie scattering device 103 although the light emitting diodes are different,
  • a stable and uniform white light output can still be formed, which improves the stability of the light source 101.
  • FIG. 3 is a schematic diagram of the optical path of the uniform light microscopic illumination device 3 based on Mie scattering of the present invention.
  • the arrow 201 is the light emitted by the light source 101
  • the arrow 202 is the light scattered by the Mie scattering medium particles 104
  • the arrow 203 is the scattered light irradiated on the wall of the optical cavity 102 for reflection
  • the arrow 204 is the light that passes through the Mie scattering device.
  • the arrow 205 is the light condensed by the condenser 105
  • 206 is the illuminating surface formed by the condensing light.
  • the above-mentioned light source 101 may be a light emitting diode or a semiconductor laser.
  • the Mie scattering device 103 may be a solid optical device in which Mie scattering medium particles 104 are distributed.
  • the Mie scattering medium particles 104 are distributed inside the solid optical device.
  • the optical device is transparent or semi-transparent.
  • the refractive index of the optical device is smaller than the refractive index of the Mie scattering medium particles 104.
  • the optical cavity 102 may be a hollow cylindrical closed cavity with openings at both ends wrapped outside the Mie scattering device 103, and its inner wall is a mirror surface that reflects light, or a black oxide layer surface.
  • the condenser lens 105 is an optical lens or a combination of optical lenses that can shrink the uniform light propagation direction for condensed light irradiation.
  • the above-mentioned light source 101 may be a micro LED light-emitting chip 301
  • the Mie scattering device 103 is a Mie scattering microrod 303
  • the optical cavity 102 is a lens barrel 306
  • the condenser 105 is Plano-convex lens 307.
  • the uniform light micro-illumination device 3 based on Mie scattering includes a micro LED light-emitting chip 301, a Mie scattering micro-rod 303, a lens barrel 306, and a plano-convex lens 307.
  • the Mie scattering micro-rod 303 is based on transparent polycarbonate 305, in which lactic acid-glycolic acid polymer (PLGA) or polyvinyl alcohol (PVA) is doped as the material, and the diameter is 1-100 nanometers.
  • the sphere 304 is a small cylindrical optical device, and the nano-microsphere 304 is the aforementioned Mie scattering medium particle 104.
  • the diameter of the cylinder is the same as or similar to the diameter of the LED light-emitting part.
  • the refractive index of polycarbonate is smaller than that of the nano-microspheres 304.
  • the distribution of the nano-microspheres 304 is random, so that incident light can be irradiated to the nano-microspheres 304. , And Mie scattering occurs.
  • the lens barrel 306 is an opaque hollow cylinder covering the surface of the Mie scattering micro-rod 303, and its inner wall has a light reflecting mirror coating, which can reflect Mie scattered light to ensure that the emitted light has a strong brightness.
  • the plano-convex lens 307 is a lens with two surfaces, one surface is a flat surface and the other surface is a spherical surface, which converges the emitted light of the Mie scattering micro-rod 303, and the distance of the convergence point is equal to the focal distance of the plano-convex lens 307 .
  • the micro LED light-emitting chip 301 and the plano-convex lens 307 are respectively bonded to the input end and output end of the Mie scattering micro-rod 303 using UV curing optical adhesive 302, and the light-emitting surface of the micro LED light-emitting chip 301 and the Mie scattering micro-rod
  • the input end surface of 303 is glued, and the plane surface of the plano-convex lens 307 is glued to the output end of the Mie scattering microrod 303.
  • An embodiment of the uniform light micro-illumination device 3 based on Mie scattering the method of use is as follows: As shown in FIG. 4, the micro LED light-emitting chip 301 is first energized, the surface of the LED emits light, and the light beam is Mie scattering occurs inside the Mie scattering micro-rod 303, so that uniform white light is output from the Mie scattering micro-rod 303 and irradiated on the plane surface of the plano-convex lens 307. Through the refraction of the plano-convex lens 307, the uniform white light is emitted from the flat lens. The light 308 is converged and irradiated on the focal point of the plano-convex lens 307.
  • the tissue section is located between the slide glass 309 and the cover glass 311.
  • the position of the tissue section is at the focal point of the uniform white light.
  • the uniform white light is transmitted through the tissue section to form object light, which is irradiated into the microscope objective lens 1 of the optical microscope.
  • the object light is magnified and imaged on the digital image sensor 2.
  • the computer reads and encodes the data of the digital image sensor 2 to form a digital microscopic image, which is displayed on the display. Because the light irradiated on the tissue cells is uniformly irradiated white light, the digital microscopic image will not be able to observe the background of the original LED light with Gaussian distribution of light and dark, but an image with uniform background light.
  • FIG. 5 is a microscopic image when illuminated by a uniform light microscopic illuminator 3 based on Mie scattering of the present invention
  • FIG. 6 is a microscopic image when illuminated by a traditional microscopic illuminator.
  • 402 in FIG. 6 indicates that the center of the image is bright when using traditional lighting
  • 403 indicates that the surroundings of the image are dark when using traditional lighting.
  • the above-mentioned microscopic objective lens 1 is a catadioptric objective lens.
  • the first lens 502 and the second lens 505 are sequentially included from the surface of the object to be observed (object surface 50) to the imaging surface (image surface 507).
  • the first lens 502 is a meniscus lens
  • the front surface facing the object surface 50 is a concave surface
  • the rear surface facing the image surface 507 is a convex surface.
  • the second lens 505 is a meniscus lens
  • the front surface facing the object surface 50 is a concave surface
  • the rear surface facing the image surface 507 is a convex surface.
  • the curvatures of the front and rear surfaces of the first lens 502 and the second lens 505 are different.
  • the aperture stop is located at the rear surface of the first lens 502.
  • the front surface of the first lens 502 and the rear surface of the second lens 505 are both coated with a semi-transmissive and semi-reflective optical medium spectroscopic film.
  • the semi-transmissive and semi-reflective optical medium spectroscopic film is an optical coating that can transmit incident light along the incident direction and continue to propagate, and at the same time make the incident light reflect in the incident reverse direction and continue to propagate in the opposite direction of incident, and pass through the incident direction.
  • the light that passes and continues to propagate is transmitted light, and the light that is emitted in the reverse direction of incidence and continues to propagate in the reverse direction of incidence is reflected light.
  • the sum of the energy of reflected light and transmitted light is equal to the energy of incident light. Reflected in that the sum of the intensity of the reflected light and the transmitted light is equal to the intensity of the incident light.
  • the specific performance parameters of the aforementioned microscope objective lens 1 may be: the field of view diameter is 1 mm, the numerical aperture is 0.6, the effective focal length is 0.78 mm, the entrance pupil diameter is 1.17 mm, and the field of view range is 1.17 mm , The total length of the system is 4.23 mm, the magnification is 5.14 times, the imaging resolution is 0.24 ⁇ m/pixel, the working wavelength is visible light wavelength region from 0.4 ⁇ m to 0.7 ⁇ m, and the design wavelength is 0.643 ⁇ m, 0.591 ⁇ m, 0.542 ⁇ m, 0.5 ⁇ m, 0.466 microns, of which the design center wavelength is 0.542 microns.
  • the above parameters meet the needs of optical microscope imaging and equipment miniaturization, and meet the needs of digital pathology scanning efficiency improvement and high-quality microscopic imaging.
  • the main performance parameters of the aforementioned microscope objective lens 1 can specifically satisfy the following relationships:
  • NA represents the numerical aperture
  • n represents the refractive index of the working medium
  • ⁇ represents the half angle of the maximum cone angle of the incident light.
  • ⁇ represents the half-angle of the maximum cone angle of the incident light
  • EPD represents the entrance pupil diameter
  • EFL represents the effective focal length
  • ⁇ represents the imaging resolution
  • ⁇ represents the pixel size of the image sensor
  • Mag represents the magnification
  • U represents the unit length; in this example, ⁇ is specifically 1.12 microns, U is specifically 1 micron, and Mag is specifically 5.14. Therefore, the imaging resolution The rate is specifically 0.24 microns/pixel.
  • the materials of all the lenses of the aforementioned microscopic objective lens 1 can be glass with a low melting point and high and low dispersion.
  • the above-mentioned material high and low dispersion matching that is, the first lens 502 is made of high dispersion material glass and the second lens 505 is made of low dispersion material glass, or the first lens 502 is made of low dispersion material glass and the second lens 505 is made of high dispersion material glass.
  • An embodiment of the microscopic objective lens 1, as shown in FIG. 7, is specifically an object surface 50, a first lens 502, a second lens 505, and an image surface 507 respectively arranged from left to right along the optical axis direction.
  • the object plane 50 is located at the far left and finite distance
  • the image plane 507 is located at the far right finite distance.
  • the front surface of the first lens 502 and the rear surface of the second lens 505 are coated with a semi-transparent and semi-reflective optical medium spectroscopic film. .
  • the semi-transmissive and semi-reflective optical medium spectroscopic film is specifically: a semi-transparent and semi-reflective optical medium spectroscopic coating, which utilizes its optical performance to realize part of the light incident on the coating surface is transmitted and some is reflected.
  • An embodiment of the microscopic objective lens 1 of the present invention as shown in Fig. 7, the propagation path of light in the system is as follows: first along the optical axis, the light from the observed object is irradiated to the first semi-transparent plate
  • the front surface of the first lens 502 of the reflective optical medium light-splitting film 501, the front surface of the first lens 502 facing the object surface 50 is concave, and the image-facing surface 507 is convex.
  • the curvature of the front surface of the lens 502 is the same.
  • the incident light reflected by the coating on the front surface of the first lens 502 is not imaged.
  • the other part of the transmitted light passes through the first lens 502 and its rear surface and irradiates the front of the second lens 505.
  • the back surface of the first lens 502 is concave facing the object surface 50, the image surface 507 is convex, the front surface of the second lens 505 is concave facing the object surface 50, and the image surface 507 is convex; the light passes through the second lens 505
  • the front surface of the lens is irradiated to the back surface of the second lens 505 coated with the second semi-transparent and semi-reflective optical medium spectroscopic film 506.
  • the back surface of the second lens 505 is concave facing the object surface 50, and the image facing surface 507 is convex.
  • the second lens The curvature of the optical coating on the back surface of the second lens 505 is the same as the curvature of the back surface of the second lens 505; the light reflected by the second transflective optical medium splitting film 506 on the back surface of the second lens 505 enters the optical system again and passes through the second lens The light scattering of the optical film on the rear surface of the lens 505 irradiates the image surface 507.
  • the light that enters the optical system again is focused by the second lens 505, enters the first lens 502 again, and is reflected by the first semi-transparent and semi-reflective optical medium splitting film 501 on the front surface of the first lens 502, and finally focused and illuminated To the image plane 507; therefore, the image plane 507 has the scattered light transmitted for the first time, and at the same time has the focused refractive reflected light, but because the intensity of the focused light is much greater than that of the scattered light, the image plane 507 It can produce high-definition and high-quality microscopic images with high signal-to-noise ratio.
  • the light component on the image plane 507 is divergent, completely transmitted light without a focal point, and convergent multiple reflected light that forms an imaging focal point.
  • the irradiation of multiple reflected light is much higher than that of one Completely transmitted light.
  • completely transmitted light is noise
  • multiple reflected light is imaging. Therefore, the signal-to-noise ratio of imaging contrast noise is high. Even if there is completely transmitted light, it will not have a major impact on clear imaging.
  • the aforementioned first lens 502 and second lens 505 may both be circular lenses. There is an interval between the first lens 502 and the second lens 505. The interval can be filled with air or liquid, or there are other lenses and other lens combinations in the interval.
