CN105590079B - A kind of method and apparatus of multiple continuous automatically identifying and readings of biochip transmission signal - Google Patents
A kind of method and apparatus of multiple continuous automatically identifying and readings of biochip transmission signal Download PDFInfo
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- CN105590079B CN105590079B CN201510979230.1A CN201510979230A CN105590079B CN 105590079 B CN105590079 B CN 105590079B CN 201510979230 A CN201510979230 A CN 201510979230A CN 105590079 B CN105590079 B CN 105590079B
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- G06K—GRAPHICAL DATA READING; PRESENTATION OF DATA; RECORD CARRIERS; HANDLING RECORD CARRIERS
- G06K7/00—Methods or arrangements for sensing record carriers, e.g. for reading patterns
- G06K7/10—Methods or arrangements for sensing record carriers, e.g. for reading patterns by electromagnetic radiation, e.g. optical sensing; by corpuscular radiation
- G06K7/10544—Methods or arrangements for sensing record carriers, e.g. for reading patterns by electromagnetic radiation, e.g. optical sensing; by corpuscular radiation by scanning of the records by radiation in the optical part of the electromagnetic spectrum
- G06K7/10821—Methods or arrangements for sensing record carriers, e.g. for reading patterns by electromagnetic radiation, e.g. optical sensing; by corpuscular radiation by scanning of the records by radiation in the optical part of the electromagnetic spectrum further details of bar or optical code scanning devices
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Abstract
The present invention provides a kind of multiple continuous automatically identifying and reading methods of colour developing type micro-array biochip transmission signal values, identification reading instrument and recognition system for realizing this method.The feature of the reading method has：(1) scanning glass chip bar code is to obtain chip bar code information；(2) it is located at the glass-chip both sides for the principal phase machine of shooting chip image and for the background light source of principal phase machine illumination；(3) according to the bar code information, chip image and signaling point identification parameter, automatic identification and positioning signal point, the coordinate for obtaining the signaling point automatically；(4) signal value of signaling point is obtained automatically according to the coordinate of the signaling point of acquisition；(5) multiple chips (can be different types of chip) realize automatically continuously recognition by position movement.
Description
Technical field
Identification reading instrument and recognition system the present invention relates to a kind of biochip reading method, for realizing this method, specifically
Ground, it is related to a kind of method of multiple continuous automatically identifying and readings of colour developing type micro-array biochip transmission signal values, for realizing the party
The identification reading instrument and recognition system of method.
Background technology
Micro-array biochip is the mode with lattice arrangement on glass substrate, silicon chip or high polymer material substrate etc.
Synthesis or a series of fixed polymer, such as oligonucleotides, polypeptide and antibody etc..These polymer can be fluorescently labeled
Thing, chemical colour reaction class label are marked so as to by optical detection.Colour developing type micro-array chip is usually using digoxin, peppery
The polymer being fixed on chip is marked the chemical colour reaction class label such as root peroxidase, biotin, so as to quilt
Biochip identification reading instrument distinguishes its reaction result information.The characteristics of colour developing type micro-array biochip is that array point quantity is more, core
Piece reaction result need all array points on composite chip response situation carry out com-parison and analysis, visually can not accurate judgement array
The colour developing result of point.
Colour developing type micro-array biochip identification reading instrument is that the experimental result of colour developing type biochip is scanned and analyzed
Equipment.Typical colour developing type micro-array biochip identification reading instrument includes light source, possesses readding for CCD (charge coupling device) cameras
Read unit, CCD controllers, for carrying and load units of control chip stepping and for analysis chip recognition result
Computer.After CCD (charge coupling device) cameras obtain colour developing type micro-array biochip image under light source irradiation, pass through number
Shown on computers according to interface, by the position of array point that is installed in the software identification chip image on computer and
The signal value of array point.
Array point peripheral region the having occasionally there are dust, fiber, background etc of colour developing type micro-array biochip
The pollutant of certain signal value, coordinate setting and accurate collection signal value that can be to signaling point produce interference.Current colour developing type
Micro-array biochip identification reading instrument usually requires the type of the manual confirmation chip, is then manually adjusted in the software of computer
To find correct array point, automaticity is low, and efficiency is low；When needing to distinguish polytype biochip, manually
The efficiency of recognition can be lower, and manual confirmation chip type has the possibility slipped up by the increase of working strength, and then
Chip results recognition accuracy rate is caused to decline；The signal value of collection is usually led due to above-mentioned chip pollutant and manual operation
Cause interference distortion；In chip signal collection link, typically light is irradiated in backlight after passing through chip, and backlight reflects
Chip signal and then collected, and interference of the dust accumulated in backlight to signal value is very big, will also result in the signal of collection
Distortion；One-time detection 1 opens chip, and detection flux is low.
