CN1869700A - Sterility, infertility six-index integral investigating reaction plate and protein chip kit - Google Patents
Sterility, infertility six-index integral investigating reaction plate and protein chip kit Download PDFInfo
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- CN1869700A CN1869700A CN 200510102466 CN200510102466A CN1869700A CN 1869700 A CN1869700 A CN 1869700A CN 200510102466 CN200510102466 CN 200510102466 CN 200510102466 A CN200510102466 A CN 200510102466A CN 1869700 A CN1869700 A CN 1869700A
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Abstract
The invention relates to an integrated detection reaction orifice plate and protein chip reagent box for detecting six sterility indexes. And the reaction orifice plate comprises a substrate and reaction orifices on the substrate and the reaction orifices comprise 3-384 sample orifices, 1-300 negative contrast orifices, and 1-300 positive quality control orifices, where at the bottom of each reaction hole is solid carrier, coated with micro lattice of Sperm antigen (SAg), Zona pellucida antigen (ZPAg), Endometrium antigen (EMAg), Ovary antigen (OAg), Trophoblast antigen (TAg), and Human Chorionic Gonadotropin antigen (HCGAg) antigens or more. And the reaction orifice plate and reagent can simply and conveniently, rapidly and accurately implement simultaneously detection of six sterility indexes for many persons.
Description
Technical field
The invention belongs to external clinical examination and biochip technology field, exactly, it is a kind of sterility, infertility six index that is suitable for: sperm antibody (ASAb), anti-vitellary membrane antibody (AZP), AEA (EMAb), AOAb (AOA), anti-trophocyte's antibody (ATAb), the reaction plate and the kit of the integrated detection of anti-hCG antibodies (HCGAb).
Background technology
According to World Health Organization (WHO) prediction,, infertilely will become the third-largest disease that is only second to tumour and cardiovascular and cerebrovascular diseases in 21 century.Authority's data presentation, unwillingly the infertile incidence of property is 7%～46% in the married couple.Although different regions there are differences, generally be considered to 8%～15%.
Along with improving constantly of medical science applied development and detection means, immune infertility more and more is subject to people's attention, immune infertility that is since the autoimmunity or the isoimmunization of reproductive system antigen cause, be specific antigen as the cell that produces steroid hormone in sperm, refining, egg vitellary membrane and the ovary, cause that immune response produces corresponding antibodies, hinder sperm and combine with ovum and be fertilized and cause infertile.Wherein with sperm antibody cause infertile the most common.
Sperm is as a kind of antigen of uniqueness, and can cause self or homoimmune reaction after body immune system contacts, and produces AsAb (ASAb), infertile 10%～30% of the infertile patient that accounts for due to the AsAb.All may there be AsAb in men and women's body.Be present in serum or the refining at male anti-sperm antibody, then be present in serum or the cervical mucus in the women.AsAb and cervical mucus protein combination can disturb sperm to pass the cervical mucus onset of ovulation; The opsonic action of AsAb can promote the local phagocyte of genital tract engulfing sperm; The antibody of anti-sperm head can also be blocked smart ovum combination, causes the melting of embryonated egg of complement-mediated, and the infringement embryo implants and pre-embryo is grown and caused early abortion.
Oolemma (zona pellucid, ZP) be the acellular gelatin sample acidoglycoprotein film that one deck is holding egg mother cell and the preceding cytula of implantation, include the specificity sperm-receptor, in the process of bringing out sperm acrosome reaction, the identification of smart ovum, combination, penetrate and stop many inseminations, play an important role.Experimental study shows that oolemma antigen can stimulate of the same race or xenoantibody produces immune response, and oolemma has lost the binding ability with sperm of the same race after antiserum is handled; In vivo, vitellary membrane antibody can disturb the oolemma on cytula surface to come off and hinder implantation.Think that at present vitellary membrane antibody is one of reason of atocia.
Endometrium is embryo nidation and the ground that grows, but under pathological state, as endometritis, endometriosis and uterus adenomyosis etc., can change into antigen or haptens, stimulates body self to produce corresponding antibody.In addition, during induced abortion dilatation and curettage, blastular also may produce antibody as the antigenic stimulus body.In case have AEA to exist in women's body, just can cause infertile, stop pregnant or miscarry.
Owing to reasons such as ovary damage, infection, inflammation cause the excessive of ovary antigen, and cause AOAb AoA to produce, the high expressed of AOAb (AoA) is arranged among the infertile and miscarriage patient of about 42%-52%.Its AoA can further increase the weight of the damage of ovary, and causes the function of uterus, placenta unsound, causes infertile and miscarriage.