  • the front surface and the rear surface of the first lens 502 may both have aspherical surfaces, and the front surface and the rear surface of the second lens 505 may both be aspherical.
  • Table 1 shows the above-mentioned embodiment: the specific design parameter values of each lens surface and the semi-transparent and semi-reflective optical medium spectroscopic film in the optical system of the microscope objective lens 1.
  • Table 1 shows the design parameters of the microscope objective optical system of the present invention.
  • FIG. 10 shows the modulation transfer function MTF of the microscope objective optical system of this embodiment, which is close to the diffraction limit.
  • FIG. 11 shows the light characteristics of the longitudinal section of the optical system of this embodiment
  • FIG. 12 shows the light characteristics of the cross section of the optical system of this embodiment.
  • FIG. 13 shows the optical path characteristic diagram of the longitudinal section of the optical system of this embodiment
  • FIG. 14 shows the optical path characteristic diagram of the cross section of the optical system of this embodiment.
  • Fig. 15 shows a spot diagram of the optical system of this embodiment.
  • FIG. 16 shows a field curvature diagram of the optical system of this embodiment
  • FIG. 17 shows a distortion diagram of the optical system of this embodiment.
  • the number of the aforementioned micro-illumination devices 3 may be multiple, and they are arranged in sequence to form an array of micro-illumination devices.
  • the number of microscopic objective lenses 1 and the number of microscopic illuminators 3 are equal and correspond to each other to form an objective lens array.
  • each first lens 502 is arranged in sequence to form a first lens array
  • each second lens 505 is arranged in sequence to form a second lens array.
  • the number of the aforementioned digital image sensors 2 is equal to the number of the microscope objective lens 1, and corresponds to each other to form a sensor array.
  • the first lens array and the second lens array form a new objective lens array, which can simultaneously perform microscopic imaging of multiple tissue regions in close proximity, effectively realizing efficient pathological tissue chip observation and diagnosis, and high-speed digital pathological scanning.
  • a plurality of microscopic lighting devices 3 are arranged in sequence to form a microscopic lighting device array, which can meet the lighting requirements of the microscopic objective lens 1 array, and the illumination is more uniform.
  • the present invention may further include a connecting plate 106, and the optical cavities 102 of the aforementioned micro-illumination devices 3 may be arranged on the connecting plate 106 in sequence. Specifically, a plurality of through holes penetrating through both ends may be sequentially spaced on the connecting plate 106, wherein each through hole is an optical cavity 102. Each Mie scattering device 103 is sleeved in the corresponding optical cavity 102 in a one-to-one correspondence.
  • the connecting plate 106 is provided to facilitate fixing of the Mie scattering devices 103, so that the Mie scattering devices 103 form a whole.
  • the images formed by each digital image sensor 2 are arranged in the second direction in sequence without intervals; the first direction and the second direction
  • the two directions are perpendicular.
  • the first direction may be the X direction in FIGS. 1 and 2
  • the second direction may be the Y direction in FIGS. 1 and 2.
  • the microscopic objective lenses 1 corresponding to the digital image sensors 2 are also arranged in an array. Because each microscopic objective lens 1 and the digital image sensor 2 are kept relatively fixed in a one-to-one correspondence, the objective lens array formed by the microscopic objective lens 1 will move synchronously when the sensor array moves.
  • the sensor array and the microscope objective lens 1 array move together in the first direction, such as moving in the X direction in Fig. 1 and Fig. 2, each microscope objective lens 1 in the microscope objective lens 1 array simultaneously scans each part of the tissue slice , So that the images formed by the digital image sensors 2 are arranged in a second direction, such as the Y direction, without intervals.
  • each microscopic objective lens 1 corresponds to the digital image sensor 2 one-to-one
  • the arrangement and method of the array formed by each microscopic objective lens 1 and the sensor array are consistent.
  • Those skilled in the art can infer the arrangement of the microscope objective lens 1 array based on the arrangement of the sensor array.
  • the digital image sensors 2 in the sensor array may have a variety of different arrangements, for example, they may be arranged in an inclined line or in a zigzag arrangement.
  • the sensor array may have N parallel and spaced rows along the first direction.
  • N is an integer greater than or equal to 2.
  • two adjacent rows are respectively the N1th row and the N2th row along the first direction.
  • N2 N1+1, N1 is an integer greater than or equal to 1.
  • the N2th row is offset from the N1th row by a distance of FoV along the second direction.
  • FoV is the size of the image formed by the digital image sensor 2 in the second direction.
  • the sensor array sequentially has a first row, a second row, a third row, a fourth row, a fifth row, and a sixth row along the X direction.
  • the second row is offset from the first row by a distance of FoV in the Y direction.
  • the third row is offset from the second row by FoV in the Y direction.
  • the fourth row is offset from the third row by FoV in the Y direction.
  • the fifth row is offset from the fourth row by FoV in the Y direction.
  • Row 6 is offset from row 5 by FoV in the Y direction.
  • the sensor array has N parallel and spaced rows along the first direction.
  • N is an integer greater than or equal to 3.
  • the number of digital image sensors 2 located in the two outermost rows in the sensor array is equal, and they are all M1.
  • the two adjacent rows are respectively the N1th row and the N2th row along the first direction.
  • the N2th row is offset from the N1th row in the second direction by a distance of FoV; when N2 is equal to N, the N2th row protrudes from the N1th row in the second direction by a distance of FoV; FoV is the size of the image formed by the digital image sensor 2 in the second direction.
  • the sensor array sequentially has a first row, a second row, a third row, a fourth row, a fifth row, and a sixth row along the X direction.
  • the number of digital image sensors 2 is the same in the first row and the sixth row, and the numbers of the digital image sensors 2 in the fourth row to the fifth row are the same.
  • the number of digital image sensors 2 in the first row is one more than the number of digital image sensors 2 in the second row.
  • the second row is offset from the first row by a distance of FoV in the Y direction.
  • the third row is offset from the second row by FoV in the Y direction.
  • the fourth row is offset from the third row by FoV in the Y direction.
  • the fifth row is offset from the fourth row by FoV in the Y direction.
  • the 6th row protrudes FoV in the Y direction relative to the 5th row.
  • the number of digital image sensors 2 in each row described above may be two or more, and they may be arranged in sequence along the second direction.
  • the distance between two adjacent digital image sensors 2 in each row in the second direction is equal, and both are r1. This can make the structure of the sensor array more compact and smaller.
  • the corresponding arrangement parameters of the aforementioned sensor array can be obtained using the following formula.
  • N is the smallest integer greater than or equal to (W+r)/FoV.
  • r1 N*FoV-W.
  • W is the size of the digital image sensor 2 along the second direction; r is the smallest distance that can be achieved in the second direction by the processing technology of two adjacent digital image sensors 2 in the same row.
  • r2 is the smallest distance that can be achieved in the first direction by the processing technology of the digital image sensor 2 in the two adjacent rows.
  • the arrangement parameters calculated by the above formula can make the sensor array have the smallest arrangement structure.
  • the volume of the sensor array arranged by the above method is small, and each digital image in the sensor array
  • the effective utilization of sensor 2 is relatively high.
  • FoV can be obtained through image measurement of the digital image sensor 2.
  • W can be obtained by measuring the size of the digital image sensor 2.
  • r can be obtained through process evaluation.
  • the following is a specific example of the sensor array adopting a zigzag arrangement.
  • a digital image sensor 2 array the size of the digital image sensor 2 is as follows: width W is 5.18 mm, height H is 5.4 mm.
  • the imaging range FoV is 1.0 mm.
  • the digital image sensor 2 binding and packaging process stipulates that the minimum horizontal distance r is 0.8 mm, and the minimum vertical distance r2 is 0.82 mm.
  • the specific number of digital image sensors 2 in each row can be determined according to actual conditions, and the details are not repeated here.
  • a digital image sensor 2 array the dimensions of the digital image sensor 2 are as follows: the width W is 8.5 mm, and the height H is 8.5 mm.
  • the imaging range FoV is 1.0 mm.
  • the digital image sensor 2 binding and packaging process stipulates that the minimum horizontal distance r is 0.3 mm, and the minimum vertical distance r2 is 0.3 mm.
  • the specific number of digital image sensors 2 in each row can be determined according to actual conditions, and the details are not repeated here.
  • the digital pathological imaging device of the present invention further includes a fixing plate 61, and the fixing plate 61 is provided with a mounting hole 62.
  • the number of mounting holes 62 is equal to the number of microscope objective lenses 1 and corresponds to each other; each microscope objective lens 1 is mounted in the corresponding mounting hole 62 one to one, and the first lens 502 is located at one end of the mounting hole 62.
  • the second lens 505 is located at the other end of the mounting hole 62.
  • the multiple mounting holes 62 on the fixing plate 61 are arranged in the same array as the microscopic objective lens 1, and after each microscopic objective lens 1 is installed in the corresponding mounting hole 62 in a one-to-one correspondence, the alignment can be realized.
  • the microscopic objective lens 1 arranged in an array is fixed.
  • a plurality of traditional brackets are integrated together to form an integrated fixed bracket with array mounting holes 62 (ie, fixing plate 61), which reduces the wall thickness of the traditional bracket and realizes the array type Integrated fixation of the microscope objective lens 1.
  • the outer diameter of the aforementioned first lens 502 is smaller than the outer diameter of the second lens 505.
  • the mounting hole 62 includes a first hole section 601, a second hole section 602, and a third hole section 603 connected in sequence. The outer diameters of the first hole section 601, the second hole section 602, and the third hole section 603 decrease in order.
  • the first lens 502 is fixed on the first hole section 601 and the second lens 505 is fixed on the third hole section 603.
  • the lengths of the first hole section 601 and the third hole section 603 are relatively short, and both of them are mainly used for fixing the first lens 502 and the second lens 505.
  • the light emitted from the first lens 502 can pass through the second hole section 602 and illuminate the second lens 505.
  • the side wall of the first hole section 601 may be provided with a first notch 621, and the first notch 621 is filled with a light adhesive 64.
  • the aforementioned first lens 502 is fixed on the first hole section 601 by the optical adhesive 64.
  • the number of the first notches 621 may be more than two, and they are evenly distributed in a circular shape around the first hole section 601. In a specific application example, the number of the first notches 621 is four.
  • the side wall of the aforementioned third hole section 603 may be provided with a second notch 622, and the second notch 622 is filled with a light adhesive 64.
  • the aforementioned second lens 505 is fixed on the third hole section 603 by the optical adhesive 64.
  • the number of the second notches 622 can be more than two, and they are evenly distributed around the third hole section 603 in a circular shape. In a specific application example, the number of second notches 622 is four.
  • first notch 621 is provided on the side wall of the first hole section 601 and a second notch 622 is provided on the side wall of the second hole section 602
  • first notch 621 It may be located at an end of the first hole section 601 close to the second hole section 602 and the second gap 622 is located at an end of the third hole section 603 away from the second hole section 602.
  • this is beneficial to improve the appearance of the light incident side of the fixed bracket.
  • the aforementioned second hole section 602 may have a frustum shape, and the center line of the second hole section 602 coincides with the center line of the first lens 502 or the second lens 505. Because the light emitted from the first lens 502 radiates to the second lens 505 in a conical shape, the shape of the second hole section 602 is set to be consistent with the shape of the light column of the first lens 502, which saves the space of the fixing bracket The effect of this is that the outer diameter of the second hole section 602 is not too large to affect the structural strength of the fixing bracket.
  • the digital pathological imaging device of the present invention may also include an image data acquisition controller 7, a data bus interface 8, a random access memory 9, a central processing unit 10, a non-volatile memory 11, and a display output port. 12.
  • the digital image sensor 2 is connected to the image data acquisition controller 7 through a parallel data interface.
