CN206420887U - A kind of tumor markers group detection micro-fluidic chip - Google Patents

A kind of tumor markers group detection micro-fluidic chip Download PDF

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Publication number
CN206420887U
CN206420887U CN201720017398.9U CN201720017398U CN206420887U CN 206420887 U CN206420887 U CN 206420887U CN 201720017398 U CN201720017398 U CN 201720017398U CN 206420887 U CN206420887 U CN 206420887U
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reaction chamber
micro
tumor markers
blood sampling
flow path
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CN201720017398.9U
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尤晖
孙翠敏
尤翔
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Abstract

The utility model is related to a kind of tumor markers group's detection micro-fluidic chip, including substrate and the cover plate that is positioned above, sets blood sampling microneedle array on the cover plate, there is micro-pipe the inside of every blood sampling micropin;Both the cover plate and substrate are glued or thermocompression bonding forms spill cavity, sample cavity, reaction chamber, capillary flow path and waste liquid chamber, and the sample cavity is connected with reaction chamber on vertical space;Blotting paper and filter paper are set in the sample cavity;The reaction chamber is located at below filter paper, and micro-pillar array built in the reaction chamber, the bottom surface of reaction chamber and the surface of micro-pillar array scribble the labelled antibody for being coupled chromophoric group;The bottom of the end edge region of the capillary flow path sets the multiple test strips and quality control band for being printed on immobilised antibody reagent.The utility model realizes self-service detection, without the auxiliary of professional equipment, person under inspection's Self-operating;Blood sampling volume is extremely low, it is only necessary to a drop finger tip blood, it is possible to while detecting Diagnostic Value of Several Serum Tumor Markers index.

