CN110470668A - A kind of full visual field imaging device and method of histopathologic slide - Google Patents
A kind of full visual field imaging device and method of histopathologic slide Download PDFInfo
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- CN110470668A CN110470668A CN201910859462.1A CN201910859462A CN110470668A CN 110470668 A CN110470668 A CN 110470668A CN 201910859462 A CN201910859462 A CN 201910859462A CN 110470668 A CN110470668 A CN 110470668A
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- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N1/00—Sampling; Preparing specimens for investigation
- G01N1/28—Preparing specimens for investigation including physical details of (bio-)chemical methods covered elsewhere, e.g. G01N33/50, C12Q
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- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N1/00—Sampling; Preparing specimens for investigation
- G01N1/28—Preparing specimens for investigation including physical details of (bio-)chemical methods covered elsewhere, e.g. G01N33/50, C12Q
- G01N1/36—Embedding or analogous mounting of samples
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- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N21/00—Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
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Abstract
The invention discloses the full visual field imaging devices and method of a kind of histopathologic slide, the histopathologic slide observed will be needed directly to be prepared into image sensor chip photosensitive area surface, then nearly directional light illumination is provided right above image sensor chip, its projection information is directly recorded by image sensor chip again, finally the analysis of digital microscopy images in the full visual field is transferred on computer and is checked and supplied Pathologis diagnosis.With existing based on compared with optical microscopy histopathologic slide detection process, the present invention normal process that not only prepared by compatible existing histotomy, structure complexity is low, imaging process is easy, and it can be realized the imaging of full field range while guaranteeing resolution ratio, help to improve the detection efficiency of histopathologic slide's sample, the workload for greatly reducing clinical examination doctor, the accuracy for improving work efficiency and diagnosing.
Description
Technical field
The present invention relates to optical microscopy imaging technical field, the full visual field imaging device of specifically a kind of histopathologic slide
And method.
Background technique
Pathologic finding has been widely used in clinical position and scientific research.Corpse pathologic finding is substantially carried out in clinicing aspect
With surgery Pathology inspection.The purpose of surgery Pathology inspection, one is to clarify a diagnosis and verify preoperative diagnosis, improves clinical examine
It cuts off the water supply flat；After two are that diagnosis is clear, the therapeutic scheme and estimating prognosis of next step can be determined, and then improve clinical treatment water
It is flat.By Clinical and Pathological Analysis, it also can get a large amount of extremely valuable scientific research datas.
Pathological section is one kind of Pathologic specimen.The tissue or internal organs that partially have lesion are passed through into various chemistry when production
The processing of product and burying storage is allowed to fixed hardening, thinly slices, be adhered on slide on slicer, and dye is supplied with various colors
It checks under the microscope, observes pathological change, make pathological diagnosis, provide help for clinical diagnosis and treatment.
Histopathologic slide is mainly based upon in the total diagnostic method of hospital pathology department and carries out under an optical microscope at present
Observation, optical microscopy cause field range to strongly reduce with the increase of amplification factor due to the presence of lens system, therefore absolutely
The field number of optical microscopy is in millimeter or submillimeter magnitude under most of scene, and which results in optical microscopies can not
The one-time imaging to histotomy is completed, and in order to observe and compare different zones, medical staff just has to repeatedly constantly
Ground moves the visual field, while proposing high requirement to the working experience richness of diagnosis medical staff, also results in pathology department and examines
The scarcity of resources of disconnected doctor.The method of another automation collection data is exactly to install high-precision machinery additional under the microscope to sweep
Imaging apparatus is spelled by the micro-image of hundreds and thousands of obtained after mechanical scanning single low coverages using software algorithm
It is bonded into the pathological section micro-image in a full visual field, not only high-precision hardware cost increases severely, is time-consuming this method, but also
Due to different production slice proficiency's difference cause be sliced out-of-flatness, the variation in clear face so that bring microscope is focused,
Further result in the full field-of-view image inaccuracy or empty burnt of splicing.At the same time, the splicing carried out by algorithm is in low coverage
Between stitching portion be easy to appear deformity and image information distortion.