  • the image data acquisition controller 7 is used to read the digital image data transmitted by the digital image sensor 2; the image data acquisition controller 7 and the random access memory 9 The connection is made through the data bus interface 8.
  • the image data acquisition controller 7 transmits the digital image data to the RAM 9 through the data bus interface 8.
  • the central processing unit 10 and the RAM 9, the non-volatile memory 11 and the display output port 12 pass the circuit Bus connection, the central processing unit 10 is used to read the digital image data in the random access memory 9, store the digital image data in the non-volatile memory 11, and output to the display output port 12 for image data display.
  • the aforementioned digital image sensor 2 may be a sensor that has photoelectric conversion and generates digital signals.
  • Both the image data acquisition controller 7 and the central processing unit 10 may be a processor chip or electronic system with serial calculation and logic processing, or a processor chip or electronic system with parallel calculation and logic processing.
  • the image data acquisition controller 7 and the central processing unit 10 can be a field programmable gate array or a central processing unit.
  • the aforementioned image data acquisition controller 7 is used to receive the method or communication protocol of the image acquisition device in parallel or serially to collect and process image data.
  • the image data acquisition controller 7 also uses a serial or parallel data calculation method to pre-process the image data.
  • the serial or parallel data calculation method may be an image data format conversion calculation method, and/or an image data compression calculation method, and/or an image color adjustment calculation method.
  • the central processing unit 10 is used to read the data stored in the random access memory 9 and write the data read in the random access memory 9 into the display output port 12 in a direct memory access manner.
  • the aforementioned data bus interface 8 may be a data bus and hardware interface from the image data acquisition controller 7 to the random access memory 9.
  • the data bus interface 8 is a PCI-express bus and interface, or a USB bus and interface, or a parallel transmission bus and interface.
  • the aforementioned random access memory 9 may be a register with data buffer access.
  • the random access memory 9 is a pre-stored buffer, or a double data rate random access memory, or a double data rate synchronous dynamic random access memory. The random access memory 9 is used to write the read bus interface data in a direct memory access manner.
  • the aforementioned non-volatile memory 11 may be a computer memory that does not disappear after the power is turned off.
  • the non-volatile memory 11 is a read-only memory, or a magnetic disk memory, or a solid hard disk memory.
  • the non-volatile memory 11 is used to read data stored in the random access memory 9 and write the read data to the random access memory 9 in a direct memory access manner.
  • the invention is a computer-oriented method for collecting, transmitting, displaying, and storing large-scale image data.
  • the large-scale digital image data transmitted from multiple digital image acquisition devices such as digital cameras or digital scanners are uploaded to digital image processing at high speed.
  • the system also uses real-time display and high-speed storage to solve the problems of traditional data transmission methods that cannot achieve short-time high-speed transmission and slow display of digital image big data.
  • a high-speed transmission method of large-scale digital image data is a new high-speed data transmission technology for high-speed transmission, display and storage of digital image big data.
  • the image data acquisition controller 7 reads data from the digital image sensor 2, and the image data is preprocessed by the data processing unit integrated in the image data acquisition controller 7 for color adjustment, data format conversion, and data compression.
  • the image big data is sent to the data transmission bus;
  • the control program running on the central processing unit 10 switches the control of the central processing unit 10 and the bus controller to the data transmission bus, and the big data read to the data transmission bus is passed through
  • the direct memory access method is written into the random access memory 9.
  • the control program will transfer the control of the data transmission bus back to the central processing unit 10 by the bus controller.
  • the random access memory The data in 9 is directly written into the data display port. While the image data is displayed, the background automatically writes the image big data into the non-volatile memory 11 by direct memory access to realize the high-speed image display and display of digital image big data.
  • Non-volatile storage Non-volatile storage.
  • the data transmission speed on the data bus and the data transmission speed of the RAM 9 are the smallest The value determines the maximum data transmission speed of the present invention.
  • the maximum transmission speed is 252Gbit/s.
  • the random access memory 9 adopts DDR4 SDRAM PC4-34100
  • the maximum transmission speed is 272.8Gbit /s. Therefore, in this case, the highest transmission speed of the present invention is 252Gbit/s.
  • the shortest transmission time is about 0.13 seconds, which meets the needs of real-time data transmission. .