Accordingly, it is desirable to be able to develop the method that high accuracy, high flux, the colour developing type biochip of high automation are distinguished
And identification reading instrument.
The content of the invention
The present invention is completed, and it is an object of the present invention to provide a kind of high accuracy, high flux, height automate to solve the above problems
Micro-array biochip reading method, identification reading instrument and recognition system for realizing this method.
The present invention includes herein below：
(1) a kind of multiple continuous automatically identifying and reading methods of colour developing type micro-array biochip transmission signal values, its feature exist
In, including：
(a) by recognizing apparatus automatically scanning glass-chip bar code to obtain chip bar code information, the bar code information bag
Include gene loci, the line number of chip array point, columns, the columns and serial number of chip index point of chip detection；
(b) recognizing apparatus is obtained by the background light source positioned at beneath chips by the principal phase machine above the chip
Transmissive glass chip and the transmission detection image formed；
(c) according to the bar code information and chip detection image, recognizing apparatus automatic identification and positioning signal point, obtain automatically
Take the coordinate of the signaling point；
(d) according to the coordinate of the signaling point of acquisition, recognizing apparatus obtains the signal value of signaling point automatically, and the signal value is
The difference of the light transmittance of light transmittance and the signaling point ambient background on signaling point；
(e) chip bar code and signal value are associated；
(f) by recognizing apparatus moving chip, the automatic continuous of multiple chips (can be different types of chip) is realized
Recognition；
(g) each chip bar code and corresponding signal value are transmitted to computer and analyzed, and output result.
(2) method described in (1) as described above, it is characterised in that before identification and positioning signal point, recognizing apparatus is to obtaining
The chip image obtained carries out image procossing automatically.
(3) method described in (2) as described above, it is characterised in that described image processing includes：
Original image is cut out, takes out imaging moiety；
Brightness normalized is carried out to image；
Inverse and binary conversion treatment are carried out to image；With
Corroded or expand removal noise.
(4) method any one of (1) to (3) as described above, it is characterised in that the identification and positioning signal point
Step includes：
All points for having signal are searched for by recognizing apparatus；
By the size of the signaling point defined in size, shape, distribution and the position of the point searched and configuration file unit,
Shape, distribution and position are compared；
Selection meets the point that signaling point defines；
Output signal point coordinates.
(5) it is a kind of for realizing multiple continuous automatically identifying and reading methods of colour developing type micro-array biochip transmission signal values
Identification reading instrument, it is characterised in that including：
Shooting unit, for obtaining chip bar code information, shooting chip to obtain chip detection image；
Configuration file unit, for reading the parameter of relevant signaling point identification positioning and value in configuration file；
Signaling point identifies positioning unit, for according in bar code information, chip detection image and configuration file unit
Parameter, is identified and positioning signal point is to obtain the coordinate of signaling point；And
Signaling point value unit, for obtaining the signal value of signaling point, the signal value be light transmittance on signaling point with
The difference of the light transmittance of the signaling point ambient background.
(6) identification reading instrument described in (5) as described above, it is characterised in that the shooting unit include principal phase machine, parafacies machine and
For the background light source of principal phase machine illumination, the principal phase machine and the background light source are respectively positioned at the both sides of the chip.
(7) identification reading instrument described in (5) or (6) as described above, it is characterised in that the signaling point value unit also includes image
Alignment unit, the directionality for carrying out backlight to the chip image are calibrated and the gamma value of sensor are calibrated.
(8) identification reading instrument described in (5) or (6) as described above, it is characterised in that the identification reading instrument also includes carrying multiple chips
Carrying disk.
(9) identification reading instrument described in (5) or (6) as described above, it is characterised in that the identification reading instrument also includes being arranged at identification reading instrument
Screen on cabinet, for chip bar code information described in preview and the chip detection image.
(10) a kind of multiple continuous automatically identifying and reading methods for being used to realize colour developing type micro-array biochip transmission signal values
Recognition system, it is characterised in that including：
Identification reading instrument any one of above-mentioned (5)~(9), the colour developing type micro-array biochip for being provided with bar code and
Computer, wherein, analysis software is pre-installed in computer, by each chip bar code information exported in identification reading instrument and corresponding signal value
Matched with analysis software to obtain examining report.
Technique effect
Compared with prior art, multiple continuous automatically identifying and reading methods of colour developing type micro-array biochip of the invention, use
In the identification reading instrument and recognition system for realizing this method improve recognition colour developing type micro-array biochip result accuracy and from
Dynamicization degree, it is possible to achieve the high throughput analysis of colour developing type micro-array biochip.