Therefore, seek that a kind of structure is simple, operation is brief, and can be realized under full field range histopathologic slide at
The detection method of picture is just particularly important.
Summary of the invention
It is an object of the invention to be directed to the defect of existing histopathologic slide's detection method and device, propose that one kind is based on
The full visual field imaging device of the histopathologic slide of projection theory and method, structure is simple, and operation is brief, and its field range is only
Depending on the size of image sensor chip photosensitive area, can to centimetre and inferior centimeter order size under histopathologic slide it is disposable
Full visual field imaging, so that the doctor of clinical disease natural sciences diagosis is not necessarily to stare at the mobile visual field under microscope to check.
In order to achieve the above objectives, The technical solution adopted by the invention is as follows:
A kind of full visual field imaging device of histopathologic slide includes light source module, sample carrying and image-forming module, drive
Dynamic control module and computer；
Sample carrying and image-forming module include image sensor chip, histopathologic slide's sample, resinene,
In, described image sensor chip is used for for directly recording the projection information of histopathologic slide's sample, the resinene
Histopathologic slide's sample is locked in the photosensitive area surface of image sensor chip；
The light source module is placed in the surface of image sensor chip, and the light-emitting surface covering of the light source module is whole
The photosensitive area of a image sensor chip, the light source module is for providing illumination when being imaged；
The drive control module for driving image sensor chip and light source module to work normally, and respectively with light source
Module, image sensor chip and computer connection；
The computer is for receiving and handling the collected histopathologic slide's sample projection of image sensor chip institute
Micro-image data are simultaneously shown.
Further, the light source module uses redgreenblue LED light source or white LED light source, redgreenblue LED
Vertical range Z >=5cm between the photosensitive area of light source or white LED light source and image sensor chip.
Further, redgreenblue LED light source and monochromatic image sensor chip corresponding matching, alternatively, white light LEDs
The color image sensor chip corresponding matching of light source and integrated optical filter.
Further, described image sensor chip uses cmos image sensor array, half floating transistor array, answers
Close Dielectric photosensitive detector array, double device photodetector cell arrays based on composite dielectric gate or division gate type MOSFET
One of imaging detector arrays, size≤1 μm of 1 μ m of single pixel unit, and the pixel scale of imaging sensor
≥10000×10000。
Half floating transistor, for example, it may be document (Wang P, Lin X, Liu L, et al.A semi-
floating gate transistor for low-voltage ultrafast memory and sensing
Operation. [J] .Science (NewYork, N.Y.), 2013,341 (6146): 640-643.) half floating transistor
Structure is also possible to half floating gate transistor structures described in Chinese patent CN201410201614.6, including semiconductor substrate (P
Type)；N+ type source electrode is formed by ion implanting in semiconductor substrate, forms big N-type drain by two step ion implantings；Partly lead
Underlying dielectric is successively arranged above body substrate, half floating gate, top layer medium, control gate, underlying dielectric centre forms one by etching
A slot, so that half floating gate is directly contacted with drain electrode.The erasable operation for comparing traditional floating transistor is to pass through applying high voltage
Insulating medium layer is crossed to control electron tunneling, half floating transistor uses the quantum tunneling effect of TFET in silicon body and adopts
Traditional erasable window of silica data is substituted with PN junction diode.
The composite dielectric gate light-sensitive detector, for example, it may be light described in Chinese patent CN200910024504.6
Quick composite dielectric gate MOSFET (Metal-Oxide-Semiconductor Field Effect Transistor) detector.The light-sensitive detector includes: semiconductor substrate (p-type)；Right above semiconductor substrate according to
It is secondary to be equipped with bottom dielectric, photoelectron accumulation layer, top layer dielectric, control gate；(close to laminated medium in semiconductor substrate
Two sides) pass through ion implantation doping formation N-type source and drain electrode.By adding the grid for being greater than threshold voltage in control grid
Voltage, voltage difference is 0 between source electrode and drain electrode, and P type substrate and source are arranged a big voltage difference and generate on substrate relatively
Wide depletion region, the cold electronics generated in such substrate accelerate to obtain under the action of electric field in depletion region towards grid direction
Energy, electronics is directed across this potential barrier and enters bottom Jie when this energy is greater than the potential barrier between substrate and underlying dielectric
Matter, and moved with very high speed towards grid direction under the action of underlying dielectric electric field, generate the Injection Current of grid.