  • the central processing unit 10 when data is transmitted to the display output port 12, the central processing unit 10 directly reads the data in the RAM 9 and sends it to the display output port 12. Therefore, the data transmission speed of the RAM 9 is the same as that of the display output port 12.
  • the minimum transmission speed determines the maximum display output speed of the present invention.
  • the RAM 9 uses DDR4 SDRAM PC4-34100
  • the maximum transmission speed is 272.8Gbit/s
  • the display output port 12 uses the HDMI2.1 interface protocol
  • the highest transmission speed is 48Gbit/s. Therefore, in this case, the highest display output speed of the present invention is 48Gbit/s.
  • the shortest transmission time is about 0.7 Seconds, in line with the needs of high-speed data display.
  • the central processing unit 10 directly reads the data in the RAM 9 and sends it to the display output port 12, it also sends the data to the non-volatile memory 11 through the data bus, so the data transmission of the RAM 9
  • the minimum speed and the data transmission speed of the nonvolatile memory 11 determine the maximum data storage speed of the present invention.
  • the maximum transmission speed is 272.8Gbit/s.
  • the maximum transmission speed is 6Gbit/s.
  • the maximum data storage speed of the present invention is 6Gbit/s, and the data volume is about 32Gbit
  • the shortest storage time is about 5.3 seconds. After the digital image output is displayed, users usually need to observe, especially in the process of digital pathology diagnosis, for the observation and diagnosis of digital pathology images.
  • the time is at least 20 seconds (the shortest time for general pathological diagnosis), so the data storage time of the present invention meets the needs of high-speed data storage.

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Abstract

一种数字化病理成像设备，该数字化病理成像设备包括显微照明装置（3）、显微物镜（1）和数字图像传感器（2）；显微照明装置（3）包括光源（101）、米氏散射器件（103）、光学腔（102）和聚光镜（105）；光源（101）位于米氏散射器件（103）的一侧，聚光镜（105）位于米氏散射器件（103）的另一侧，光源（101）用于发出光照射到米氏散射器件（103）上；米氏散射器件（103）用于将光源（101）射入的光发散照射到聚光镜（105）上；聚光镜（105）用于将米氏散射器件（103）射入的光聚焦输出到被测体上；显微物镜（1）包括沿光轴方向依次设置的第一透镜（502）和第二透镜（505），第一透镜（502）用于接收从被测体射入的光；第一透镜（502）前表面和第二透镜（505）后表面均镀有半透半反光学介质分光薄膜；数字图像传感器（2）用于接收从第二透镜（505）射入的光，并进行数字成像。

Description

一种数字化病理成像设备 技术领域
本发明涉及光学成像技术领域，特别涉及一种数字化病理成像设备。
背景技术
数字化病理是指将计算机和网络应用于了病理学领域，是一种现代数字系统与传统光学放大装置有机结合的技术。其主要采用数字病理成像设备对切片组织进行扫描。
现有的数字病理成像设备一般包括显微物镜和光源系统。其光源照射出来的光通常呈高斯分布，显微视野中央区域亮度最高，四周亮度较低，这种光照不均的问题，在数字显微镜中体现为数字图像呈现明暗照度不均，特别是数字病理全切片成像领域，多个显微视野的数字图像需要拼接，光照不均则导致拼接后的数字病理图像中存在明暗波动，必须通过数字图像亮度调整算法进行补偿，否则造成诊断医生的视觉疲劳，降低诊断效率与诊断精度。通常，数字病理图像尺寸较大，对于这样的大数据进行亮度补偿，计算效率低下，导致数字病理成像整体耗时较大。
另外，现有的显微物镜一般由入瞳透镜，孔径光阑，中间透镜或中间透镜组合，以及出瞳透镜组成，作用是将本观测物体的局部区域进行放大，以实现人们对微观世界的观察。来自被观测物体的光线，首先通过入瞳透镜，照射入镜筒之中，其次在孔径光阑和中间透镜的作用下被放大，最后通过出瞳透镜照射到镜筒之外，并实现清晰的成像。
显微物镜的性能主要由：数值孔径、视野范围、放大倍数、有效焦距。数值孔径描述了物镜收光锥角的大小，直接决定显微物镜的收光能力以及光学分辨率，例如：数值孔径越大，显微物镜收光能力越强，光学分辨率越高；视野范围是显微物镜所能够放大成像的观测物体范围，放大倍数是视野范围与成像面积的比例，通常在成像面积固定的情况下，放大倍数越大，视野范围越小，所需要的中间透镜数量越多(通常大于三片透镜)，以抑制高倍率成像的像差；有效焦距是光学系统的主点到焦点在光轴上的距离，有效焦距越小，放大倍数越大，视野范围越小，数值孔径越大。
对于光学显微镜使用者来说，理想的显微物镜具备特点：较大视野范围、较大数值孔径，以实现一次性即可观察到被观测物体超微结构的全部细节，提高显微观察效率，减少观察负担。然而，根据上述决定显微物镜性能的各参数之间关系可知，对超微结构的清晰成像，势必需要增大数值孔径以及放大倍数，这必然导致视野范围的缩小，中间透镜数量增多，显微物镜的体积和制作生产成本和装配难度骤增。
上述的传统显微物镜中存在的限制，导致在实际应用中，为光学显微镜使用者带来诸多不变。例如，在病理诊断领域，医生每天要承担100张以上的病理切片显微观察任务，使用传统显微物镜，由于数值孔径和放大倍数的限制，医生在观察每一张切片时都需要反复切换不同倍率的显微物镜，以实现对病理切片从宏观到超微结构的精确观察，保证病理诊断的精准；由于视野范围的限制，医生在进行显微观察时必须操作平移载物台，以实现对整个切片中每一个局部组织的观察和诊断，防止误诊和漏诊；上述说明传统显微镜性能上的限制，导致光学显微镜使用复杂度加大，医生观察一张病理切片通常需要20分钟以上，效率极低，面对巨大的诊断工作量，病理医生的劳动负担以及强度巨大，不仅威胁着病理医生身心健康，同时也为病理诊断的漏诊和误诊增大了风险。另一方面，由于显微物镜体积大，导致光学显微镜体积大，不利于其在面积受限的病理科进行大量放置，同时高昂的价格，不利于医院的采购，也导致了病理诊断医疗费用的增加。
由于上述光源系统和显微物镜的缺陷，导致数字病理技术虽然能够在一定程度上减轻病理医生的负担和劳 动强度，提升病理诊断精准度，但是，病理诊断的效率仍然没有得到改善，甚至比传统的病理诊断效率更加低下，这严重限制了数字病理技术的发展及其在临床中的应用。
发明内容
有鉴于此，本发明提供一种数字化病理成像设备，主要目的在于使其光源发出的光更加均匀，并且显微物镜的数值孔径、视野范围都足够大的同时体积更小、成本更低。
为达到上述目的，本发明主要提供如下技术方案：
本发明的实施例提供一种数字化病理成像设备，包括显微照明装置、显微物镜和数字图像传感器；
所述显微照明装置包括光源、米氏散射器件、光学腔和聚光镜；光源位于米氏散射器件的一侧，聚光镜位于米氏散射器件的另一侧，所述米氏散射器件套设在光学腔内；光源用于发出光照射到米氏散射器件上；米氏散射器件用于将光源射入的光发散照射到聚光镜上；聚光镜用于将米氏散射器件射入的光聚焦输出到第一透镜上；
所述显微物镜包括沿光轴方向依次设置的第一透镜和第二透镜，所述显微物镜通过第一透镜接收从被测体射入的光；第一透镜面向物面的表面为前表面，面向像面的表面为后表面；第二透镜面向物面的表面为前表面，面向像面的表面为后表面；第一透镜前表面镀有第一半透半反光学介质分光薄膜，第二透镜后表面镀有第二半透半反光学介质分光薄膜；
所述数字图像传感器用于接收从第二透镜射入的光，并进行数字成像。
本发明进一步设置为：所述显微照明装置的数量为多个、且依次排布形成显微照明装置阵列；
所述显微物镜的数量与所述显微照明装置的数量相等、且一一对应，以形成物镜阵列；
所述数字图像传感器的数量与所述显微物镜的数量相等、且一一对应，以形成传感器阵列。
本发明进一步设置为：所述传感器阵列用于沿第一方向运动时，各数字图像传感器所成的像在第二方向上依次无间隔排布；所述第一方向与第二方向垂直。
本发明进一步设置为：所述传感器阵列沿第一方向具有N个平行间隔排布的行，N为大于或等于2的整数；
其中，相邻的两行沿第一方向分别为第N1行和第N2行，N2＝N1+1，N1为大于或等于1的整数；第N2行沿第二方向相对第N1行偏移大小为FoV的距离，FoV为数字图像传感器所成的像在第二方向上的尺寸大小。
本发明进一步设置为：所述传感器阵列沿第一方向具有N个平行间隔排布的行，N为大于或等于3的整数；传感器阵列中位于最外侧两行的数字图像传感器的数量相等、且均为M1个，其它行的数字图像传感器的数量为M2个，M1＝M2+1；
其中，相邻的两行沿第一方向分别为第N1行和第N2行，N2＝N1+1，N1为大于或等于1的整数；当N2小于N时，第N2行沿第二方向相对第N1行偏移大小为FoV的距离；当N2等于N时，第N2行沿第二方向相对第N1行凸出大小为FoV的距离；FoV为数字图像传感器所成的像在第二方向上的尺寸大小。
本发明进一步设置为：各行内数字图像传感器的数量均为两个以上、且沿第二方向依次排布；
各行内相邻两数字图像传感器在第二方向上的距离相等、且均为r1。
本发明进一步设置为：N为大于或等于(W+r)/FoV的最小整数；
r1＝N*FoV-W；
其中，W为数字传感器沿第二方向的尺寸大小；r为同一行内相邻两数字图像传感器的加工工艺在第二方向上所能实现的最小间隔。
本发明进一步设置为：相邻两行在第一方向上的间隔为r2，r2为相邻两行内的数字图像传感器的加工工艺在第一方向上所能实现的最小间隔。
本发明进一步设置为：数字化病理成像设备还包括固定板，所述固定板上设有安装孔；
所述安装孔的数量与显微物镜的数量相等、且一一对应；各所述显微物镜一一对应地安装在相应的安装孔内，且第一透镜位于安装孔的一端，第二透镜位于安装孔的另一端。
本发明进一步设置为：所述第一透镜的外径小于所述第二透镜的外径；
所述安装孔包括依次连接的第一孔段、第二孔段和第三孔段，所述第一孔段、第二孔段和第三孔段三者的外径依次减小；
其中，所述第一透镜固定在所述第一孔段上，所述第二透镜固定在第三孔段上。
本发明进一步设置为：所述第一孔段的侧壁上设有第一缺口，所述第一缺口内填充有光粘胶剂，所述第一透镜通过所述光粘胶剂固定在所述第一孔段上；
和/或，所述第三孔段的侧壁上设有第二缺口，所述第二缺口内填充有光粘胶剂，所述第二透镜通过所述光粘胶剂固定在所述第三孔段上。