The present invention on chip by designing bar code, the special parafacies machine of scanning barcode being set in identification reading instrument so that knows
Type information (including chip institute's test sample this model, array dot position information, the index point of chip to be measured can be automatically obtained by reading instrument
Positional information, signal value distributed intelligence etc.)；By setting configuration file unit, signaling point to identify that positioning unit and signaling point take
Value cell, with reference to acquired chip type information, each signaling point is automatically looked for so as to accurate, exports institute automatically
Distinguish the type information and signaling point information of chip；By designing the locomotive function to chip for recognizing apparatus so that recognition is set
It is standby can liaison distinguish multiple chips；Realize colour developing type micro-array biochip transmission signal values whole-course automation recognition and
High flux is distinguished.
The present invention identifies that positioning unit compares the profile of the signal that searches, position by the signaling point of identification reading instrument
It is right, the signal dot profile not in signaling point size range, in the range of site error is abandoned, the pollutants such as dust can be excluded
Interference, improve the degree of accuracy of recognition.
The present invention for the principal phase machine of shooting chip image and for the background light source that principal phase machine illuminates by will be placed in core
The both sides of piece, after light source irradiates chip, shooting unit obtains the transmission image of chip, anti-compared to common shooting chip backlight
Image is penetrated, backlight pollutant interference distortion to caused by signal acquisition in light reflection process is avoided, improves recognition
The degree of accuracy.
In a word, the present invention realize the whole-course automation to colour developing type micro-array biochip transmission signal, high accuracy,
The technique effect of high flux recognition.
Brief description of the drawings
Fig. 1 is the stream of multiple continuous automatically identifying and reading methods of the colour developing type micro-array biochip transmission signal values of the present invention
Cheng Tu.
Fig. 2 is the identification reading instrument module frame chart for being used to realize the above method of the present invention.
Fig. 3 is the identification reading instrument internal structure schematic diagram for being used to realize the above method of the present invention.
Embodiment
The invention mainly comprises multiple continuous automatically identifying and reading methods of colour developing type micro-array biochip transmission signal values, use
In the identification reading instrument and recognition system of realizing methods described.
The present invention is described in detail individually below, but the present invention is not limited to these contents, those skilled in the art
Various rational changes can be carried out to the present invention in the range of the invention thought of the present invention is not departed from.
Multiple continuous automatically identifying and reading methods of one, colour developing type micro-array biochip transmission signal values
Fig. 1 is the stream of multiple continuous automatically identifying and reading methods of the colour developing type micro-array biochip transmission signal values of the present invention
Cheng Tu, as shown in figure 1, multiple continuous automatically identifying and reading methods of colour developing type micro-array biochip transmission signal values include following step
Suddenly：
(i) the 1st glass-chip bar code of the shooting unit automatically scanning of recognizing apparatus is to obtain chip bar code information；
(ii) shooting unit of recognizing apparatus obtains the transmission image of the 1st chip automatically；
(iii) image of the 1st chip is handled；
(iv) according to the bar code information and chip image, by recognizing apparatus automatic identification and positioning signal point, obtain automatically
Take the coordinate of the signaling point；
(v) signal value of signaling point, the signal value are obtained automatically by recognizing apparatus according to the coordinate of the signaling point of acquisition
It is the difference of light transmittance on signaling point and the light transmittance of the signaling point ambient background；
(vi) the 1st chip bar code and signal value are associated；
(vii) recognizing apparatus is connected automatically by moving chip to multiple chips (can be different types of chip)
Continuous recognition；
(viii) each chip bar code information and signal value of acquisition are transmitted and carried out into computer by recognizing apparatus automatically
Matching, obtain testing result.The bar code information includes gene loci, the line number of chip array point, columns, the core of chip detection
The columns and serial number of piece index point.
Described image processing includes：Original image is cut out, takes out imaging moiety；Brightness normalization is carried out to image
Processing；Inverse and binary conversion treatment are carried out to image；And corroded or expand removal noise.
The step of automatic identification and positioning signal point of the present invention, includes：Recognizing apparatus searches for all signaling points automatically；
The size of signaling point defined in the size of the signaling point searched, position and configuration file unit, position range are compared
Compared with；Selection meets the point that signaling point defines；Output signal point coordinates.
The step of signal value of the automatic acquisition signaling point of the present invention, includes：Recognizing apparatus calculates whole signaling point area automatically
Background signal value (i.e. overall background value) at the non-signal point of domain；Calculate local background's signal value on each signaling point periphery (i.e.
Local background is worth)；Calculate signaling point light transmittance values；Calculate signaling point signal value.
Two, are used for the identification reading instrument for realizing multiple continuous automatically identifying and reading methods of colour developing type micro-array biochip transmission signal values
The identification reading instrument of the present invention is used for multiple companies for the colour developing type micro-array biochip transmission signal values for realizing the present invention
Automatically identifying and reading method is read, and the signal value of acquisition is exported to computer.