Double device photodetector units based on composite dielectric gate, for example, it may be Chinese patent
Double device photodetector units described in CN201610592997.3 based on composite dielectric gate.The photodetector unit includes tool
The part composite dielectric gate MOS-C and the compound medium grid MOSFET part with reading informational function for having sensitization function, and this
Two parts are formed in the top of same P-type semiconductor substrate；The composite dielectric gate MOS-C is partly comprised in P-type semiconductor lining
The Charged Couple layer set, the first top layer dielectric layer and the first control grid are successively folded above bottom, wherein in P-type semiconductor substrate
In and Charged Couple layer lower section be equipped with N-type implanted layer；The compound medium grid MOSFET is partly comprised in the P-type semiconductor
The underlying dielectric layer set, the Charged Couple layer, the second top layer dielectric layer and the second control grid are successively folded above substrate,
In, the side in the P-type semiconductor substrate and close to underlying dielectric layer is equipped with N-type source region and N-type drain electrode, described
In the P-type semiconductor substrate and lower section of underlying dielectric layer is equipped with threshold value and adjusts injection region；In the P-type semiconductor substrate, N-type note
Enter and is separated between layer and N-type source region, N-type drain electrode by setting shallow trench isolation region and P+ type injection region.When work: control gate
Pole adds 0 bias, and substrate adds back bias voltage pulse, forms depletion layer in the substrate, when light is incident in depletion layer photon by semiconductor
When absorption, photoelectron is generated, photoelectron is moved to substrate and grid oxygen interface in driving for grid voltage, poly- in the interface
Collection characterizes photoelectron number with this, optical signal is converted to quantifiable telecommunications so that reading transistor threshold voltage variation
Number.
The division gate type MOSFET imaging detector, for example, it may be described in Chinese patent CN201210349285.0
Division gate type MOSFET imaging detector.The structure of the imaging detector includes: to divide right above substrate p-type semiconductor material
Not She You two layers insulating dielectric materials and control grid, be equipped with photoelectron accumulation layer between two layers of insulating dielectric materials.Control gate
It is the window transparent or semitransparent to the light in detector detection wave-length coverage at pole-face or substrate layer at least one.Substrate p-type
The two sides of floating-gate MOS FET are equipped with selection gate above semiconductor material, and insulating medium layer is equipped between selection gate and substrate,
Dielectric layer material and thickness are identical as bottom insulating medium layer.The peripheral p-type for the substrate that two selection gates are controlled serves as a contrast
Bottom is equipped with N-type semiconductor area, constitutes the source electrode and drain electrode of splitting bar MOSFET.Two selection gates are located at floating-gate MOS FET's
Two sides, and separated between selection gate and control grid and photoelectron accumulation layer with insulating dielectric materials, and grid institute will be controlled
The substrate of control and the source electrode and drain electrode of imaging detector separate.Second layer insulating medium layer with control gate contact is to prevent
Material of the charge loss stored in photoelectron accumulation layer to control grid, the first layer contacted with substrate p-type semiconductor material
Insulating medium layer, that is, underlying dielectric, the substrate channel and photoelectron accumulation layer being effectively isolated under control grid control, in grid electricity
When pressing sufficiently high or incident photon energy higher, the electronics in the channel is swept into photoelectron accumulation layer.Add in control grid
Positive bias pulse adds back bias voltage pulse on P-type semiconductor substrate, while adding a back bias voltage arteries and veins in two selection gates
Punching forms a depletion layer in the P-type semiconductor substrate under control grid control in this way, when light is incident on photon in depletion layer
When by semiconductor absorber, photoelectron will be generated, photoelectron is moved to channel and bottom insulating layer in driving for grid voltage
Interface.Since two selection gates are applied with a back bias voltage, thus in the P-type semiconductor substrate of selection gate control
In form a high electronic barrier, this high electronic barrier by control grid control under substrate have with N-type source and drain electrode
Effect keep apart, ensure that the photoelectron collected in substrate depletion layer will not be lost to source electrode and drain electrode direction, at the same source electrode with
Electronics in drain electrode must not also be entered in substrate depletion layer by the obstruction of this high potential barrier.It is sufficient when controlling positive bias added by grid
When enough big, the photoelectron collected in substrate depletion layer will enter photoelectron accumulation layer by way of F-N tunnelling；If incident light
Sub- energy is sufficiently high, and greater than the forbidden bandwidth of semiconductor and bottom insulating medium layer, photoelectron will can pass through direct tunnelling
Mode enters photoelectron accumulation layer.Photoelectricity sub-stage is being collected, source electrode and drain electrode can suitably apply sizeable positive bias,
Or direct floating.