Human chorionic gonadotrophin (HCG) is a major hormone of keeping early pregnancy.But the women that history of spontaneous abortion, history of artificial abortion and biochemical pregnant history are arranged, in the miscarriage process, the HCG in the chorionic villi may produce antibody as the antigenic stimulus parent.Once accepted the HCG injection, to promote the women of ovulation, the anti-HCG antibody in the body also might be positive.This type of patient may show as infertile or habitual abortion clinically.In addition, in women's serum of unknown cause miscarriage, anti-trophocyte's antibody (ATAb) increases than normal pregnancies is obvious, this antibody increase and miscarry between close ties are arranged.Its mechanism may be relevant with the minimizing of blocking antibody.
At present, it is to use immuno-enzymatic mark (ELISA) indirect method that infertile serology detects, in can human body with infertile relevant above-mentioned antibody, these antibody are present in the interior or human body genital tract part of blood of human body, in refining, cervical mucus, but ELISA reagent can only detect single index at every turn, detects consuming time, consumption power, cost height, the clinical diagnosis market that is difficult to satisfy large sample carrying out many indexs.
High-tech technology-protein chip technology that occur recent years integrates efficient, accurate, inexpensive, easy and simple to handle, aspect the parallel fast detecting of many indexs incomparable advantage is being arranged.The present invention is by realizing the diagnosis to infertility to the fast detecting of six indexs, prediction and prognosis judgement have important directive significance to the prevention and the treatment of infertility.
Summary of the invention
Purpose of the present invention just provides a kind of sperm antibody (ASAb) that can detect simultaneously in serum or the blood plasma, anti-vitellary membrane antibody (AZP), AEA (EMAb), AOAb (AOA), anti-trophocyte's antibody (ATAb), anti-hCG antibodies (HCGAb) is totally six indexs, has the examination of infertility and the infertile diagnostic kit of detection dual-use function.
In a first aspect of the present invention, provide a kind of sterility, infertility six integrated detection reaction plate, the reaction orifice plate comprises substrate and the reacting hole that is positioned on the substrate, and described reacting hole comprises 3-384 sample aperture, 1-300 negative control hole, 1-300 positive quality control hole.Wherein, it is characterized in that: solid phase carrier is arranged at the bottom of each reacting hole, and bag is by sperm antigen (SAg) on solid phase carrier, oolemma antigen (ZPAg), endometrium antigen (EMAg), ovary antigen (OAg), trophocyte's antigen (TAg), human chorionic gonadotrophin antigen (HCGAg) microarray that antigen is formed more than six kinds or six kinds altogether is provided with a positioning reference point in each reacting hole.
In a preference, described solid phase carrier is NC film or PDVF film.
In another preference, the quantity of described sample aperture is 1-300.
In another preference, described sperm antigen (SAg), oolemma antigen (ZPAg), endometrium antigen (EMAg), ovary antigen (OAg), trophocyte's antigen (TAg), six kinds of antigens of human chorionic gonadotrophin antigen (HCGAg) respectively have 2-8 point of sample on solid phase carrier.
In another preference, the every hole of described reacting hole is provided with a positioning reference point.
In a second aspect of the present invention, provide a kind of sterility, infertility six integrated detection kit, it comprises the integrated detection reaction plate of the above-mentioned sterility, infertility six of the present invention.
In another preference, also comprise: enzyme mark working fluid, detection liquid, negative control, positive reference substance.
In another preference, described enzyme mark working fluid is made up of the anti-people's enzyme labelled antibody of rabbit, and described detection liquid is made up of shiner and two kinds of reagent of hydrogen peroxide, mixes before using.
In another preference, described shiner is luminol, different luminol or derivatives thereof.
Description of drawings
Fig. 1 is the point sample synoptic diagram of infertile related antigen on a kind of solid phase carrier of the present invention
Fig. 2 is each antigen that carries out in the reacting hole of the present invention---the synoptic diagram of antibody response
Embodiment
The key and the difficult point of the integrated detection of sterility, infertility six are, the sensitivity and the specificity that detect are directly connected to the result accurately and reliably, the present invention is extensive studies through going deep into, the detection reaction plate has been done improvement, use the microarray detection technique in the present invention, desmoenzyme immunity indirect method and chemiluminescence detection technology have improved the sensitivity and the specificity that detect greatly, thereby have solved the problems referred to above.