Fig. 2 is the structural representation of the colour developing type micro-array biochip identification reading instrument of the present invention.It is as shown in figure 1, of the invention
Identification reading instrument mainly include shooting unit 1, configuration file unit 2, signaling point identification positioning unit 3 and signaling point value unit 4.
Fig. 3 is the internal structure schematic diagram of the colour developing type micro-array biochip identification reading instrument of the present invention.With reference to Fig. 2 and
The identification reading instrument of the present invention is described in detail Fig. 3.
Shooting unit 1 is used to obtain chip bar code information and shooting chip is to obtain chip image.As shown in figure 3, shooting
Unit 1 further comprises principal phase machine 11, parafacies machine 12, background light source 13 and parafacies machine lighting source for the illumination of principal phase machine
15.Principal phase machine 11 is used for shooting chip image, and parafacies machine 12 is used to scan chip bar code.Preferably five mega pixels of principal phase machine 11
CCD camera, parafacies machine 12 are not particularly limited, common industrial camera.The 13 preferred LED of background light source of principal phase machine illumination
Light source, parafacies machine lighting source 15 is it is also preferred that LED light source.
Shooting unit 1 preferably also includes CMOS (complementary metal oxide semiconductor) gray level image sensor.
It is preferred that the principal phase machine 11 and the background light source 13 are located at the both sides of the chip, principal phase machine 11 faces to be checked
Chip is surveyed, such as can be in the surface of chip, the background light source 13 of principal phase machine is located at the back side of chip to be detected.Parafacies machine 12
The barcode position of chip to be detected is faced, such as can be in the surface of chip bar code.
The bar code that the identification reading instrument of the present invention scans biochip by the parafacies machine 12 of shooting unit 1 first obtains chip strip
Code information, according to the bar code information, the base that the corresponding model of chip, the ranks number of array point and chip detect can be obtained
Because of information such as site, the columns of chip index point and serial numbers.Then the chip is shot by the multiexposure, multiple exposure of CCD principal phases machine 11,
Obtain final chip image.
Configuration file unit 2 is used to read signaling point identification positioning and the configuration needed for signaling point value from configuration file
Parameter.Signaling point identification positioning and the relevant configured parameter needed for value defined in configuration file, including signaling point identification rule
Then, backlight calibration value and pick up calibration value.
The parameter that the configuration file unit of the present invention provides is as shown in table 1.
Table 1：Configuration parameter in configuration file
| Parameter area | Explanation |
| 10.0~30.0 floating-points | Signaling point average headway, unit are pixel |
| 0.0~5.0 floating-point | Signaling point interval error permissible value, unit are pixel |
| 3~10 integers | Signal spot size minimum value, unit pixel |
| 10~20 integers | Signaling point dimensional maximums, unit pixel |
| 80~100 integers | The minimum signal value that signaling point allows |
| 300~450 integers | The maximum signal level that signaling point allows |
| 200~350 shapings | Index point signal value scope |
| 0.0~1.0 floating-point | The nonqualifying pixels ratio allowed in signaling point |
| 0~100 integer | The statistics accounting of background value pixel |
| 0/1 boolean | Background value uses average value or maximum, 0 average value, 1 maximum |
| 0.0~200.0 floating-point | Sensor signal value calculates the correction coefficient of light transmittance |
| 0 shaping | Output valve is 0 when signal value is less than this value |
| 0/1 boolean | Global using local background or global context, 0,1 is local |
| 1~10 integer | The signaling point line number of the chip of model [n], [n] are three 10 system numbers |
| 1~10 integer | The signaling point columns of the chip of model [n], [n] are three 10 system numbers |
Configuration parameter can also increase the signal value distributed constant of different chips, i.e. chip each position (specific row, column, seat
Mark) signaling point span, exclude interference signal not in the range of signal value, improve the accuracy of signaling point identification.
Signaling point identification positioning unit 3 is used to identify and positioning signal point is to obtain the coordinate of signaling point, specifically, signal
Set in chip bar code information, chip image and configuration file unit 2 that point identification positioning unit obtains according to shooting unit 1
Signaling point recognition rule, the minimum value and maximum of signaling point ranks and signal dot profile (size), have to what is searched
The size of the point of signal, position are compared, and exclude the point that position, size do not meet signaling point recognition rule, and by spacing with
Sizeable point is screened, and identifies the signaling point in image, and all signaling points are positioned, and with XY coordinates
Form exports.
Signaling point identification positioning unit 3 preferably further has graphics processing unit, for all array click-through
Image is handled before row search.Specifically, graphics processing unit is cut to original image first, takes out imaging section
Point, then brightness normalization, inverse, binaryzation are carried out to image, then remove noise using once corrosion/expansion.