Further, the thickness of histopathologic slide's sample is between 1 μm~5 μm, and the histopathologic slide
Sample directly prepares and is tightly attached to the photosensitive area surface of described image sensor chip.
The method by histopathologic slide's preparation on image sensor chip photosensitive area surface based on above-mentioned apparatus, including
Following steps:
(1) chip cleans: using the surface of deionized water and washes of absolute alcohol image sensor chip respectively, removes its table
Face impurity, is placed in drying in oven；
(2) it is sliced: the wax stone for being embedded with pathological tissue prepared being fixed on slicer, 1 μm~5 μ m-thicks are cut into
Thin slice, and thin slice is placed in pathological tissue drift baking instrument and is shakeout；
(3) chip fishes out piece: the fold to histopathologic slide shakeouts completely, carries out fishing piece with image sensor chip, really
Protect that histopathologic slide is smooth is attached on the photosensitive area of image sensor chip；
(4) chip is dried: the image sensor chip for being glued with histopathologic slide is placed in drying in oven；
(5) image sensor chip for being attached with histopathologic slide after drying dewaxing and dyeing: is sequentially placed into two
Toluene I, dimethylbenzene II each 10~20 minute, then be sequentially placed into the ethanol solution of descending concentrations each 4~6 minutes, then set again
In impregnating 4~6 minutes in distilled water, then conventional hematoxylin-eosin (HE) decoration method is selected to be dyed；
(6) dehydration with it is transparent: the image sensor chip for being attached with histopathologic slide after dyeing is sequentially placed into dense
Each 1~3 minute is spent in the ethanol solution to successively decrease, dehydration in baking oven is subsequently placed at, then handles through dimethylbenzene III to pathological tissue
It is sliced transparent；
(7) chip sealing: resinene is uniformly dripped in the imaging sensor for the histopathologic slide for being attached with transparence
On chip, sealing histopathologic slide.
Preferably, step (1) and (4) are placed in 50 DEG C~70 DEG C drying in baking oven.
The method of the full visual field imaging of histopathologic slide based on above-mentioned apparatus, includes the following steps:
S1., histopathologic slide is prepared into the surface of the photosensitive area of image sensor chip；
S2. it by image sensor chip access system, turns on the power switch, drive control module starts to work and drives figure
Projection micro-image data acquisition as sensor chip according to the time for exposure completion of setting to histopathologic slide, then will adopt
The data collected are transferred to computer；
S3. after computer is completed by image procossing and transmission module to the processing of micro-image data, data are transmitted
It is shown as image on to the display connecting with computer, and can be contracted by the mouse being connect with computer to the image
It puts and pulls to be checked.