本发明进一步设置为：当第一孔段的侧壁上设有第一缺口、且第三孔段的侧壁上设有第二缺口时，所述第一缺口位于第一孔段的靠近第二孔段的一端，所述第二缺口位于所述第三孔段的背离第二孔段的一端。
本发明进一步设置为：所述第二孔段呈锥台形，所述第二孔段的中心线与第一透镜或第二透镜的中心线重合。
本发明进一步设置为：所述光源为发光二极管，或者半导体激光器。
本发明进一步设置为：所述米氏散射器件，是一种分布着米氏散射介质粒子的固体光学器件，该光学器件为透明，或者半透明，光学器件的折射率小于米氏散射介质粒子的折射率。
本发明进一步设置为：所述光学腔，是包裹在米氏散射器件外部的两端开口的中空筒状封闭腔，其内壁为反射光的镜面，或者黑色氧化层表面。
本发明进一步设置为：所述聚光镜，是一种能够将均匀光传播方向进行收缩，进行聚光照射的光学透镜或者光学透镜组合。
本发明进一步设置为：所述光源通过光学胶粘接固定在米氏散射器件的一侧，聚光镜通过光学胶粘接固定在米氏散射器件的另一侧。
本发明进一步设置为：第一透镜和第二透镜是圆形透镜，第一透镜和第二透镜之间具有间隔；间隔中充满空气或者液体，又或者间隔内设有其他透镜及其他透镜组合。
本发明进一步设置为：第一透镜的前表面和后表面的面型为非球面，第二透镜的前表面和后表面为非球面。
本发明进一步设置为：数字化病理成像设备还包括图像数据采集控制器、数据总线接口、随机存储器、中央处理器、非易失性存储器和显示输出端口；
其中，数字图像传感器通过并行数据接口与图像数据采集控制器相连，图像数据采集控制器用于读取数字图像传感器传输来的数字图像数据；图像数据采集控制器与随机存储器通过数据总线接口进行连接，图像数据采集控制器通过数据总线接口向随机存储器传送数字图像数据；中央处理器与随机存储器、非易失性存储器以及显示输出端口通过电路总线连接，中央处理器用于读取随机存储器中的数字图像数据，将数字图像数据存储入非易失性存储器中，同时输出到显示输出端口用于图像数据显示。
本发明进一步设置为：图像数据采集控制器以及中央处理器为具有串行计算及逻辑处理的处理器芯片或电子系统、或者具有并行计算及逻辑处理的处理器芯片或电子系统、又或者兼具串行以及并行计算及逻辑处理的处理器芯片或电子系统。
本发明进一步设置为：数据总线接口为从图像数据采集控制器到随机存储器之间的数据总线及硬件接口。
本发明进一步设置为：随机存储器为具有数据缓冲存取的寄存器；和/或，非易失性存储器为电源关闭后， 所存储的数据不会消失的计算机存储器。
本发明进一步设置为：图像数据采集控制器用于并行或者串行接收数字图像传感器的方法或者通信协议，以对图像数据采集处理，并采用串行或者并行数据处理算法，对图像数据进行预先处理。
本发明进一步设置为：随机存储器用于以直接存储器访问的方式将读取的总线接口数据写入。
本发明进一步设置为：中央处理器用于将随机存储器中存储的数据进行读取，以直接存储器访问的方式将随机存储器中读取的数据写入显示输出端口。
本发明进一步设置为：非易失性存储器用于将随机存储器中存储的数据进行读取，以直接存储器访问的方式将读取的随机存储器数据写入。
借由上述技术方案，本发明数字化病理成像设备至少具有以下有益效果：
(1)显微照明装置所输出的白色光，光照均匀，光谱分布均匀，传统显微光源照明光亮呈高斯分布，不同照明的光谱分布不一定相同；显微照明装置能够保证较高光源利用率，传统光源体积大，且不能保证光源利用率；显微照明装置的结构简单且装配简单，实现聚焦照射，仅需要一枚光学镜头，传统光源需要多枚透镜组合才能实现照射相对均匀的光源；光源采用发光二极管，功耗低、价格便宜，且能够持续使用5万小时以上，因此，相对于传统光源，本发明稳定、可靠，使用时间长。
(2)本发明的显微物镜采用折反射式结构，不仅能够以极少的透镜数量实现高性能的光学显微物镜，而且增长了光线在光学系统中传播的路径长度，使显微物镜达到了其所能的衍射极限，将两片透镜的光学性能发挥到极致；本发明的显微物镜由于在保证高性能的同时减少了透镜的数量，带来物镜体积的极大减少，生产成本的极大节省，以及生产难度的极大降低；本发明的显微物镜能够实现成像光的汇聚，形成高能量成像焦点，极大提升成像的信噪比，实现在一个大的显微视野内的高质量清晰成像；本发明的显微物镜完全满足光学显微镜的小型化需求，特别地，完全满足数字病理高速扫描的需求，能够将传统的数字病理扫描时间提升10倍以上，完全满足数字病理技术在临床病理诊断中的高效与精准的应用需求。
(3)第一透镜阵列与第二透镜阵列组成新型物镜阵列，能够对位置相近的多个组织区域进行同时的显微成像，有效实现高效的病理组织芯片观察与诊断、高速数字病理扫描。
(4)由多个显微照明装置依次排布形成显微照明装置阵列，可以满足显微物镜阵列的照明需求，且光照更加均匀。
(5)通过在固定板上设置多个安装孔，该多个安装孔呈与显微物镜相同的阵列排布，各显微物镜可以一一对应地安装在相应的安装孔内，从而可以对呈阵列排布的显微物镜进行固定。
(6)现有技术中，中央处理器首先接收USB等外部设备接口传输来的图像数据，其次将数据写入随机存储器，然后读取随机存储器内的数据，将其送入显示输出端口，在显示结束后，数据停留在显示缓存，中央处理器再将随机存储器内的数据通过总线传输到非易失性存储器中。这个过程由中央处理器进行控制，通常造成数据传输缓慢，通常需要10秒以上，甚至数分钟的时间，例如当中断处理任务发生时，中央处理器需要暂停当前数据传输任务，中断处理任务结束后，中央处理器需要回复数据传输任务，过多的中断处理任务可导致数据传输速度降低。
本发明的方法，数据传输过程没有中央处理器的干预，控制程序控制中央处理器将数据总线控制权切换到总线控制器，从而实现数据从总线直接对随机存储器的传输，此情况下，数据传输属于端到端的传输，不存在中断，且总线传输速度大，能够实现更加高速的数据传输。
另外，本发明的方法，用于显示的数据传输与面向非易失性存储器的数据传输属于并发性数据传输，二者同时进行，且属于直接存储器读取与数据传输，因此数据速度的上限被限制在显示端口以及非易失性存储器速度，充分发挥数据总线传输优势，使数据传输速度达到极限。
上述说明仅是本发明技术方案的概述，为了能够更清楚了解本发明的技术手段，并可依照说明书的内容予以实施，以下以本发明的较佳实施例并配合附图详细说明如后。
附图说明
图1是本发明的一实施例提供的一种数字化病理成像设备的结构简图；
图2为本发明提供的一种显微照明装置的结构示意图；
图3为图2中显微照明装置的光路示意图；
图4为本发明的显微照明装置在数字病理显微成像中的应用示意图；
图5为使用本发明显微照明装置照明时的显微图像；
图6为使用传统显微照明装置照明时的显微图像；
图7为本发明的显微物镜的结构及光路图；
图8为本发明显微物镜的第一透镜的结构图；
图9为本发明显微物镜的第二透镜的结构图；
图10为本发明显微物镜光学系统的调制传递函数MTF图；
图11为本发明显微物镜光学系统的纵截面的光线特性光扇图；
图12为本发明显微物镜光学系统的横截面的光线特性光扇图；
图13为本发明显微物镜光学系统的纵截面的光程光扇图；
图14为本发明显微物镜光学系统的横截面的光程光扇图；
图15为本发明显微物镜光学系统的点列图；
图16为本发明显微物镜光学系统的视场场曲图；
图17为本发明显微物镜光学系统的畸变图；
图18为本发明提供的一种显微照明装置阵列的结构示意图；
图19为本发明显微物镜阵列的截面图；
图20为本发明显微物镜阵列的成像示意图；
图21是本发明的一实施例提供的一种显微物镜与数字图像传感器两者组合的阵列排布方式；
图22是本发明的另一实施例提供的一种显微物镜与数字图像传感器两者组合的阵列排布方式；
图23是本发明的一实施例提供的一种数字图像传感器的阵列排布方式；
图24是本发明的另一实施例提供的一种数字图像传感器的阵列排布方式；
图25是本发明的一实施例提供的一种固定板的结构示意图；
图26是本发明的一实施例提供的一种显微物镜安装在固定板上的剖面结构示意图；
图27为本发明数字化病理成像设备的数字图像大数据高速传输的硬件实现结构与数据处理流程图；
图28为本发明数字化病理成像设备的数字图像大数据高速传输的硬件实现结构图。
附图标记：1、显微物镜；2、数字图像传感器；3、显微照明装置；101、光源；102、光学腔；103、米氏散射器件；104、米氏散射介质粒子；105、聚光镜；106、连接板；201、光源发出的光；202、经过米氏散射介质粒子散射的光；203、散射光照射到光学腔壁上进行反射的光；204、通过米氏散射器件射出的光；205、通过聚光镜汇聚的光；206、汇聚光形成的光照面；301、微型LED发光芯片；302、UV固化光学粘合胶；303、米氏散射微棒；304、纳米微球；305、透明聚碳酸酯；306、镜筒；307、平凸透镜；308、出射光线；309、载玻片；310、被观测细胞；311、盖玻片；402、使用传统照明时图像中心亮；403、使用传统照明时图像四周暗；50、物面；501、第一半透半反光学介质分光薄膜；502、第一透镜；503、第一透镜后表面；504、第二透镜前表面；505、第二透 镜；506、第二半透半反光学介质分光薄膜；507、像面；61、固定板；62、安装孔；64、光粘胶剂；621、第一缺口；622、第二缺口；601、第一孔段；602、第二孔段；603、第三孔段；7、图像数据采集控制器；8、数据总线接口；9、随机存储器；10、中央处理器；11、非易失性存储器；12、显示输出端口。
具体实施方式
下面将结合本发明实施例中的附图，对本发明实施例中的技术方案进行清楚、完整地描述。需要说明，若本发明实施例中有涉及方向性指示(诸如上、下、左、右、前、后……)，则该方向性指示仅用于解释在某一特定姿态(如附图所示)下各部件之间的相对位置关系、运动情况等，如果该特定姿态发生改变时，则该方向性指示也相应地随之改变。另外，若本发明实施例中有涉及“第一”、“第二”等的描述，则该“第一”、“第二”等的描述仅用于描述目的，而不能理解为指示或暗示其相对重要性或者隐含指明所指示的技术特征的数量。由此，限定有“第一”、“第二”的特征可以明示或者隐含地包括至少一个该特征。
如图1所示，本发明的一个实施例提出的一种数字化病理成像设备，包括显微物镜1、数字图像传感器2和显微照明装置3。如图2所示，显微照明装置3包括光源101、米氏散射器件103、光学腔102和聚光镜105；光源101位于米氏散射器件103的一侧，聚光镜105位于米氏散射器件103的另一侧，米氏散射器件103套设在光学腔102内；光源101用于发出光照射到米氏散射器件103上；米氏散射器件103用于将光源101射入的光发散照射到聚光镜105上；聚光镜105用于将米氏散射器件103射入的光聚焦输出到被测体比如被观测细胞301上。如图7所示，显微物镜1包括沿光轴方向依次设置的第一透镜502和第二透镜505。显微物镜1通过第一透镜502接收从被测体射入的光。第一透镜502面向物面50的表面为前表面，面向像面507的表面为后表面；第二透镜505面向物面50的表面为前表面，面向像面507的表面为后表面；第一透镜502前表面镀有第一半透半反光学介质分光薄膜501，第二透镜505后表面镀有第二半透半反光学介质分光薄膜506。数字图像传感器2用于接收从第二透镜505射入的光，数字图像传感器2可以对接收的光线进行处理并转化为电信号输出，以进行数字成像。
其中，显微照明装置3的技术原理如下：如图2和图3所示，显微照明装置3的核心器件是一种充满米氏散射介质粒子104的固体光学器件，该器件为透明或半透明的固体，材质为光学树脂或光学玻璃，具有将入射光束进行均匀散射输出的性能。在米氏散射器件103的两侧，分别放置光源101以及聚光镜105。光源101可以通过光学胶粘接固定在米氏散射器件103的一侧，聚光镜105可以通过光学胶粘接固定在米氏散射器件103的另一侧。光源101一端为光束入射端，聚光镜105一端为光束输出端。为了使入射光进入米氏散射器件103后不从器件向外透射，在米氏散射器件103外侧包裹中空镜筒306(如图4所示)，为了提升光源101的光照利用率，可对镜筒306内壁进行全反射膜镀膜处理，为了进一步降低成本且光照亮度足够的情况下，可对镜筒306内壁进行黑色氧化处理。
当光源101发出的光束照射入米氏散射器件103后，由于器件内部充满介质粒子，光束遇到这些粒子会发生大量的米氏散射，这些散射的光在通过米氏散射器件103的过程中不断地进行散射与叠加，最终输出光照均匀的光。
当镜筒306内壁为全反射镀膜时，在米氏散射器件103内发生散射的光，被镜筒306内壁反射，并在期间内不断地发生散射、叠加与反射，导致光强损耗较少，米氏散射器件103输出的光强较亮。
当镜筒306内壁为黑色氧化处理时，在米氏散射期间内发生散射的光，照射到镜筒306内壁，将不反射或者反射光极弱，导致光在米氏散射器件103内传输的损耗较大，米氏散射期间输出的光强较弱。
当光源101采用彩色发光二极管时，由于二极管制作工艺原因，红色光、蓝色光、绿色光三种发光二极管不能集成于相同位置，经过聚光镜105，形成位于不同位置的三个焦点，导致显微观察出现色彩偏差。但是，基于米氏散射理论，米氏散射的程度跟波长无关，光子散射后性质保持不管，因此，经过米氏散射器件103，尽管 三种发光二极管处于不同的位置，但是仍然获得稳定的均匀白色输出，且能够通过聚光镜105，形成一个焦点。