It is summed up, the preferable workflow of signaling point identification positioning unit 3 is：First, the information such as image are read in, so
Afterwards, image, normalization, inverse, binaryzation, corrosion/expansion, final search array point, screening signaling point, positioning signal are cut
Point, output signal point coordinates.
In actual use, dust present on chip etc. can be also imaged on photo, can be taken during contouring after binarization
To the profile of these dusts, recognition can be influenceed by dust can not normal value, so as to the coordinate setting mistake to signaling point.This
Invention identifies that the profile that searches, position are compared positioning unit by using signaling point, will not be in signal size range
Profile in the range of interior, site error is given up, and so as to exclude the influence to signal point location such as dust, it is accurate to improve identification
Degree.
Signaling point value unit 4 is used to read the signal value in image on signal point position, and the signal value is signaling point
The difference of upper light transmittance and periphery background light transmittance.Specifically, first calculated during calculating at the non-signal point of whole signaling point region
Background signal value, record its average and maximum.Local background's signal value on each signaling point periphery is calculated again, and it is equal also to record its
Value and maximum.The light transmittance values of all pixels in whole signaling point region are obtained, removal wherein exceedes the normal printing opacity of signaling point
The pixel of scope, rest of pixels are averaged, and obtain the light transmittance average value of signaling point.Finally the light transmittance values of signaling point are subtracted
Background value selected in configuration file is removed, obtains the signal value of signaling point herein.
The relation for the light transmittance that the signal value of chip signal point collects with CCD principal phases machine 11 is as follows：100% is saturating after calibration
Light rate benchmark sampled signal values are 138, and imaging sensor sampled value scope is 0~255 totally 256 grades.Signal value is 16 samplings
Value passes through what is be calculated：
Wherein, Val is signal value, SiFor signaling point light transmittance, BiFor background light transmittance, k is backlight correction coefficient (0<k≤
2)。
As needed, signaling point value unit of the invention preferably further includes image calibration unit, for photo
Carry out the directionality calibration of backlight and the Gamma of sensor is calibrated.
Because in actual use, exist sometimes identification reading instrument backlight it is uneven the problem of, so as to influence to believe
The value of number point, produce value error.The uneven degree and back light uniform in material for being often as backlight of this backlight
Directionality, cause backlight illumination to be changed on X/Y directions.By further setting image calibration unit, to backlight
The directional change of brightness adds penalty coefficient, ensures backlight illumination uniformity during value, and value control errors are being wanted
In the range of asking.
In addition, there may come a time when that meeting is variant between light ray energy and output valve that sensor is received due to manufacture reason,
It is possible to causing the determination of light transmittance linearity bad, error may be produced in signaling point value.Image calibration unit can
To carry out Gamma (gamma) calibrations to the value of sensor, its linearity is improved, by value control errors in desired scope
It is interior.
As needed, identification reading instrument of the invention can also have information output unit.Information output unit, which is used to export, to be believed
Number point information and inverse exhibiting pictures, specifically, signal point position information and signaling point value information are saved as into text text
Part, and signaling point region is taken out to the exhibiting pictures for saving as the high contrast of inverse.
Above-mentioned configuration file unit 2, signaling point identification positioning unit 3 and the signaling point value unit 4 of the present invention can also
A signaling point recognition unit is assembled to realize.
The identification reading instrument of the present invention also includes mobile carrying disk 51, guide rail 52 and the electric motor 53 for carrying multiple chips.Institute
State carrying disk 51 and include multiple biochip grooves arranged in parallel, drive carrying disk 51 to load the lattice of one lattice of chip one by motor 53
Motion, when chip is in the underface of CCD principal phases machine 11 and chip bar code is in parafacies 12 underface of machine, stop motion.Pass through
The chip detection image that the transmission of LED background light sources 13 is formed utilizes big visual field focal plane by more than 11 sampling of taking pictures of CCD principal phase machines
Adjustment technology and Techniques of Automatic Focusing control image quality.Parafacies machine 12 is using parafacies machine lighting source 15, to biochip bar
Code region is scanned sampling.
The identification reading instrument of the present invention also includes the screen being arranged on identification reading instrument cabinet, and the screen is LCD screen, for preview institute
State chip bar code information and the chip image.
The circuit of the identification reading instrument of the present invention mainly includes Switching Power Supply, mainboard, core board, secondary camera board, main camera board, connect
Oralia, position sensor plate, background tabula rasa, motor driving plate, key indicator lamp plate, LCD etc..