Computer includes following concrete mode to the processing of micro-image data by image procossing and transmission module:
(1) the three width gray level images that redgreenblue LED light source and monochromatic image sensor chip corresponding matching obtain
IR、IG、IBIt denoises respectively, image enhancement processing, then one width color image I of final synthesisColor；Specific synthetic method is as follows:
IColor=IR×m1+IG×m2+IB×m3
Wherein, Coefficient m1、m2And m3For adjusting gray scale micro-image under three kinds of colour light sources of RGB in post synthesis
Photo chromic microimage IColorIn the weight occupied, 0 < m1≤ 1,0 < m2≤ 1,0 < m3≤1.By adjusting these three parameters, to calibrate
The color difference of the color image of synthesis makes result close to authentic sample color regime.
(2) colour that the color image sensor chip corresponding matching of white LED light source and integrated optical filter obtains
Image successively carries out denoising and image enhancement processing, directly obtains color image.
The present invention will need the histopathologic slide observed directly to be prepared into image sensor chip photosensitive area surface, then
Nearly directional light illumination is provided right above image sensor chip, then directly records its projection letter by image sensor chip
Breath, then by Digital Image Transmission to computer (PC).Optical microscopy histopathologic slide detection process phase is based on existing
Not only it is compatible with that the normal process of existing histotomy preparation, structure complexity is low, imaging process is easy than, the present invention, and
The imaging that can be realized full field range while guaranteeing resolution ratio, helps to improve the detection efficiency of histopathologic slide.
Detailed description of the invention
The full visual field imaging device general structure schematic diagram of Fig. 1 embodiment of the present invention histopathologic slide；
Tricolor LED light source structure schematic diagram used in Fig. 2 embodiment of the present invention；
Fig. 3 embodiment of the present invention shows the effect on the photosensitive area surface that histopathologic slide is prepared into image sensor chip
It is intended to, wherein (a) schematic three dimensional views, (b) side view；
Histopathologic slide is prepared into the method stream on the photosensitive area surface of image sensor chip by Fig. 4 embodiment of the present invention
Cheng Tu；
Forming monochrome image result and its partial enlarged view of Fig. 5 embodiment of the present invention to mouse intestinal histotomy；
Fig. 6 image sensor chip detector array schematic diagram；
Fig. 7 CMOS image sensor structure schematic diagram；
Half floating gate transistor structures schematic diagram of Fig. 8；
Fig. 9 composite dielectric gate light-sensitive detector structural schematic diagram；
Double device photodetector cellular construction schematic diagrams one of the Figure 10 based on composite dielectric gate；
Double device photodetector cellular construction schematic diagrams two of the Figure 11 based on composite dielectric gate；
Double device photodetector cellular construction schematic diagrams three of the Figure 12 based on composite dielectric gate；
Double device photodetector cellular construction schematic diagrams four of the Figure 13 based on composite dielectric gate；
Figure 14 divides gate type MOSFET imaging detector structural schematic diagram；
Fig. 1-14 mark meaning is as follows: 1- three-color LED light source, 2- image sensor chip, 3- photosensitive area, 4- pathological tissue
Section sample, 5- drive control module, 6- computer, 7- resinene.
Specific embodiment
Specific embodiments of the present invention will now be described in detail with reference to the accompanying drawings.
A kind of full visual field imaging device of histopathologic slide, as shown in Figure 1, include light source module, sample carrying with
Image-forming module, drive control module 5 and computer 6；
The sample carrying and image-forming module include image sensor chip 2, histopathologic slide's sample 4, resinene
7, wherein described image sensor chip 2 is for directly recording the projection information of histopathologic slide's sample, the resinene
7 for histopathologic slide's sample 4 to be locked in the photosensitive area surface of image sensor chip 2；
The structure of 2 detector array of described image sensor chip as shown in fig. 6, the detector array by a large amount of identical
Single pixel composition, the structure of the single pixel can be cmos image sensor array as shown in Figure 7, such as Fig. 8 institute
Half floating transistor shown is also possible to composite dielectric gate light-sensitive detector as shown in Figure 9, be also possible to as Figure 10, Figure 11,
Double device photodetector units shown in Figure 12, Figure 13 based on composite dielectric gate, can also be splitting bar as shown in figure 14
Type MOSFET imaging detector.The detector array that the image sensor chip 2 of the present embodiment uses is classified as base as shown in Figure 10
In double device photodetector cell arrays of composite dielectric gate, the size of the single pixel of described image sensor chip 2 is equal to
The pixel scale of 0.5 0.5 μm of μ m, imaging sensor is equal to 23000 × 23000, to guarantee full visual field when micro-imaging
With high-resolution and deposit.