Particularly, for improving infertile associated antibodies more than six kinds and six kinds: sperm antibody (ASAb), anti-vitellary membrane antibody (AZP), AEA (EMAb), AOAb (AOA), anti-trophocyte's antibody (ATAb), anti-hCG antibodies (HCGAb), anticardiolipin antibody (ACA), the detection efficiency of blocking antibody (BA) etc., the present invention uses the microarray detection technique, desmoenzyme immunity indirect method and chemiluminescence detection technical design the integrated detection reaction plate of a kind of sterility, infertility six, the reaction orifice plate comprises substrate and the reacting hole that is positioned on the substrate, described reacting hole comprises 3-384 sample aperture, 1-300 negative control hole, 1-300 positive quality control hole, wherein, it is characterized in that: on the base plane of each reacting hole solid phase carrier is arranged, and bag is by sperm antigen (SAg) on solid phase carrier, oolemma antigen (ZPAg), endometrium antigen (EMAg), ovary antigen (OAg), trophocyte's antigen (TAg), the protein microarray of six kinds of antigens of human chorionic gonadotrophin antigen (HCGAg).
The quantity of each reacting hole is not particularly limited, and sample aperture is 3-384 usually, preferably 5-50.Negative control hole is 1-300, preferably 2-30.The positive quality control hole is for being 1-300, preferably 2-30.
In the present invention, the shape and the size of reacting hole are not particularly limited, and can be circular, square, sexangle, ellipse or other shapes.Size is generally diameter 0.1nm-8cm, and the degree of depth is 0.1nm-4cm.
In the present invention, the material of reaction plate substrate can be selected this area various materials commonly used for use, and preferable baseplate material comprises glass, plastics, pottery etc.
In the present invention, bag can be selected for use this area various solid phase carriers commonly used by the solid phase carrier of six kinds of antigens, and comprise (but being not limited to): glass sheet, plastics, cellulose nitrate (NC) film, PDVF film etc., preferable solid phase carrier comprises NC film, PDVF film.
On solid phase carrier, sperm antigen (SAg), oolemma antigen (ZPAg), endometrium antigen (EMAg), ovary antigen (OAg), trophocyte's antigen (TAg), six kinds of antigens of human chorionic gonadotrophin antigen (HCGAg) respectively have 2-8 point of sample, preferably 2-5 point of sample.In addition, preferably on solid phase carrier, also comprise an anchor point (see figure 1).Distance between each point of sample is generally 0.1nm-20mm.
On the other hand, the present invention also provides a kind of sterility, infertility six integrated detection protein chip kit, and this kit can be realized the parallelization of many indexs, microminiaturization, high throughput testing.It comprises reaction orifice plate of the present invention, cleansing solution, enzyme mark working fluid, detects liquid (A, B), negative control, positive quality control product etc.Wherein, enzyme mark working fluid liquid is made up of the anti-people's antibody of the rabbit of HRP mark, detects liquid and is made up of shiner and two kinds of reagent of hydrogen peroxide, and shiner is luminol, different luminol or derivatives thereof, mixes before using.
In the present invention, the detection of each index adopts enzyme to exempt from indirect method, detects principle as shown in Figure 2.Be described in detail as follows:
1) specific antigen is connected with solid phase carrier, forms solid phase antigen.Unconjugated site is removed in sealing.
2) add the serum of being examined of dilution: specific antibody wherein combines with antigen, forms the solid phase antigen antibody complex.Unconjugated antibody and impurity are removed in washing.
3) enzyme-added mark antiantibody with the antibodies in the solid-phase complex, thereby makes enzyme on this antibody indirect ground mark.After the washing, the enzyme amount on the solid phase carrier is just represented the amount of specific antibody.
4) add substrate: the substrate for enzymatic activity on the solid phase, chemiluminescence, CCD detects, and light intensity is represented the amount of being examined antibody in the sample
The present invention has fully utilized protein microarray detection technique dexterously, and enzyme immunity indirect method and chemiluminescence detection technology have realized that infertility detects index the time more than six kinds or six kinds.
Below in conjunction with specific embodiment, further set forth the present invention.Should be understood that these embodiment only to be used to the present invention is described and be not used in and limit the scope of the invention.The experimental technique of unreceipted actual conditions in the following example, usually according to normal condition, people such as Sambrook for example, molecular cloning: laboratory manual (New York:Cold Spring Harbor Laboratory Press, 1989) condition described in, or the condition of advising according to manufacturer.
Embodiment 1
The preparation of detection reaction plate
Get 96 orifice plates, 42-84 sample aperture is set, 1-8 negative control hole, 1-8 positive quality control hole.Place a solid phase carrier (NC film or PDVF film) in the bottom of each reacting hole, and bag is by sperm antigen (SAg) on solid phase carrier, oolemma antigen (ZPAg), endometrium antigen (EMAg), ovary antigen (OAg), trophocyte's antigen (TAg), the little array of protein (Fig. 1) of six kinds of antigens of human chorionic gonadotrophin antigen (HCGAg).