Description

A kind of tumor markers group detection micro-fluidic chip
Technical field
The utility model is related to micro-fluidic and tumor screening technical field, and especially a kind of tumor markers group is detected with micro- Fluidic chip.
Background technology
China's Cancer Mortality increasingly rises, and seriously threatens people's health.Tackling the Best strategy of tumour threat is " early discovery, early treatment "." early to find " is the premise of " early treatment ", and cure rate will be greatly improved, or patient and society save Save substantial amounts of medical expense.Tumor screening is the important channel of early detection cancer and precancerous lesion, popularizes tumor screening, Early diagnostic rate is improved, is the main effective means of diagnosis and treatment malignant tumour.
At present, tumor screening is typically detected using low-dose CT scanning or blood serum tumor markers, is both needed to certain Carried out in the medical institutions of scale, completion is operated in special instrument by possessing the professional and technical personnel of corresponding qualification, it is impossible to Cities and towns and rural area are carried out extensively.Higher price is also difficult to benefit low-income group, constrains the popularization of tumor screening work.
Utility model content
The purpose of this utility model is that providing one kind detects quick, low cost, without special instrument, realizes self-service Tumor markers group's detection micro-fluidic chip of formula detection.
To achieve the above object, the utility model employs following technical scheme:A kind of tumor markers group is detected with micro- Fluidic chip, including substrate and the cover plate that is positioned above, the cover plate are to set blood sampling micropin on transparent material, the cover plate Array, the blood sampling microneedle array is made up of multiple blood sampling micropins, and there is micro-pipe the inside of every blood sampling micropin;The cover plate and base Both plates are glued or thermocompression bonding forms spill cavity, sample cavity, reaction chamber, capillary flow path and waste liquid chamber, the sample cavity and Reaction chamber is connected on vertical space, and sample cavity is upper, and reaction chamber is under;Blotting paper and filter paper are set in the sample cavity;Institute Reaction chamber is stated below filter paper, micro-pillar array built in the reaction chamber, the bottom surface of reaction chamber and the surface of micro-pillar array are scribbled It has been coupled the labelled antibody of chromophoric group;The capillary flow path is connected by time-delay valve with reaction chamber;The capillary flow path The bottom of end edge region set and be printed on the multiple test strips and quality control band of immobilised antibody reagent, each inspection Surveying band is used to detect a kind of tumor markers;Outside the capillary flow path, with a pair of test strip and quality control band 1 Standard detection colour band and standard quality control colour band are printed at the position answered.
The blood sampling microneedle array is made by the processing technology of microelectromechanical systems, and built-in microchannel connects with sample cavity It is logical.
The blotting paper and the bottom of the micro-pipe in blood sampling micropin are closely coupled;The filter paper be located at blotting paper lower section, The top of reaction chamber.
Connected between the top of the sample cavity and spill cavity by overflow launder.
The time-delay valve is one section long about 5 millimeters of the capillary between reaction chamber and capillary flow path, its bottom surface With hydrophobic property.
As shown from the above technical solution, the beneficial effects of the utility model are:First, realize self-service detection:Need not It is in hospital, without the auxiliary of professional equipment, person under inspection's Self-operating, self-examination;Second, blood sampling volume is extremely low:A drop is only needed to refer to Sharp blood, it is possible to while detecting Diagnostic Value of Several Serum Tumor Markers index;3rd, high flux:Same capillary flow path, can once be detected Diagnostic Value of Several Serum Tumor Markers;4th, the visualization of tumor markers index is read, without the optical device equipment such as exciting;5th, height Integrated, precision:Only with a runner, only a kind of chromophoric group is used, so that it may synchronous detection multi-tumor Markers, without many colour codes Note;6th, the quantitative detection of tumor markers:Designed by exquisite overflow launder and spill cavity, realize accurate quantification sample introduction, again Using the contrast of test strip and standard detection colour band, the quantitative detection of Diagnostic Value of Several Serum Tumor Markers is realized, and improve the steady of detection Qualitative and reliability.7th, detection speed is fast:Whole detection process is only needed 15 minutes;8th, using MEMS blood sampling micropin battle arrays Row, take a blood sample safely, without pain;9th, the auto injection and conveying and flow velocity of blood serum sample are realized using capillary soakage principle Control, whole process is without extraneous control or provides energy, without using any other equipment;Tenth, chip is made of plastics, It is adapted to produce in enormous quantities, cost is extremely low, is adapted to disposable.
Brief description of the drawings
Fig. 1 is the structural representation of transparent cover plate in the utility model;
Fig. 2 is the structural representation of substrate and all parts installed thereon in the utility model;
Fig. 3 is sectional view of the present utility model;
Fig. 4 is the mplifying structure schematic diagram of two micropins in the utility model.
Embodiment