The thickness of histopathologic slide's sample 4 is equal to 3 μm, and directly prepares the photosensitive area 3 in image sensor chip 2
On, preparation flow is as shown in Figure 4；Resinene 7 is used to histopathologic slide's sample 4 being locked in image sensor chip 2
The surface of photosensitive area 3 prevents rotting for histotomy, is conducive to save for a long time.
The light source module is placed in the surface of image sensor chip 2, and the light-emitting surface covering of the light source module
The photosensitive area 3 of whole image sensor chip 2, the light source module is for providing illumination when being imaged；
Three-color LED light source 1 or white LED light source can be selected in the light source module, wherein three-color LED light source 1 with do not collect
It is used at the monochrome image sensor chip corresponding matching of optical filter, and the cromogram of white LED light source and integrated optical filter
As sensor chip corresponding matching uses；As shown in Figure 2,1 structural representation of three-color LED light source used in the embodiment of the present invention
Figure, which contains red 1-1, green 1-2, tri- lamp beads of blue 1-3 respectively, and this three lamp beads can be controlled successively and be lighted；This three
Vertical range Z between color LED light source 1 and the photosensitive area 3 of image sensor chip 2 is equal to 10cm.
The drive control module 5 is used to drive the normal work of image sensor chip 2 and three-color LED light source 1, and divides
It is not connect with three-color LED light source 1, image sensor chip 2 and computer 6；The drive control module 5 can be added with FPGA
The mode of peripheral PCB circuit board is realized；
The computer 6 is thrown for receiving and handling the 2 collected histopathologic slide's sample 4 of institute of image sensor chip
Shadow micro-image data are simultaneously shown.
Histotomy is prepared to the present embodiment the operating method on 3 surface of photosensitive area of image sensor chip 2 below
Following specific descriptions are done, are included the following steps:
(1) chip cleans: using the surface of deionized water and washes of absolute alcohol image sensor chip 2 respectively, removes it
Surface impurity is placed in 60 DEG C of drying in baking oven；
(2) it is sliced: the wax stone for being embedded with pathological tissue prepared being fixed on slicer, the thin slice of 3 μ m-thicks is cut into,
And thin slice is placed in pathological tissue drift baking instrument and is shakeout；
(3) chip fishes out piece: the fold to histopathologic slide shakeouts completely, carries out fishing piece with image sensor chip 2, fishing
Piece process need to be operated slowly, it is ensured that on the smooth photosensitive area 3 for being attached to image sensor chip 2 of histopathologic slide；
(4) chip is dried: the image sensor chip 2 for being glued with histopathologic slide is placed in 60 DEG C of drying in baking oven；
(5) image sensor chip 2 for being attached with histopathologic slide after drying dewaxing and dyeing: is sequentially placed into two
Toluene I, dimethylbenzene II each 20 minute, then to be sequentially placed into dehydrated alcohol I, dehydrated alcohol II, 95% ethanol solution, 85% ethyl alcohol molten
Each 5 minutes in liquid and 75% ethanol solution, then be placed in distilled water and impregnate 5 minutes again, then select conventional hematoxylin-she
Red (HE) decoration method is dyed；
Dyeing course is as follows: image sensor chip 2 is placed in haematoxylin liquid 5 minutes first, takes out washing 2 minutes,
It is then handled with 0.5% hydrochloride alcohol color separation 8 seconds, then the washing oil blackeite carried out 20 minutes, is finally placed in the solution of Yihong and redyes 5
Minute；
(6) dehydration with it is transparent: the image sensor chip 2 for being attached with histopathologic slide after dyeing is sequentially placed into
Each 1 minute in 75% ethanol solution, 85% ethanol solution, 95% ethanol solution and dehydrated alcohol II, it is subsequently placed in baking oven and takes off
Water, then handled through dimethylbenzene III transparent to histopathologic slide；
(7) chip sealing: resinene 7 is uniformly dripped in the imaging sensor for the histopathologic slide for being attached with transparence
On chip 2, sealing histopathologic slide.