The function of each several part is as follows：
Switching Power Supply：Support the input of 110~240V AC Width funtions
Core board：Using IMX6 primary processors, there is powerful data-handling capacity
Secondary camera board：For shooting bar code
Main camera board：Shooting for biochip
Mainboard：Power supply processing and core board are carried out to each feature board control logic and feedback
Position sensor plate：The rz signal of motor range position
Bias light 1：LED backlight plate, background illumination when for main camera shooting chip
Bias light 2：Branch LED, background illumination when bar code is shot for secondary camera
Motor driving plate：For driving the phase step motor of 4 line system 2
Button and indication LED：Function button when being used for machine
Interface board：Integration USB and Internet RJ45 interfaces
The present invention identification reading instrument also include each part between and the data-interface between computer.
Sum up, the mode of operation of identification reading instrument unit of the invention is as follows：
Drive carrying disk that biochip to be detected is transported into the position for being adapted to shoot, Ran Houyou by electric motor first
The secondary camera scanning chip bar code of shooting unit and by principal phase machine shooting chip image, then identifies positioning unit root by signaling point
According to the signaling point identification parameter in bar code information, chip image and configuration file unit, identify and positioning signal point is to obtain
The coordinate of signaling point, next by signaling point value unit according to the letter in the coordinate information and configuration file unit of signaling point
The signal value of number point value parameter acquiring signaling point, finally exports the signal value of signaling point to external computer.
In addition, in configuration file unit, configuration file is needed to test a variety of parameter inputs, and model is inputted beyond parameter
The needs prompting warning enclosed, all test results need the test oracle for meeting definition.In signaling point fixation and recognition unit and
Signaling point value unit, it is also desirable to test the input of various different range, the setting in configuration file, obtain with inputting phase
Corresponding result, for the data beyond input range, to prompt to alert.
Pass through the identification reading instrument of the present invention, it is possible to achieve multiple are continuous automatic for colour developing type micro-array biochip transmission signal values
The method of recognition.
The identification reading instrument of the present invention is not required to the analysis software by external computer, and independent can realizes obtaining for signal value
Take.
The recognition system of three, colour developing type micro-array biochips
Present invention additionally comprises for realizing multiple continuous automatically identifying and reading sides of colour developing type micro-array biochip transmission signal values
The recognition system of method.The recognition system of the present invention includes the colour developing type micro-array biochip through particular design, for obtaining core
The identification reading instrument and computer of piece signal value.
1. the colour developing type micro-array biochip through particular design
In order to improve the degree of accuracy of identification, the present invention has carried out specific set to the colour developing type micro-array biochip of routine
Meter, is provided with index point and bar code on chip.
The present invention is in high order end of the chip lattice array per a line, setting one or more columns per page index point, preferably 3 row.The mark
Point is a kind of positive control probe, with the reaction containing the oligonucleotide sequence that can be completely combined with the probe sequence of the index point
Hybridization reaction occurs for liquid, produces stable colour developing result, shows stronger signal value in the detection.For example, in genetic chip,
Index point composition includes specific nucleotide sequence, has the sequence matched completely with index point nucleotides in reaction solution, therefore can
Stably to combine and develop the color.The adding method of index point is identical with other probe point methods, can pass through commercially available biochip
Point sample equipment is added.
The function of index point is exactly the function of general positive control, when index point signal value is normal, illustrates to be developed the color
Reaction, that is, illustrate add testing sample there occurs hybridization reaction with chip array point.In the present invention, because index point reacts
Signal value is not only stablized but also stronger than the signal value of in general reflecting point afterwards, when to chip image seek, according to configuration
Parameter first looks for index point, it is determined that mark point coordinates after further according to known array point distribution ranks number, spacing distance or
The relative coordinate of each array point, extrapolates each array point coordinates value.Because index point signal value by force and stably, first looks for indicating
Point rather than other array points, the accuracy for ensureing to find array point can be maximized.
The bar code for identifying the chip type is provided with the colour developing type micro-array biochip of the present invention.By scanning this
Code, the relevant information of chip to be measured, including the line number of chip type, chip array point, columns, point spacing, each battle array can be obtained
Arrange relative coordinate, signal Distribution value (the signal value scope of specific array point, such as the signal value model of index point of array point of point
Enclose) etc. information.
Bar code is common bar code, and the left or right of chip can be arranged on for example, by the mode of stickup.
2. the identification reading instrument for obtaining chip signal value
Identification reading instrument is colour developing type micro-array biochip identification reading instrument described under above-mentioned (two) item.Identification reading instrument has and meter
Data-interface between calculation machine.
3. computer
Analysis software is installed, software is not particularly limited, and can select for example commercially available Arrray in computer
The Doctor groupwares (Shanghai Bioon Technology Co., Ltd.), the chip of acquisition is detected by data (biology by the software
The coordinate distributed intelligence of chip signal point and signal value) matched with the analyzing biochips APMB package in software and export inspection
Observe and predict announcement.