As shown in Figure 1, 2, 3, a kind of tumor markers group detection micro-fluidic chip, including substrate 1 and disposed thereon The cover plate 2 of side, the cover plate 2 is transparent material, sets blood sampling microneedle array 3 on the cover plate 2, the blood sampling microneedle array 3 by Multiple blood sampling micropin compositions, there is micro-pipe 14 inside of every blood sampling micropin;Both the cover plate 2 and substrate 1 gluing or hot pressing key Conjunction forms spill cavity 4, sample cavity 16, reaction chamber 5, capillary flow path 8 and waste liquid chamber 15, and the sample cavity 16 and reaction chamber 5 exist Connected on vertical space, sample cavity 16 is upper, and reaction chamber 5 is under;Blotting paper 6 and filter paper 18 are set in the sample cavity 16;Institute Capillary flow path 8 is stated to connect with reaction chamber 5 by time-delay valve 9;The bottom of the end edge region of the capillary flow path 8, which is set, to be printed on The multiple test strips 13 and quality control band 12 of immobilised antibody reagent, each test strip 13 are used to detect one kind Tumor markers;Outside the capillary flow path 8, with being printed at test strip 13 and the one-to-one position of quality control band 12 Standard detection colour band 10 and standard quality control colour band 11, join as detection reaction and the control of quality control response intensity is read Examine.
As shown in Figure 1, 2, the substrate 1 and cover plate 2 are bonded using glue, with leakage-preventing.The material of substrate 1 and cover plate 2 It is the plastics of bio-compatibility, cover plate 2 is transparent material.For suitable for producing in enormous quantities, substrate 1 and transparent cover plate 2 are used Injection or hot press forming technology production.
As shown in figure 4, the blood sampling microneedle array 3 is made by the processing technology of microelectromechanical systems, every blood sampling is micro- The height of pin is 300 microns, and base diameter is 250 microns, and tip diameter is 100 microns.The pressing blood sampling of detected person's finger is micro- Pin array 3, blood sampling micropin can wear out the cuticula and epidermis of finger, and blood can penetrate into micro-fluidic by the micro-pipe 14 in micropin Chip.Because blood sampling micropin size is small, any nerve is hardly contacted when being pierced into skin;After extraction, the pin left on skin Hole is minimum, and skin can heal quickly, will not cause wound infection, so this take a blood sample safely, without pain.
As shown in Figure 2,3, the blotting paper 6 and the bottom of the micro-pipe 14 in blood sampling micropin are closely coupled, to absorb from micro- The blood sample that pipe 14 penetrates into, and strengthen suction of the micro-pipe 14 to blood sample;The filter paper 18 in the lower section of blotting paper 6, reaction chamber 5 it is upper Side, to whole blood filtration, serum be can pass through, and flow into following reaction chamber 5, and haemocyte can not then be passed through.Blotting paper 6 compared with Thickness, with larger hole, water imbibition is strong, is connected with the micro-pipe 14 in blood sampling microneedle array 3, enhances micro-pipe 14 to finger tip blood Suction, improves blood sampling efficiency.Filter paper 6 is in the lower section of blotting paper 18, and relatively thin, hole is smaller, to whole blood filtration:Serum can Following reaction chamber 5 is flowed into through the hole of filter paper 6, haemocyte can not then be passed through.
As shown in Figure 2,3, connected between the top of the sample cavity 16 and spill cavity 4 by overflow launder 17.The sample introduction The side of chamber 16 sets overflow launder 17, connects spill cavity 4 so that overprimed blood sample can overflow into spill cavity 4, it is ensured that enter The volume accurate quantification of the blood sample of sample cavity.
As shown in Figure 2,3, the reaction chamber 5 is located at the lower section of filter paper 18, micro-pillar array 7, reaction chamber built in the reaction chamber 5 5 bottom surface and the surface of micro-pillar array 7 scribble the labelled antibody for being coupled chromophoric group.The serum of testing sample passes through filter paper 6 Flow into after reaction chamber 5, labelled antibody is dissolved down from the surface of the bottom surface of reaction chamber 5 and micro-pillar array 7, it is and to be measured in serum Albumen(Tumor markers)Immune response is played, firm Ag-Ab is formed and combines, so that being coupled on labelled antibody Chromophoric group is firmly adhered to tested albumen(Tumor markers)On, i.e. testing protein(Tumor markers)By chromophoric group mark Note, the condition of indispensability is provided for subsequent detection.
As shown in Figure 2,3, the time-delay valve 9 is 5 millimeters for one section of length between reaction chamber 5 and capillary flow path 8 Capillary.The bottom surface of this section of capillary is hydrophobicity, cause liquid infiltrate the pipeline bottom process it is slow, so as to play prevention Serum flows into " valve " effect of capillary flow path 8, it is ensured that blood serum sample stops enough long-times in reaction chamber 5, with fully complete Into testing protein(Tumor markers)With the immune response of labelled antibody, it is ensured that testing protein is marked by chromophoric group.By spy After fixed a period of time, the ttom of pipe of this section of capillary flow path 8 is by serum complete wetting, and surface covers liquid film, reforms into parent Water, the effect for hindering blood serum sample is lost, is opened equivalent to valve, blood serum sample can smoothly flow under capillary force traction Cross.
As shown in Figure 2,3, the capillary flow path realizes blood serum sample along the automatic of pipeline using capillary soakage principle Conveying, capillary force turns into power of the traction blood serum sample along microchannel.Whole process is without extraneous control or provides energy Amount.Can be by setting the hydrophilic, hydrophobic characteristic of the specific region of capillary flow path 8, control blood serum sample flows through position at the appropriate speed Some test strips 13 and the region of quality control band 12 in the tail end of capillary flow path 8, make testing protein(Tumor markers) Specific immune response needed for detection is fully completed, and ensures not playing hair of the albumen of specific immune response with attachment thereon Color base group flows to waste liquid chamber 15 with serum, does not end up at test strip 13 and the region of quality control band 12.