Through above-mentioned steps, histotomy prepares the effect on 3 surface of photosensitive area of image sensor chip 2, such as Fig. 3
(a), shown in (b).
Further, the operating procedure of the present embodiment in actual use is done described below, is included the following steps:
S1., histopathologic slide is prepared into the surface of the photosensitive area 3 of image sensor chip 2 according to the above method；
S1. it by 2 access system of image sensor chip, turns on the power switch, drive control module 5 is started to work and driven
Image sensor chip 2 is completed to adopt three kinds of color of light according to the projection information of lower histopathologic slide according to the time for exposure of setting
Collection, then collected data are transferred to computer 6；
(2) S3. computer 6 will be red green with transmission module (built-in computer normal image processing software) by image procossing
The three width gray level images that blue three-color LED light source and monochromatic image sensor chip corresponding matching obtain denoise respectively, image
After enhancing processing, then one width color image of final synthesis, then transfers data on the display being connect with calculator and show
At image, and the image can be zoomed in and out and be pulled by the mouse being connect with calculator to check.
The embodiment of the present invention puts imaging results schematic diagram monochromatic under mouse intestinal histotomy green LED light source and part
Big figure, as shown in Figure 5；Finally, completing colored synthesis processing by image procossing and transmission module, and show.
Above-described embodiment is only more excellent embodiment of the invention, is implemented according to the technical essence of the invention to above
Any simple modification, modification and the alternate variation that example is made, belong in the range of technical solution of the present invention.
Claims (9)
1. a kind of full visual field imaging device of histopathologic slide, which is characterized in that include light source module, sample carrying at
As module, drive control module and computer；
The sample carrying and image-forming module include image sensor chip, histopathologic slide's sample, resinene, wherein
For described image sensor chip for directly recording the projection information of histopathologic slide's sample, the resinene is used for will be sick
Reason tissue section sample is locked in the photosensitive area surface of image sensor chip；
The light source module is placed in the surface of image sensor chip, and the entire figure of light-emitting surface covering of the light source module
As the photosensitive area of sensor chip, the light source module is for providing illumination when being imaged；
The drive control module for driving image sensor chip and light source module to work normally, and respectively with light source die
Block, image sensor chip and computer connection；
The computer is micro- for receiving and handling the collected histopathologic slide's sample projection of image sensor chip institute
Image data is simultaneously shown.
2. a kind of full visual field imaging device of histopathologic slide according to claim 1, which is characterized in that the light source
Module uses redgreenblue LED light source or white LED light source, and redgreenblue LED light source or white LED light source and image pass
Vertical range Z >=5cm between the photosensitive area of sensor chip.
3. a kind of full visual field imaging device of histopathologic slide according to claim 2, which is characterized in that RGB three
Color LED light source and monochromatic image sensor chip corresponding matching, alternatively, the coloured silk of white LED light source and integrated optical filter
Color image sensor chip corresponding matching.
4. a kind of full visual field imaging device of histopathologic slide according to claim 1, which is characterized in that described image
Sensor chip uses cmos image sensor array, half floating transistor array, composite dielectric gate photosensitive detector array, base
It is single in one of double device photodetector cell arrays of composite dielectric gate or division gate type MOSFET imaging detector arrays
The size of a pixel unit≤1 μm of 1 μ m, and pixel scale >=10000 × 10000 of imaging sensor.