Computer is connected by USB data line and Ethernet interface with identification reading instrument.
The recognition system of the present invention also includes the function that reports an error after recognition failure, data preserve and printing function, really real
The whole-course automation of colour developing type micro-array biochip superframe signal recognition is showed.
Embodiment 1
Colour developing type micro-array biochip to be measured is put into the chip slot of carrying disk 51 of identification reading instrument, can once be put
Enter 8, drive the lattice of 51 1 lattice of carrying disk one to move by motor 53, when the 1st chip to be measured be in the underface of CCD principal phases machine 11,
When chip bar code is in parafacies 12 location directly below of machine simultaneously, stop motion.Using parafacies machine lighting source 15, pass through parafacies
Machine 12 carries out sampling of taking pictures to chip bar code region.The chip detection image formed by the transmission of principal phase machine LED background light sources 13
By more than 11 sampling of taking pictures of CCD principal phase machines, chip image is obtained.
Then, graphics processing unit is first cut out to the original image of chip, takes out imaging moiety, then image is carried out
Brightness normalized, inverse and binary conversion treatment then are carried out to image, then once corroded/expanded removal noise.
Then, signaling point identification positioning unit 3 scans for chip image, all signal spot sizes that will be searched
It is ranked up, according to the minimum value and maximum of the size set in configuration file unit, filters out the point for meeting size range.
The signal value scope of index point has been preset in configuration file unit, the signal value of index point is big compared with General reactions point, easily distinguishes,
Therefore in signal dot profile screening process, first index point is screened according to index point signal value scope, further according to default
Point distance values and ranks number to other wide screenings of click-through road wheel, which improves the accuracy of array point identification.And according to
Default spacing and chip ranks number are positioned, the noise spot such as out contaminants, export the coordinate letter of all signaling points
Breath.
Then, the coordinate information by signaling point value unit 4 according to all signaling points of output, whole letter is calculated respectively
Background signal value, local background's signal value on each signaling point periphery at number point region non-signal point, signaling point light transmittance values,
Then above-mentioned numerical value is substituted into aforementioned formula (1) and calculates each signaling point signal value, associate the 1st chip bar code and signal value.
Next, carrying disk 51 moves a lattice, the 2nd chip to be measured is set to be in immediately below principal phase machine 11, while chip strip
Code is in the location directly below of parafacies machine 12, repeats the operation same with above-mentioned 1st chip to be measured, the 2nd chip of completion
Signaling point value.
Aforesaid operations are repeated, to the signaling point value for completing all chips.
Finally, the signal value of above-mentioned each chip bar code and signaling point is exported to computer and analyzed, output detection
Report.
Embodiment 2
In addition to signaling point identification positioning unit 3 is using following scheme, remaining is the same as embodiment 1.
The array point coordinates value of chip has been preset in configuration file unit, all dot profile search in image have been completed
Afterwards, the coordinate of index point and default array point coordinates in image are determined according to index point signal value scope, calculates index point
Array point coordinates in addition, array point is identified as in a range of point of coordinate extrapolated, in the certain model of projected coordinate
Enclose outer point and be then identified as the noise spot caused by the factors such as pollution, when occurring multiple points in institute's projected coordinate certain limit
When, the profile and the difference of array dot profile and the size of point of points of contamination can be combined, is identified, and then improves array point and knows
Other order of accuarcy, finally determine coordinate and the output of each array point.
Claims (10)
1. a kind of multiple continuous automatically identifying and reading methods of colour developing type micro-array biochip transmission signal values, it is characterised in that bag
Include：
(a) by the parafacies machine automatically scanning glass-chip bar code of recognizing apparatus to obtain chip bar code information, and by positioned at
Principal phase machine above the chip obtains the transmission detection formed by the background light source transmissive glass chip positioned at beneath chips
Image；
(b) according to the bar code information and chip detection image, by recognizing apparatus automatic identification and positioning signal point, automatic acquisition
The coordinate of the signaling point；
(c) signal value of signaling point is obtained automatically by recognizing apparatus according to the coordinate of the signaling point of acquisition, the signal value is letter
The difference of the light transmittance of light transmittance and the signaling point ambient background on number point；
(d) chip bar code and signal value are associated；
(e) by recognizing apparatus moving chip, multiple chips are automatically continuously distinguished；
(f) each chip bar code and corresponding signal value are transmitted to computer and analyzed, and output result.
2. the method as described in claim 1, it is characterised in that before identification and positioning signal point, recognizing apparatus is automatically right
The chip image of acquisition carries out image procossing.
3. method as claimed in claim 2, it is characterised in that described image processing includes：
Original image is cut out, takes out imaging moiety；
Brightness normalized is carried out to image；
Inverse and binary conversion treatment are carried out to image；With
Corroded or expand removal noise.