当光源101采用白光发光二极管时，每一个二极管发出的白色光，其光谱成分均不相同，但是，基于上述米氏散射理论，经过米氏散射器件103所输出的白色光，尽管发光二极管不同，但仍能形成稳定均匀的白光输出，提升了光源101的稳定性。
图3为本发明基于米氏散射的均匀光显微照明装置3的光路示意图。其中，箭头201为光源101发出的光，箭头202为经过米氏散射介质粒子104散射的光，箭头203为散射光照射到光学腔102壁上进行反射的光，箭头204为通过米氏散射器件103射出的光，箭头205为通过聚光镜105汇聚的光，206为汇聚光形成的光照面。
上述的光源101可以为发光二极管或半导体激光器。米氏散射器件103可以是一种分布着米氏散射介质粒子104的固体光学器件。米氏散射介质粒子104分布在固体光学器件内部。该光学器件为透明，或者半透明。光学器件的折射率小于米氏散射介质粒子104的折射率。光学腔102可以是包裹在米氏散射器件103外部的两端开口的中空筒状封闭腔，其内壁为反射光的镜面，或者黑色氧化层表面。聚光镜105是一种能够将均匀光传播方向进行收缩，进行聚光照射的光学透镜或者光学透镜组合。
在一个具体的应用示例中，如图4所示，上述的光源101可以为微型LED发光芯片301，米氏散射器件103为米氏散射微棒303，光学腔102为镜筒306，聚光镜105为平凸透镜307。在该示例中，所述一种基于米氏散射的均匀光显微照明装置3包括微型LED发光芯片301、米氏散射微棒303、镜筒306、以及平凸透镜307。所述米氏散射微棒303是以透明聚碳酸酯305为基础材料，其中掺杂乳酸-羟基乙酸聚合物(PLGA)或者聚乙烯醇(PVA)为材料、直径为1-100纳米的纳米微球304的小型柱体光学器件，纳米微球304即为前述的米氏散射介质粒子104。柱体直径与LED发光部分的直径相同或近似，聚碳酸酯的折射率小于纳米微球304的折射率，纳米微球304的分布为随机分布，这样，可使入射光照射到纳米微球304，从而发生米氏散射。所述镜筒306为包裹米氏散射微棒303表面的不透光中空圆筒，其内壁具有光反射镜面镀膜，可以反射米氏散射光，以保证出射光具有较强的亮度。所述平凸透镜307是具有两个表面的一枚透镜，一个表面为平面，另一个表面为球面，将米氏散射微棒303的出射光进行汇聚，汇聚点的距离等于平凸透镜307的焦点距离。所述微型LED发光芯片301与平凸透镜307使用UV固化光学粘合胶302分别粘合在米氏散射微棒303的输入端与输出端，微型LED发光芯片301的发光表面与米氏散射微棒303的输入端表面粘合，平凸透镜307的平面表面与米氏散射微棒303的输出端粘合。
所述一种基于米氏散射的均匀光显微照明装置3的一种实施例，其使用方法是这样的：如图4所示，首先对微型LED发光芯片301通电，LED表面发光，光束在米氏散射微棒303内部发生米氏散射，以使均匀的白光从米氏散射微棒303输出，并照射在平凸透镜307的平面表面，通过平凸透镜307的折射，均匀白光即平面透镜的出射光线308被汇聚照射在平凸透镜307的焦点上。此时，如果被观测物体为组织切片上的被观测细胞310，组织切片位于载玻片309和盖玻片311之间。组织切片位置在均匀白光汇聚焦点上，均匀白光透过组织切片形成物体光，照射到光学显微镜的显微物镜1中，通过显微镜光学系统，物体光被放大并成像于数字图像传感器2上，通过计算机对数字图像传感器2数据的读取与编码，形成数字显微图像，显示在显示器上。由于照射在组织细胞上的光为均匀照射的白色光，因此在数字显微图像上，将不能观测到原始LED发出的光亮呈高斯分布的明暗不同的背景，而是背景光亮均匀的图像。
其中，图5为使用本发明一种基于米氏散射的均匀光显微照明装置3照明时的显微图像，图6为使用传统显微照明装置照明时的显微图像。图6中的402为使用传统照明时图像中心亮，403为使用传统照明时图像四周暗。通过对比图5和图6，可以看出本发明中显微照明装置3所输出的白色光，光照均匀，光谱分布均匀；而传统显微光源照明光亮呈高斯分布，光照分布不均匀。
上述的显微物镜1是一种折反射式的物镜。首先，如图7所示，沿其光轴方向，从被观测物体表面(物面50) 到成像表面(像面507)依次包括第一透镜502和第二透镜505。第一透镜502为弯月透镜，面向物面50的前表面为凹面，面向像面507的后表面为凸面。第二透镜505为凹凸透镜，面向物面50的前表面为凹面，面向像面507的后表面为凸面。第一透镜502和第二透镜505的前后表面曲率均不相同。孔径光阑位于第一透镜502的后表面位置。
如图7至图9所示，第一透镜502的前表面和第二透镜505的后表面均镀有半透半反光学介质分光薄膜。其中，半透半反光学介质分光薄膜是一种光学镀膜，能够使入射光沿入射方向透过并继续传播，同时使入射光沿入射逆方向反射并沿入射逆方向继续传播，沿入射方向透过并继续传播的光为透过光，沿入射逆方向发射并沿入射逆方向继续传播的光为反射光，根据能量守恒定律，反射光与透过光的能量总和等于入射光的能量，具体体现在反射光与透过光的光照强度的总和等于入射光的光照强度。
在一个具体的应用示例中，前述显微物镜1的具体性能参数可以为：视野范围直径为1毫米，数值孔径为0.6，有效焦距为0.78毫米，入瞳直径为1.17毫米，视野范围为1.17毫米，系统总长为4.23毫米，放大倍数为5.14倍，成像分辨率为0.24微米/像素，工作波长为0.4微米到0.7微米的可见光波长区域，设计波长为0.643微米、0.591微米、0.542微米、0.5微米、0.466微米，其中设计中心波长为0.542微米，上述参数满足光学显微镜成像和设备小型化的实现需要，满足数字病理扫描效率提升以及高质量显微成像的实现需要。
前述显微物镜1的主要性能参数之间具体可以满足如下关系：
数值孔径与工作介质折射率以及入射光最大锥角的半角之间的关系：
NA＝n*sinθ-----------------------------------------------式1
其中，NA表示数值孔径，n表示工作介质折射率，θ表示入射光最大锥角的半角。
入射光最大锥角的半角与入瞳直径以及有效焦距之间的关系：
tanθ＝EPD/(2*EFL)----------------------------------------式2
其中，θ表示入射光最大锥角的半角，EPD表示入瞳直径，EFL表示有效焦距。
成像分辨率与放大倍数以及视野范围之间得关系：
δ＝ρ 2/(Mag*U)--------------------------------------------式3
其中，δ表示成像分辨率，ρ表示图像传感器的像素大小，Mag表示放大倍数，U表示单位长度；本实例中ρ具体为1.12微米，U具体为1微米，Mag具体为5.14，因此，成像分辨率具体为0.24微米/像素。
上述显微物镜1的所有透镜的材料均可以采用低熔点和高低色散搭配的玻璃。上述的材质高低色散搭配，也即第一透镜502选用高色散材料玻璃且第二透镜505选用低色散材料玻璃，或者第一透镜502选用低色散材料玻璃且第二透镜505选用高色散材料玻璃，通过上述高低色散的材质组合搭配，使光学色散相互补偿，实现色差的消除以及成像质量的提升。在一个具体的应用示例中，第一透镜502和第二透镜505两者可以是SCHOTT公司的编号NLAF35材料(Vd＝-2.6444)搭配编号NSK16(Vd＝-0.0007)材料，或者HOYA公司的编号NBF2(Vd＝-0.9575)材料搭配编号MBACD15(Vd＝2.1589)材料，又或者成都光明公司的编号DLAF82L(Vd＝-2.0274)材料搭配HZK7(Vd＝-0.2680)材料等。
所述显微物镜1的一种实施例，如图7所示，具体为沿光轴方向从左向右分别设置的物面50、第一透镜502、第二透镜505以及像面507。其中，物面50位于最左侧有限远，像面507位于最右侧有限远，第一透镜502的前表面以及第二透镜505的后表面均镀有半透头半反的光学介质分光薄膜。该半透半反的光学介质分光薄膜，具体为：一种半透半反光学介质分光镀膜，利用其光学性能，实现对入射到镀膜表面的光，一部分进行透射，一部分进行反射。
本发明显微物镜1的一种实施例，如图7所示，光在系统中的传播路径具体如下：首先沿光轴方向，从被 观测物体来的光照射到镀有第一半透半反光学介质分光薄膜501的第一透镜502前表面，第一透镜502前表面面向物面50为凹面，面向像面507为凸面，第一半透半反光学介质分光薄膜501的曲率与第一透镜502前表面的曲率相同，入射光被第一透镜502前表面镀膜反射的光不作成像，另一部分被透过的光通过第一透镜502及其后表面，照射到第二透镜505的前表面，第一透镜502的后表面面向物面50为凹面，面向像面507为凸面，第二透镜505的前表面面向物面50为凹面，面向像面507为凸面；光线通过第二透镜505的前表面，照射到镀有第二半透半反光学介质分光薄膜506的第二透镜505后表面，第二透镜505后表面面向物面50为凹面，面向像面507为凸面，第二透镜505后表面的光学镀膜的曲率与第二透镜505后表面的曲率相同；被第二透镜505后表面的第二半透半反光学介质分光薄膜506反射的光再次进入光学系统，透过第二透镜505后表面光学膜的光散射照射到像面507。
其中，再次进入光学系统的光，被第二透镜505所聚焦，再次进入第一透镜502，再通过第一透镜502前表面的第一半透半反光学介质分光薄膜501进行反射，最终聚焦照射到像面507上；因此像面507上具有散射的第一次光传播透射光，同时具有聚焦的折反射光，但是由于聚焦光的光照强度远大于散射光的光照强度，因此，像面507上能够成高信噪比的高清高质量的显微图像。
根据上述成像原理，在像面507上的光成分为发散的、没有形成焦点的完全透射光，以及汇聚的、形成成像焦点的多次反射光，多次反射光的辐照远远高于一次完全透射光，在成像中，完全透射光为噪声，多次反射光为成像，因此成像对比噪声的信噪比高，即使存在完全透射光，也对清晰成像不会造成较大影响。
前述的第一透镜502和第二透镜505可以均是圆形透镜。第一透镜502和第二透镜505之间具有间隔。间隔中可以充满空气或者液体，又或者间隔内设有其他透镜及其他透镜组合。第一透镜502的前表面和后表面的面型可以均为非球面，第二透镜505的前表面和后表面可以均为非球面。
本发明公开的显微物镜1光学系统的设计数据可以如表1所示。表1给出了上述的一种实施例：显微物镜1光学系统中每一片透镜表面以及半透半反光学介质分光薄膜的具体设计参数值。
表1为本发明的显微物镜光学系统的设计参数。
Index 透镜表面 曲率半径 厚度 材质
1 第一半透半反光学介质分光薄膜 -1.837 0  
2 第一透镜前表面 -1.837 0.55 NLAF35
3 第一透镜后表面 -1.282 0.849  
4 第二透镜前表面 -1.042 0.667 NSK16
5 第二透镜后表面 -2.321 0  
6 第二半透半反光学介质分光薄膜 -2.321 1.723  
图10显示了本实施例的显微物镜光学系统的调制传递函数MTF，接近衍射极限。图11显示了本实施例的光学系统的纵截面的光线特性，图12显示了本实施例的光学系统的横截面的光线特性。图13显示了本实施例的光学系统的纵截面的光程特性图，图14显示了本实施例的光学系统的横截面的光程特性图。图15显示了本实施例的光学系统点列图。图16显示了本实施例的光学系统视场场曲图，图17显示了本实施例的光学系统畸变图。这些性能图均表示了上述显微物镜光学系统具有良好的光学性能，成像质量接近完美成像，完全满足光学显微观察以及数字病理成像的要求。
进一步的，如图18所示，前述显微照明装置3的数量可以为多个、且依次排布形成显微照明装置阵列。如图19所示，显微物镜1的数量与显微照明装置3的数量相等、且一一对应，以形成物镜阵列。在该物镜阵列中，各第一透镜502依次排布形成第一透镜阵列，各第二透镜505依次排布形成第二透镜阵列。如图21和图22所示，前述数字图像传感器2的数量与显微物镜1的数量相等、且一一对应，以形成传感器阵列。
其中，第一透镜阵列与第二透镜阵列组成新型物镜阵列，能够对位置相近的多个组织区域进行同时的显微成像，有效实现高效的病理组织芯片观察与诊断、高速数字病理扫描。并且由多个显微照明装置3依次排布形成显微照明装置阵列，可以满足显微物镜1阵列的照明需求，且光照更加均匀。
如图18所示，本发明还可以包括连接板106，前述各显微照明装置3的光学腔102可以依次排布在连接板106上。具体来说，连接板106上可以依次间隔设有多个贯穿两端的通孔，其中，每个通孔为一个光学腔102。各米氏散射器件103一一对应地套设在相应的光学腔102内。在本示例中，通过设置的连接板106，方便固定各米氏散射器件103，使各米氏散射器件103形成一个整体。