As shown in Fig. 2 the test strip 13 and quality control band 12 are located at the bottom of the end edge region of capillary flow path 8 Portion, is made by printing different antibody reagents respectively in the bottom of capillary flow path 8.These antibody reagents are colourless in itself, Gu The bottom of capillary flow path 8 is securely attached to after change, serum is met and rinses, will not also be come off from duct bottom.Blood serum sample stream When crossing test strip 13 and quality control band 12, specific testing protein in blood serum sample(Tumor markers)Respectively with these Immobilised antibody reagent plays specific immune response, different Ag-Ab combinations is formed, so as to be trapped in phase respectively On the test strip answered.Due to testing protein(Tumor markers)Contaminated in reaction chamber 5 by labelled antibody by chromophoric group Color, so test strip 13 shows the color of chromophoric group.Captured testing protein(Tumor markers)It is more, test strip 13 color is deeper, therefore, it can the gray value by measuring test strip 13 after reaction, to judge tumour in blood sample to be measured The concentration of mark.Each test strip 13 is containing specific detection antibody reagent, for capturing a kind of tumor markers.Although Different tumor markerses is marked in reaction chamber 5 by same chromophoric group, but due to the inner each test strip of capillary flow path 8 13 be pinpoint in advance, and enough intervals are left each other, and detects that antibody is firmly attached on runner bottom, so inspection Each test strip 13 is not obscured mutually during survey, and interval is kept between the colour band shown, can be with the position recognition detection of colour band Any tumor markers, so as to realize " runner, a kind of chromophoric group, while detecting Diagnostic Value of Several Serum Tumor Markers ".
As shown in Figure 2,3, outside capillary flow path 8, with test strip 13 and the one-to-one position of quality control band 12 Standard detection colour band 10 and standard quality control colour band 11 are printed on, as pair for reading detection reaction and quality control response intensity According to reference.Whether quality control band 12 is used for proofing chip effective:Such as fruit chip effectively, after blood serum sample flows through, quality control The color that colour band 12 processed occurs should control the color of colour band 11 to approach with standard quality, otherwise, then illustrate chip failure.To inspection Survey band 13, quality control band 12, standard detection colour band 10 and standard quality control colour band 11 and shoot digital photos, recycle Image processing software controls colour band 11, test strip 13 and standard detection colour band to quality control strip band 12 and standard quality respectively 10 carry out the gray value contrast in unit area, it can be determined that chip is detected whether effectively, and converses each test strip correspondence Tumor markers concentration.
Workflow of the present utility model is as follows:
1)Finger tip blood sample introduction:Blood sampling microneedle array 3 on detected person's finger pressing chip cover plate 2, microneedle of taking a blood sample The cuticula and epidermis of finger, blood can penetrate into the sample cavity 16 of chip by the micro-pipe 14 in micropin of taking a blood sample, by upper strata Filter paper 18 absorbs.Excessive blood sample flows into spill cavity 4 by overflow launder 17, it is ensured that enter the accurate quantification of the blood sample of reaction chamber 5.
2)Serum is separated:Finger tip blood is inhaled into after the upper strata filter paper in sample cavity 16, under gravity, through lower metafiltration Paper enters reaction chamber 5.The hole of lower floor's filter paper is small, and serum can be passed through, and flows into reaction chamber 5, and haemocyte can not then be passed through, stayed in On filter paper.
3)Testing protein(Tumor markers)Mark:The bottom of chamber and the surface of micro-pillar array 7 of reaction chamber 5 scribble and have been coupled color development The labelled antibody of group.Due to the effect of the time-delay valve 9 between reaction chamber 5 and capillary flow path 8, serum enters after reaction chamber 5, Stayed for some time in reaction chamber 5, by labelled antibody from the bottom of chamber of reaction chamber 5 and the surface of micro-pillar array 7 " dissolving ' under Come.Testing protein in serum(Tumor markers)Immune response is played with labelled antibody, so as to be marked by chromophoric group.
4)Testing protein is captured:After time-delay valve 9 is opened, serum flows along capillary flow path 8 automatically under capillary force action It is dynamic, test strip 13 and the region of quality control band 12 are flowed through at the appropriate speed.The bottom of test strip 13 is preprinted with can With tumor markers to be measured(Albumen)The antibody probe of specific reaction is played, that is, captures antibody.Capturing antibody should be with above-mentioned mark Remember antibody no cross reaction, and be securely attached to detect the bottom of reaction zone.When serum flows through, the tumour to be measured in serum Marker protein, it will play specific reaction with capture antibody, form Ag-Ab combination, so as to be attached to detection reaction The bottom in area.Due to tumor markers to be measured(Albumen)Chromophoric group is coupled, so occurring in the bottom of detection reaction zone Develop the color band.Other compositions in serum will flow into waste liquid chamber 15 along capillary channel.Solid phase is printed on quality control band 12 The Quality Control antibody of change, also can be with tumor markers to be measured(Albumen)Immune response is played, tumor markers to be measured is also captured(Egg In vain).Such as fruit chip reaction effectively, after blood serum sample flows through, quality control colour band 12 will develop the color, and otherwise, then illustrate chip failure.
5)Detection is read:Color is controlled to test strip 13, quality control band 12, standard detection colour band 10 and standard quality Band 11 is taken pictures, and then controls colour band 11, test strip 13 to quality control strip band 12 and standard quality using image processing software The gray value for carrying out unit area with standard detection colour band 10 is contrasted, and judges that chip is detected whether effectively, and converse each detection The concentration of the corresponding tumor markers of band.
In summary, the utility model realizes self-service detection:Without in hospital, without the auxiliary of professional equipment, by Inspection person's Self-operating, self-examination;Blood sampling volume is extremely low:Only need a drop finger tip blood, it is possible to while detecting Diagnostic Value of Several Serum Tumor Markers Index;High flux:Same capillary flow path, can once detect Diagnostic Value of Several Serum Tumor Markers;Tumor markers is in visible-range Read, without the optical device equipment such as exciting.