4. method as claimed any one in claims 1 to 3, it is characterised in that described the step of identifying simultaneously positioning signal point
Including：
Recognizing apparatus searches for all points for having signal automatically；
The size of signaling point defined in the size of the point for having signal searched, position and configuration file unit and position are entered
Row compares；
Selection meets the point that signaling point defines；
Output signal point coordinates.
A kind of 5. colour developing type micro-array biochip identification reading instrument, it is characterised in that including：
Shooting unit, for obtaining chip bar code information and shooting chip is to obtain chip image；
Configuration file unit, for reading the parameter of relevant signaling point identification positioning and value in configuration file；
Signaling point identifies positioning unit, for the parameter in bar code information, chip image and configuration file unit, identification
And positioning signal point is to obtain the coordinate of signaling point；And
Signaling point value unit, for obtaining the signal value of signaling point according to the coordinate of signaling point, the signal value is signaling point
On light transmittance and the signaling point ambient background light transmittance difference.
6. colour developing type micro-array biochip identification reading instrument as claimed in claim 5, it is characterised in that
The shooting unit includes principal phase machine, parafacies machine and the background light source for the illumination of principal phase machine, the principal phase machine and institute
State the both sides that background light source is located at chip to be detected respectively.
7. the colour developing type micro-array biochip identification reading instrument as described in claim 5 or 6, it is characterised in that the signaling point takes
Value cell also includes image calibration unit, for carrying out the directionality calibration of backlight to the chip image and to sensor
Gamma value is calibrated.
8. the colour developing type micro-array biochip identification reading instrument as described in claim 5 or 6, it is characterised in that the identification reading instrument is also
Carrying disk including carrying multiple chips.
9. the colour developing type micro-array biochip identification reading instrument as described in claim 5 or 6, it is characterised in that the identification reading instrument is also
Including the screen being arranged on identification reading instrument cabinet, for chip bar code information described in preview and the chip image.
A kind of 10. recognition system of colour developing type micro-array biochip, it is characterised in that including：
Colour developing type micro-array biochip identification reading instrument any one of claim 5~9, the colour developing type for being provided with bar code are micro-
Array bio-chip and computer, wherein, analysis software is pre-installed in computer, each chip bar code exported in identification reading instrument is believed
Breath and corresponding signal value are matched with analysis software to obtain examining report.
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| CN107254511A (en) * | 2017-04-27 | 2017-10-17 | 臻准生物科技（上海）有限公司 | A kind of digital pcr chip signal read method |
| CN108280385A (en) * | 2018-02-06 | 2018-07-13 | 佛山市南方数据科学研究院 | A kind of invisible two dimensional barcode solution read apparatus |
| CN110310334B (en) * | 2018-03-20 | 2023-05-16 | 深圳市华大智造软件技术有限公司 | Biochip positioning method, gene sequencer, system and storage medium |
| CN112995655A (en) * | 2021-03-04 | 2021-06-18 | 上海创功通讯技术有限公司 | Stray light inspection method and equipment |
| CN113850200B (en) * | 2021-09-27 | 2022-09-06 | 广东凯普科技智造有限公司 | Gene chip interpretation method, device, equipment and storage medium |
Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20030096224A1 (en) * | 1997-06-20 | 2003-05-22 | Ciphergen Biosystems, Inc. | Retentate chromatography and protein chip arrays with applications in biology and medicine |
| CN101681455A (en) * | 2007-04-23 | 2010-03-24 | 三星电子株式会社 | Remote medical-diagnosis system and method |
| CN102608130A (en) * | 2012-01-18 | 2012-07-25 | 西安麦诺兹视频科技有限公司 | Smart card stain detecting system based on image feature matching technology and detection and detecting method |
| CN105044108A (en) * | 2015-07-10 | 2015-11-11 | 港龙生物技术（深圳）有限公司 | Microarray chip sample application quality automatic judgment system and judgment method |
-
2015
- 2015-12-23 CN CN201510979230.1A patent/CN105590079B/en active Active
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20030096224A1 (en) * | 1997-06-20 | 2003-05-22 | Ciphergen Biosystems, Inc. | Retentate chromatography and protein chip arrays with applications in biology and medicine |
| CN101681455A (en) * | 2007-04-23 | 2010-03-24 | 三星电子株式会社 | Remote medical-diagnosis system and method |
| CN102608130A (en) * | 2012-01-18 | 2012-07-25 | 西安麦诺兹视频科技有限公司 | Smart card stain detecting system based on image feature matching technology and detection and detecting method |
| CN105044108A (en) * | 2015-07-10 | 2015-11-11 | 港龙生物技术（深圳）有限公司 | Microarray chip sample application quality automatic judgment system and judgment method |
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