进一步的，如图21和图22所示，前述的传感器阵列用于沿第一方向运动时，各数字图像传感器2所成的像在第二方向上依次无间隔排布；第一方向与第二方向垂直。其中，第一方向可以为图1和图2中的X方向，第二方向可以为图1和图2中的Y方向。
具体来说，因为各数字图像传感器2呈阵列排布，从而与数字图像传感器2一一对应的各显微物镜1也呈阵列排布。又因为各显微物镜1与数字图像传感器2一一对应地保持相对固定，从而传感器阵列运动时由显微物镜1所形成的物镜阵列会跟着同步运动。当传感器阵列和显微物镜1阵列一起沿第一方向运动时，比如沿图1和图2中X方向运动，显微物镜1阵列内的各显微物镜1同时对组织切片的各部分进行扫描，使各数字图像传感器2所形成的像在第二方向比如Y方向上依次无间隔排布。
在上述技术方案中，当显微物镜1阵列和数字图像传感器2阵列在单向对组织切片进行线性扫描时，可以并行拍摄并拼接显微图像，比现有技术中常规方法的速度提升了20倍以上，极大改善了数字病理扫描仪的用户使用体验，真正实现了数字病理的应用价值。
因为各显微物镜1与数字图像传感器2一一对应，从而由各显微物镜1所形成的阵列与传感器阵列两者的排布方式和方法是相一致的。下面具体以传感器阵列的排布方式和方法进行描述，本领域技术人员在得知传感器阵列的排布方式的基础上，可以推知显微物镜1阵列的排列方式。
其中，传感器阵列内的各数字图像传感器2可以具有多种不同的排布方式，比如可以呈倾斜的一字形排布，或者呈Z字形排布。
在传感器阵列内的各数字图像传感器2呈倾斜的一字型排布的示例中，如图21所示，传感器阵列沿第一方向可以具有N个平行间隔排布的行。N为大于或等于2的整数。其中，相邻的两行沿第一方向分别为第N1行和第N2行。N2＝N1+1，N1为大于或等于1的整数。第N2行沿第二方向相对第N1行偏移大小为FoV的距离。FoV为数字图像传感器2所成的像在第二方向上的尺寸大小。
在上述示例中，以N＝6具体举例说明。如图21所示，传感器阵列沿X方向依次具有第1行、第2行、第3行、第4行、第5行和第6行。其中，第2行相对第1行向Y方向偏移FoV的距离。第3行相对第2行向Y方向偏移FoV的距离。第4行相对第3行向Y方向偏移FoV的距离。第5行相对第4行向Y方向偏移FoV的距离。第6行相对第5行向Y方向偏移FoV的距离。
在传感器阵列内的各数字图像传感器2呈Z字形排布的示例中，如图22所示，传感器阵列沿第一方向具有N个平行间隔排布的行。N为大于或等于3的整数。传感器阵列中位于最外侧两行的数字图像传感器2的数量相等、且均为M1个。其它行的数字图像传感器2的数量为M2个，M1＝M2+1。其中，相邻的两行沿第一方向分别为第N1 行和第N2行。N2＝N1+1，N1为大于或等于1的整数。当N2小于N时，第N2行沿第二方向相对第N1行偏移大小为FoV的距离；当N2等于N时，第N2行沿第二方向相对第N1行凸出大小为FoV的距离；FoV为数字图像传感器2所成的像在第二方向上的尺寸大小。
在上述示例中，以N＝6具体举例说明。如图22所示，传感器阵列沿X方向依次具有第1行、第2行、第3行、第4行、第5行和第6行。第1行和第6行两者数字图像传感器2的数量相等，第2行至第5行四者数字图像传感器2的数量相等。第1行的数字图像传感器2的数量比第2行数字图像传感器2的数量多一个。其中，第2行相对第1行向Y方向偏移FoV的距离。第3行相对第2行向Y方向偏移FoV的距离。第4行相对第3行向Y方向偏移FoV的距离。第5行相对第4行向Y方向偏移FoV的距离。第6行相对第5行向Y方向凸出FoV的距离。
进一步的，如图21和图22所示，前述各行内数字图像传感器2的数量可以均为两个以上、且沿第二方向依次排布。各行内相邻两数字图像传感器2在第二方向上的距离相等、且均为r1。如此可以使传感器阵列的结构更加紧凑，体积较小。
在一个具体的应用示例中，前述传感器阵列的相应排布参数可以采用以下公式获得。其中，N为大于或等于(W+r)/FoV的最小整数。r1＝N*FoV-W。W为数字图像传感器2沿第二方向的尺寸大小；r为同一行内相邻两数字图像传感器2的加工工艺在第二方向上所能实现的最小间隔。
前述相邻两行在第一方向上的间隔为r2，r2为相邻两行内的数字图像传感器2的加工工艺在第一方向上所能实现的最小间隔。
通过上述公式所计算出的排布参数，可以使传感器阵列具有最小的排布结构，在扫描相同大小区域的组织切片时，采用上述方法排列的传感器阵列的体积较小，传感器阵列内各数字图像传感器2的有效利用率较高。
这里需要说明的是：前述FoV可以通过数字图像传感器2的图像测量获得。W可以通过测量数字图像传感器2的尺寸获得。r可以通过工艺评估获得。
下面以传感器阵列采用Z字形排布具体举例说明。
在第一实施例中，如图23所示，一种数字图像传感器2阵列，数字图像传感器2的尺寸如下：宽度W为5.18毫米，高度H为5.4毫米。成像范围FoV为1.0毫米。数字图像传感器2绑定与封装工艺规定，横向最小间距r为0.8毫米，纵向最小间距r2为0.82毫米。
因此，阵列的行数N计算如下：
(1)(W+r)/FoV＝(5.18+0.8)/1＝5.98。
(2)阵列的行数N取大于或等于5.98的最小整数，即阵列的行数N＝6。
(3)同一行内相邻两数字图像传感器2之间的间隔r1＝N*FoV-W＝6*1-5.18＝0.82。
其中，各行内数字图像传感器2的具体数量可以根据实际情况而定，具体在此不再赘述。
在第二实施例中，如图24所示，一种数字图像传感器2阵列，数字图像传感器2的尺寸如下：宽度W为8.5毫米，高度H为8.5毫米。成像范围FoV为1.0毫米。数字图像传感器2绑定与封装工艺规定，横向最小间距r为0.3毫米，纵向最小间距r2为0.3毫米。
因此，阵列的行数N计算如下：
(1)(W+r)/FoV＝(8.5+0.3)/1＝8.8
(2)阵列的行数N取大于或等于8.8的最小整数，即阵列的行数N＝9。
(3)同一行内相邻两数字图像传感器2之间的间隔r1＝N*FoV-W＝9*1-8.5＝0.5。
其中，各行内数字图像传感器2的具体数量可以根据实际情况而定，具体在此不再赘述。
进一步的，如图25和图26所示，本发明的数字化病理成像设备还包括固定板61，固定板61上设有安装孔 62。安装孔62的数量与显微物镜1的数量相等、且一一对应；各显微物镜1一一对应地安装在相应的安装孔62内，且第一透镜502位于安装孔62的一端，第二透镜505位于安装孔62的另一端。
具体来说，前述固定板61上的多个安装孔62呈与显微物镜1相同的阵列排布，各显微物镜1一一对应地安装在相应的安装孔62内后，可以实现对呈阵列排布的显微物镜1进行固定。
在上述提供的技术方案中，通过将多个传统的支架集成在一起，形成一体式具有阵列安装孔62的固定支架(即固定板61)，减小了传统支架的壁厚，实现了阵列式显微物镜1的集成化固定。
在一个具体的应用示例中，如图26所示，前述第一透镜502的外径小于第二透镜505的外径。安装孔62包括依次连接的第一孔段601、第二孔段602和第三孔段603。第一孔段601、第二孔段602和第三孔段603三者的外径依次减小。其中，第一透镜502固定在第一孔段601上，第二透镜505固定在第三孔段603上。在本示例中，第一孔段601和第三孔段603两者的长度较短，两者主要用于固定安装第一透镜502和第二透镜505。从第一透镜502出射的光可以穿过第二孔段602照射到第二透镜505上。
在上述示例中，通过加工与透镜的外径相一致的孔段，具有方便安装固定透镜的效果，节省了固定支架的体积，有利于固定支架的小型化。
进一步的，如图25和图26所示，前述第一孔段601的侧壁上可以设有第一缺口621，该第一缺口621内填充有光粘胶剂64。前述的第一透镜502通过光粘胶剂64固定在第一孔段601上。其中，为了保证第一透镜502的固定效果，优选的，第一缺口621的数量可以为两个以上，且绕第一孔段601呈圆形均匀分布。在一个具体的应用示例中，第一缺口621的数量为四个。
同样的，如图25和图26所示，前述第三孔段603的侧壁上可以设有第二缺口622，第二缺口622内填充有光粘胶剂64。前述的第二透镜505通过光粘胶剂64固定在第三孔段603上。其中，为了保证第二透镜505的固定效果，优选的，第二缺口622的数量可以为两个以上，且绕第三孔段603呈圆形均匀分布。在一个具体的应用示例中，第二缺口622的数量为四个。
进一步的，如图26所示，当第一孔段601的侧壁上设有第一缺口621、且第二孔段602的侧壁上设有第二缺口622时，上述的第一缺口621可以位于第一孔段601的靠近第二孔段602的一端，第二缺口622位于第三孔段603的背离第二孔段602的一端。在本示例中，通过将第一缺口621和第二缺口622设置在相应孔段的光出射侧，如此有利于提高固定支架光入射侧的美观。
进一步的，如图26所示，前述的第二孔段602可以呈锥台形，第二孔段602的中心线与第一透镜502或第二透镜505的中心线重合。因为从第一透镜502射出的光呈锥状发散地照射到第二透镜505上，而通过将第二孔段602的形状设置为与第一透镜502的光柱的形状一致，具有节省固定支架空间的效果，使第二孔段602的外径不至于太大而影响固定支架的结构强度。
进一步的，如图27所示，本发明的数字化病理成像设备还可以包括图像数据采集控制器7、数据总线接口8、随机存储器9、中央处理器10、非易失性存储器11和显示输出端口12。
其中，数字图像传感器2通过并行数据接口与图像数据采集控制器7相连，图像数据采集控制器7用于读取数字图像传感器2传输来的数字图像数据；图像数据采集控制器7与随机存储器9通过数据总线接口8进行连接，图像数据采集控制器7通过数据总线接口8向随机存储器9传送数字图像数据；中央处理器10与随机存储器9、非易失性存储器11以及显示输出端口12通过电路总线连接，中央处理器10用于读取随机存储器9中的数字图像数据，将数字图像数据存储入非易失性存储器11中，同时输出到显示输出端口12用于图像数据显示。
前述的数字图像传感器2可以为具有光电转换并生成数字信号的传感器。图像数据采集控制器7以及中央处理器10两者可以为具有串行计算及逻辑处理的处理器芯片或电子系统、或者具有并行计算及逻辑处理的处理器 芯片或电子系统。优选的，图像数据采集控制器7以及中央处理器10可以为现场可编程门阵列，或者中央处理单元。前述图像数据采集控制器7用于并行或者串行地接收图像采集装置的方法或者通信协议，以对图像数据采集处理。图像数据采集控制器7还采用串行或者并行数据计算的方法对图像数据进行预先处理。所述串行或者并行数据计算的方法可以为图像数据格式的转换计算方法，和/或图像数据压缩的计算方法，和/或图像色彩调整的计算方法。中央处理器10用于将随机存储器9中存储的数据进行读取，以直接存储器访问的方式将随机存储器9中读取的数据写入显示输出端口12。
前述的数据总线接口8可以为从图像数据采集控制器7到随机存储器9之间的数据总线及硬件接口。优选的，数据总线接口8为PCI-express总线及接口、或者USB总线及接口、或并行传输总线及接口。前述的随机存储器9可以为具有数据缓冲存取的寄存器。优选的，随机存储器9为预存缓冲器，或者双倍数据率随机存取存储器，又或者双倍数据率同步动态随机存取存储器。随机存储器9用于以直接存储器访问的方式将读取的总线接口数据写入。
前述的非易失性存储器11可以为电源关闭后，所存储的数据不会消失的计算机存储器。优选的，非易失性存储器11为只读存储器，或者磁盘存储器，又或者固体硬盘存储器。非易失性存储器11用于将随机存储器9中存储的数据进行读取，以直接存储器访问的方式将读取的随机存储器9数据写入。
本发明是一种面向计算机的大型图像数据采集、传输、显示、存储方法，具体是将多台数字相机或数字扫描仪等数字化图像采集设备传输来的数字图像大数据高速地上传到数字图像处理系统并实时显示与高速存储的方法，以解决传统的数据传输方法对数字图像大数据无法实现短时间的高速传输、显示缓慢的问题。
一种大型数字图像数据的高速传输方法，是一种针对数字图像大数据高速传输、显示与存储的新式数据高速传输技术。首先图像数据采集控制器7对数字图像传感器2进行数据读取，通过图像数据采集控制器7内集成的数据处理单元对图像数据进行色彩调整、数据格式变换以及数据压缩等预处理后，将数字图像大数据送入数据传输总线；其次在运行于中央处理器10上的控制程序切换中央处理器10与总线控制器对数据传输总线的控制权，将读取到数据传输总线的大数据，通过直接存储器访问的方式，写入随机存储器9中，最后控制程序将对数据传输总线的控制权由总线控制器交回中央处理器10中，通过数据传输总线以及直接存储器访问的方式，将随机存储器9中的数据直接写入数据显示端口，在图像数据显示的同时，后台自动将图像大数据以直接存储器访问的方式写入非易失性存储器11中，实现数字图像大数据的高速图像显示与非易失存储。
本发明中，数据传入随机存储器9时，没有经过中央处理器10，而是通过数据总线直接写入随机存储器9中，因此数据总线上的数据传输速度与随机存储器9的数据传输速度的最小值决定了本发明数据传输速度的最大值，当数据总线采用PCI Express 3.0 16通道接口时，最高传输速度为252Gbit/s，当随机存储器9采用DDR4 SDRAM PC4-34100时，最高传输速度为272.8Gbit/s，因此，此种情况下，本发明的最高传输速度为252Gbit/s，对于数据量约32Gbit的数字病理全切片图像的传输来说，最短传输时间约0.13秒，符合实时数据传输的需要。