Claims (5)

1. a kind of tumor markers group detection micro-fluidic chip, it is characterised in that:Including substrate(1)And be positioned above Cover plate(2), the cover plate(2)For transparent material, the cover plate(2)On set blood sampling microneedle array(3), the blood sampling microneedle array (3)It is made up of multiple blood sampling micropins, there is micro-pipe the inside of every blood sampling micropin(14);The cover plate(2)And substrate(1)The two glue Close or thermocompression bonding forms spill cavity(4), sample cavity(16), reaction chamber(5), capillary flow path(8)With waste liquid chamber(15), it is described Sample cavity(16)And reaction chamber(5)Connected on vertical space, sample cavity(16)In upper, reaction chamber(5)Under;The sample cavity (16)Interior setting blotting paper(6)And filter paper(18);The reaction chamber(5)Positioned at filter paper(18)Lower section, the reaction chamber(5)It is built-in Micro-pillar array(7), reaction chamber(5)Bottom surface and micro-pillar array(7)Surface scribble the labelled antibody for being coupled chromophoric group;Institute State capillary flow path(8)Pass through time-delay valve(9)With reaction chamber(5)Connection;The capillary flow path(8)End edge region bottom The multiple test strips for being printed on immobilised antibody reagent are set(13)With quality control band(12), each test strip (13)For detecting a kind of tumor markers;The capillary flow path(8)Outside, with test strip(13)With quality control band (12)Standard detection colour band is printed at one-to-one position(10)Colour band is controlled with standard quality(11).
2. tumor markers group detection micro-fluidic chip according to claim 1, it is characterised in that:The blood sampling micropin Array(3)Made by the processing technology of microelectromechanical systems, built-in microchannel is connected with sample cavity.
3. tumor markers group detection micro-fluidic chip according to claim 1, it is characterised in that:
The blotting paper(6)With the micro-pipe in blood sampling micropin(14)Bottom it is closely coupled;The filter paper (18) is located at blotting paper (6) lower section, the top of reaction chamber (5).
4. tumor markers group detection micro-fluidic chip according to claim 1, it is characterised in that:The sample cavity (16) pass through overflow launder (17) between top and spill cavity (4) to connect.
5. tumor markers group detection micro-fluidic chip according to claim 1, it is characterised in that:The time-delay valve (9)For positioned at reaction chamber(5)And capillary flow path(8)Between one section long about 5 millimeters of capillary, its bottom surface has hydrophobic spy Property.
CN201720017398.9U 2017-01-07 2017-01-07 A kind of tumor markers group detection micro-fluidic chip Expired - Fee Related CN206420887U (en)

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Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN110824165A (en) * 2019-10-28 2020-02-21 江苏大学 Lung cancer tumor marker detection device and method based on micro-fluidic chip and mobile phone

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN110824165A (en) * 2019-10-28 2020-02-21 江苏大学 Lung cancer tumor marker detection device and method based on micro-fluidic chip and mobile phone
CN110824165B (en) * 2019-10-28 2022-12-16 江苏大学 Lung cancer tumor marker detection device and method based on micro-fluidic chip and mobile phone

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