5. a kind of full visual field imaging device of histopathologic slide according to claim 1, which is characterized in that the pathology
The thickness of tissue section sample is between 1 μm~5 μm, and histopathologic slide's sample directly prepares and is tightly attached to the figure
As the photosensitive area surface of sensor chip.
6. one kind is prepared histopathologic slide in image sensor chip based on Claims 1 to 5 any one described device
The method on photosensitive area surface, which comprises the steps of:
(1) chip cleans: using the surface of deionized water and washes of absolute alcohol image sensor chip respectively, it is miscellaneous to remove its surface
Matter is placed in drying in oven；
(2) it is sliced: the wax stone for being embedded with pathological tissue prepared being fixed on slicer, the thin of 1 μm~5 μ m-thicks is cut into
Piece, and thin slice is placed in pathological tissue drift baking instrument and is shakeout；
(3) chip fishes out piece: the fold to histopathologic slide shakeouts completely, carries out fishing piece with image sensor chip, it is ensured that disease
Histotomy is smooth is attached on the photosensitive area of image sensor chip for reason；
(4) chip is dried: the image sensor chip for being glued with histopathologic slide is placed in drying in oven；
(5) image sensor chip for being attached with histopathologic slide after drying dewaxing and dyeing: is sequentially placed into dimethylbenzene
I, dimethylbenzene II each 10~20 minute, then be sequentially placed into the ethanol solution of descending concentrations each 4~6 minutes, then it is placed in steaming again
It is impregnated 4~6 minutes in distilled water, then conventional hematoxylin-eosin (HE) decoration method is selected to be dyed；
(6) dehydration with it is transparent: the image sensor chip for being attached with histopathologic slide after dyeing is sequentially placed into concentration and is passed
Each 1~3 minute in the ethanol solution subtracted, it is subsequently placed at dehydration in baking oven, then is handled through dimethylbenzene III to histopathologic slide
It is transparent；
(7) chip sealing: resinene is uniformly dripped in the image sensor chip for the histopathologic slide for being attached with transparence
On, sealing histopathologic slide.
7. it is according to claim 6 it is a kind of by histopathologic slide preparation image sensor chip photosensitive area surface side
Method, which is characterized in that step (1) and (4) are placed in 50 DEG C~70 DEG C drying in baking oven.
8. the method that a kind of full visual field of histopathologic slide based on Claims 1 to 5 any one described device is imaged,
It is characterized in that, includes the following steps:
S1., histopathologic slide is prepared into the surface of the photosensitive area of image sensor chip；
S2. it by image sensor chip access system, turns on the power switch, drive control module starts to work and image is driven to pass
Sensor chip is completed to acquire the projection micro-image data of histopathologic slide according to the time for exposure of setting, then will collect
Data be transferred to computer；
S3. after computer is completed by image procossing and transmission module to the processing of micro-image data, transfer data to
Computer connection display on be shown as image, and the image can be zoomed in and out by the mouse being connect with computer and
It pulls to be checked.
9. a kind of method of the full visual field imaging of tissue pathological slice according to claim 8, which is characterized in that S1. is used
Histopathologic slide is prepared into the surface of the photosensitive area of image sensor chip by claim 6 the method.
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| CN201910859462.1A CN110470668A (en) | 2019-09-11 | 2019-09-11 | A kind of full visual field imaging device and method of histopathologic slide |
| CN202020780265.9U CN212432993U (en) | 2019-09-11 | 2020-05-12 | Pathological tissue section's full field of vision image device |
| CN202010398702.5A CN111610187A (en) | 2019-09-11 | 2020-05-12 | Pathological tissue section's full field of vision image device |
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| CN113643981A (en) * | 2021-07-29 | 2021-11-12 | 上海华力集成电路制造有限公司 | Method for manufacturing semi-floating gate transistor with bimetallic control gate |
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| CN113643981A (en) * | 2021-07-29 | 2021-11-12 | 上海华力集成电路制造有限公司 | Method for manufacturing semi-floating gate transistor with bimetallic control gate |
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