本发明中，数据传入显示输出端口12时，中央处理器10直接读取随机存储器9中的数据，将其送入显示输出端口12，因此随机存储器9的数据传输速度与显示输出端口12数据传输速度的最小值，决定了本发明显示输出速度的最大值，当随机存储器9采用DDR4 SDRAM PC4-34100时，最高传输速度为272.8Gbit/s，当显示输出端口12采用HDMI2.1接口协议时，最高传输速度为48Gbit/s，因此，在此种情况下，本发明的最高显示输出速度为48Gbit/s，对于数据量约32Gbit的数字病理全切片图像的传输来说，最短传输时间约0.7秒，符合高速数据显示的需要。
本发明中，中央处理器10直接读取随机存储器9中的数据并送入显示输出端口12的同时，也通过数据总线将数据送入非易失性存储器11中，因此随机存储器9的数据传输速度与非易失性存储器11的数据传输速度的 最小值，决定了本发明数据储存速度的最大值，当随机存储器9采用DDR4 SDRAM PC4-34100时，最高传输速度为272.8Gbit/s，当非易失性存储器11的数据传输接口采用S-ATA 3.0协议时，最高传输速度为6Gbit/s，因此，在此种情况下，本发明的最高数据存储速度为6Gbit/s，对于数据量约32Gbit的数字病理全切片图像的存储来说，最短存储时间约5.3秒，由于数字图像输出显示后，使用者通常需要进行观察，特别是在数字病理诊断过程中，对于数字病理图像进行观察和诊断的时间至少需要20秒(一般病理诊断的最短时间)，因此本发明的数据存储时间符合高速数据存储的需要。
这里需要说明的是：在不冲突的情况下，本领域的技术人员可以根据实际情况将上述各示例中相关的技术特征相互组合，以达到相应的技术效果，具体对于各种组合情况在此不一一赘述。
以上所述仅是本发明的优选实施方式，本发明的保护范围并不仅局限于上述实施例，凡属于本发明思路下的技术方案均属于本发明的保护范围。应当指出，对于本技术领域的普通技术人员来说，在不脱离本发明原理前提下的若干改进和润饰，这些改进和润饰也应视为本发明的保护范围。

Claims (28)

  1. 一种数字化病理成像设备，其特征在于，包括显微物镜(1)、数字图像传感器(2)和显微照明装置(3)；
    所述显微照明装置(3)包括光源(101)、米氏散射器件(103)、光学腔(102)和聚光镜(105)；光源(101)位于米氏散射器件(103)的一侧，聚光镜(105)位于米氏散射器件(103)的另一侧，所述米氏散射器件(103)套设在光学腔(102)内；光源(101)用于发出光照射到米氏散射器件(103)上；米氏散射器件(103)用于将光源(101)射入的光发散照射到聚光镜(105)上；聚光镜(105)用于将米氏散射器件(103)射入的光聚焦输出到被测体上；
    所述显微物镜(1)包括沿光轴方向依次设置的第一透镜(502)和第二透镜(505)，所述显微物镜(1)通过第一透镜(502)接收从被测体射入的光；第一透镜(502)面向物面(50)的表面为前表面，面向像面(507)的表面为后表面；第二透镜(505)面向物面(50)的表面为前表面，面向像面(507)的表面为后表面；第一透镜(502)前表面镀有第一半透半反光学介质分光薄膜(501)，第二透镜(505)后表面镀有第二半透半反光学介质分光薄膜(506)；
    所述数字图像传感器(2)用于接收从第二透镜(505)射入的光，并进行数字成像。
  2. 根据权利要求1所述的数字化病理成像设备，其特征在于，
    所述显微照明装置(3)的数量为多个、且依次排布形成显微照明装置阵列；
    所述显微物镜(1)的数量与所述显微照明装置(3)的数量相等、且一一对应，以形成物镜阵列；
    所述数字图像传感器(2)的数量与所述显微物镜(1)的数量相等、且一一对应，以形成传感器阵列。
  3. 根据权利要求2所述的数字化病理成像设备，其特征在于，
    所述传感器阵列用于沿第一方向运动时，各数字图像传感器(2)所成的像在第二方向上依次无间隔排布；所述第一方向与第二方向垂直。
  4. 根据权利要求3所述的数字化病理成像设备，其特征在于，
    所述传感器阵列沿第一方向具有N个平行间隔排布的行，N为大于或等于2的整数；
    其中，相邻的两行沿第一方向分别为第N1行和第N2行，N2＝N1+1，N1为大于或等于1的整数；第N2行沿第二方向相对第N1行偏移大小为FoV的距离，FoV为数字图像传感器(2)所成的像在第二方向上的尺寸大小。
  5. 根据权利要求3所述的数字化病理成像设备，其特征在于，
    所述传感器阵列沿第一方向具有N个平行间隔排布的行，N为大于或等于3的整数；传感器阵列中位于最外侧两行的数字图像传感器(2)的数量相等、且均为M1个，其它行的数字图像传感器(2)的数量为M2个，M1＝M2+1；
    其中，相邻的两行沿第一方向分别为第N1行和第N2行，N2＝N1+1，N1为大于或等于1的整数；当N2小于N时，第N2行沿第二方向相对第N1行偏移大小为FoV的距离；当N2等于N时，第N2行沿第二方向相对第N1行凸出大小为FoV的距离；FoV为数字图像传感器(2)所成的像在第二方向上的尺寸大小。
  6. 根据权利要求4或5所述的数字化病理成像设备，其特征在于，
    各行内数字图像传感器(2)的数量均为两个以上、且沿第二方向依次排布；
    各行内相邻两数字图像传感器(2)在第二方向上的距离相等、且均为r1。
  7. 根据权利要求6所述的数字化病理成像设备，其特征在于，
    N为大于或等于(W+r)/FoV的最小整数；
    r1＝N*FoV-W；
    其中，W为数字传感器沿第二方向的尺寸大小；r为同一行内相邻两数字图像传感器(2)的加工工艺在第二方向上所能实现的最小间隔。
  8. 根据权利要求6所述的数字化病理成像设备，其特征在于，
    相邻两行在第一方向上的间隔为r2，r2为相邻两行内的数字图像传感器(2)的加工工艺在第一方向上所能实现的最小间隔。
  9. 根据权利要求2至5、7、8中任一项所述的数字化病理成像设备，其特征在于，还包括固定板(61)，所述固定板(61)上设有安装孔(62)；
    所述安装孔(62)的数量与显微物镜(1)的数量相等、且一一对应；各所述显微物镜(1)一一对应地安装在相应的安装孔(62)内，且第一透镜(502)位于安装孔(62)的一端，第二透镜(505)位于安装孔(62)的另一端。
  10. 根据权利要求9所述的数字化病理成像设备，其特征在于，
    所述第一透镜(502)的外径小于所述第二透镜(505)的外径；
    所述安装孔(62)包括依次连接的第一孔段(601)、第二孔段(602)和第三孔段(603)，所述第一孔段(601)、第二孔段(602)和第三孔段(603)三者的外径依次减小；
    其中，所述第一透镜(502)固定在所述第一孔段(601)上，所述第二透镜(505)固定在第三孔段(603)上。
  11. 根据权利要求10所述的数字化病理成像设备，其特征在于，
    所述第一孔段(601)的侧壁上设有第一缺口(621)，所述第一缺口(621)内填充有光粘胶剂(64)，所述第一透镜(502)通过所述光粘胶剂(64)固定在所述第一孔段(601)上；
    和/或，所述第三孔段(603)的侧壁上设有第二缺口(622)，所述第二缺口(622)内填充有光粘胶剂(64)，所述第二透镜(505)通过所述光粘胶剂(64)固定在所述第三孔段(603)上。
  12. 根据权利要求11所述的数字化病理成像设备，其特征在于，
    当第一孔段(601)的侧壁上设有第一缺口(621)、且第三孔段(603)的侧壁上设有第二缺口(622)时，所述第一缺口(621)位于第一孔段(601)的靠近第二孔段(602)的一端，所述第二缺口(622)位于所述第三孔段(603)的背离第二孔段(602)的一端。
  13. 根据权利要求10至12中任一项所述的数字化病理成像设备，其特征在于，
    所述第二孔段(602)呈锥台形，所述第二孔段(602)的中心线与第一透镜(502)或第二透镜(505)的中心线重合。
  14. 根据权利要求1至5、7、8、10至12中任一项所述的数字化病理成像设备，其特征在于，
    所述光源(101)为发光二极管，或者半导体激光器。
  15. 根据权利要求1至5、7、8、10至12中任一项所述的数字化病理成像设备，其特征在于，
    所述米氏散射器件(103)，是一种分布着米氏散射介质粒子(104)的固体光学器件，该光学器件为透明，或者半透明，光学器件的折射率小于米氏散射介质粒子(104)的折射率。
  16. 根据权利要求1至5、7、8、10至12中任一项所述的数字化病理成像设备，其特征在于，
    所述光学腔(102)，是包裹在米氏散射器件(103)外部的两端开口的中空筒状封闭腔，其内壁为反射光的镜面，或者黑色氧化层表面。
  17. 根据权利要求1至5、7、8、10至12中任一项所述的数字化病理成像设备，其特征在于，
    所述聚光镜(105)，是一种能够将均匀光传播方向进行收缩，进行聚光照射的光学透镜或者光学透镜组合。
  18. 根据权利要求1至5、7、8、10至12中任一项所述的数字化病理成像设备，其特征在于，
    所述光源(101)通过光学胶粘接固定在米氏散射器件(103)的一侧，聚光镜(105)通过光学胶粘接固定在米氏散射器件(103)的另一侧。
  19. 根据权利要求1至5、7、8、10至12中任一项所述的数字化病理成像设备，其特征在于，
    第一透镜(502)和第二透镜(505)是圆形透镜，第一透镜(502)和第二透镜(505)之间具有间隔；间隔中充满空气或者液体，又或者间隔内设有其他透镜及其他透镜组合。
  20. 根据权利要求1至5、7、8、10至12中任一项所述的数字化病理成像设备，其特征在于，
    第一透镜(502)的前表面和后表面的面型为非球面，第二透镜(505)的前表面和后表面为非球面。
  21. 根据权利要求1至5、7、8、10至12中任一项所述的数字化病理成像设备，其特征在于，还包括图像数据采集控制器(7)、数据总线接口(8)、随机存储器(9)、中央处理器(10)、非易失性存储器(11)和显示输出端口(12)；
    其中，数字图像传感器(2)通过并行数据接口与图像数据采集控制器(7)相连，图像数据采集控制器(7)用于读取数字图像传感器(2)传输来的数字图像数据；图像数据采集控制器(7)与随机存储器(9)通过数据总线接口(8)进行连接，图像数据采集控制器(7)通过数据总线接口(8)向随机存储器(9)传送数字图像数据；中央处理器(10)与随机存储器(9)、非易失性存储器(11)以及显示输出端口(12)通过电路总线连接，中央处理器(10)用于读取随机存储器(9)中的数字图像数据，将数字图像数据存储入非易失性存储器(11)中，同时输出到显示输出端口(12)用于图像数据显示。
  22. 根据权利要求21所述的数字化病理成像设备，其特征在于，
    图像数据采集控制器(7)以及中央处理器(10)为具有串行计算及逻辑处理的处理器芯片或电子系统、或者具有并行计算及逻辑处理的处理器芯片或电子系统、又或者兼具串行以及并行计算及逻辑处理的处理器芯片或电子系统。
  23. 根据权利要求21所述的数字化病理成像设备，其特征在于，
    数据总线接口(8)为从图像数据采集控制器(7)到随机存储器(9)之间的数据总线及硬件接口。
  24. 根据权利要求21所述的数字化病理成像设备，其特征在于，
    随机存储器(9)为具有数据缓冲存取的寄存器；和/或，非易失性存储器(11)为电源关闭后，所存储的数据不会消失的计算机存储器。
  25. 根据权利要求21所述的数字化病理成像设备，其特征在于，
    图像数据采集控制器(7)用于并行或者串行接收数字图像传感器(2)的方法或者通信协议，以对图像数据采集处理，并采用串行或者并行数据处理算法，对图像数据进行预先处理。
  26. 根据权利要求21所述的数字化病理成像设备，其特征在于，
    随机存储器(9)用于以直接存储器访问的方式将读取的总线接口数据写入。
  27. 根据权利要求21所述的数字化病理成像设备，其特征在于，
    中央处理器(10)用于将随机存储器(9)中存储的数据进行读取，以直接存储器访问的方式将随机存储器(9)中读取的数据写入显示输出端口(12)。
  28. 根据权利要求21所述的数字化病理成像设备，其特征在于，
    非易失性存储器(11)用于将随机存储器(9)中存储的数据进行读取，以直接存储器访问的方式将读取的随机存储器(9)数据写入。
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