Embodiment 2
The kit preparation
Preparation contains the kit of the integrated detection of a sterility, infertility six index, and it contains one of the reaction orifice plate (8-200 person-portion) of embodiment 1,1 bottle of concentrated solution for washing, 1 bottle of enzyme mark working fluid detects one bottle of liquid A, detects one bottle of liquid B, one bottle of positive control, one bottle of negative control.
Concentrated solution for washing, enzyme mark working fluid, detection liquid A, detection liquid B
Embodiment 3
The integrated detection of sterility, infertility six index
By the following method each test blood please be detected by sample:
1. add diluted blood to be detected please or negative control, positive reference substance in the respective reaction hole, the 60-200ul/ hole.
2.30 ℃ of-42 ℃ insulation oscillating reactionss 30-60 minute.
3. with washing lotion washing 4-30 time, each 1-10 minute, vibration.
4. every hole enzyme-added mark working fluid 50-100ul.
5. with washing lotion washing 4-6 time, each 1-10 minute, vibration.
6. add and detect liquid 20-100ul/ hole, make and detect the bottom that liquid is uniformly distributed in the hole.
7, CCD detects, and looks luminous signal intensity exposure 3-15 second.
The result judges:
According to the CutOff value of different indexs,, judge the yin and yang attribute of sample serum with reference to negative control and positive quality control sky.
Meanwhile, with conventional method the blood serum sample of testing is carried out conventional sense.The result shows that the test result that draws with kit of the present invention is identical with conventional method.
All quote in this application as a reference at all documents that the present invention mentions, just quoted as a reference separately as each piece document.Should be understood that in addition those skilled in the art can make various changes or modifications the present invention after having read above-mentioned teachings of the present invention, these equivalent form of values fall within the appended claims of the application institute restricted portion equally.
Claims (9)
1. integrated detection reaction plate of sterility, infertility six, it is characterized in that, the reaction orifice plate comprises substrate and the reacting hole that is positioned on the substrate, described reacting hole comprises 3-384 sample aperture, 1-300 negative control hole, 1-300 positive quality control hole, wherein, it is characterized in that: solid phase carrier is arranged at the bottom of each reacting hole, and wraps on solid phase carrier by sperm antigen (SAg), oolemma antigen (ZPAg), endometrium antigen (EMAg), ovary antigen (OAg), trophocyte's antigen (TAg), the microarray of human chorionic gonadotrophin antigen (HCGAg) antigen more than six kinds or six kinds.In each reacting hole, also be provided with a location reference point.
2. reaction plate as claimed in claim 1 is characterized in that, described solid phase carrier is NC film or PDVF film.
3. reaction plate as claimed in claim 1 is characterized in that, the quantity of described sample aperture is 1-300.
4. reaction plate as claimed in claim 1, it is characterized in that, described sperm antigen (SAg), oolemma antigen (ZPAg), endometrium antigen (EMAg), ovary antigen (OAg), trophocyte's antigen (TAg), six kinds of antigens of human chorionic gonadotrophin antigen (HCGAg) respectively have 2-8 point of sample on solid phase carrier.
5. reaction plate as claimed in claim 1 is characterized in that, also is provided with a location reference point in each reacting hole.
6. the integrated detection protein chip kit of sterility, infertility six is characterized in that, it comprises the integrated detection reaction plate of the described sterility, infertility six of claim 1.
7. kit as claimed in claim 6 is characterized in that, also comprises: enzyme mark working fluid and detection liquid, negative control, positive reference substance.
8. kit as claimed in claim 7 is characterized in that, described enzyme mark working fluid is made up of the anti-people's antibody of the rabbit of HRP mark, and described detection liquid is made up of shiner and two kinds of reagent of hydrogen peroxide, mixes before using.
9. kit as claimed in claim 8 is characterized in that, described shiner is luminol, different luminol or derivatives thereof.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 200510102466 CN1869700A (en) | 2005-05-24 | 2005-09-14 | Sterility, infertility six-index integral investigating reaction plate and protein chip kit |
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN200510026129 | 2005-05-24 | ||
| CN200510026129.0 | 2005-05-24 | ||
| CN 200510102466 CN1869700A (en) | 2005-05-24 | 2005-09-14 | Sterility, infertility six-index integral investigating reaction plate and protein chip kit |
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| CN1869700A true CN1869700A (en) | 2006-11-29 |
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| CN 200510102466 Pending CN1869700A (en) | 2005-05-24 | 2005-09-14 | Sterility, infertility six-index integral investigating reaction plate and protein chip kit |
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Cited By (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102239410A (en) * | 2008-12-03 | 2011-11-09 | 霍夫曼-拉罗奇有限公司 | Test element having combined control and calibration zone |
| CN102262159A (en) * | 2010-05-27 | 2011-11-30 | 李建远 | Method for detecting 305 kinds of semen positioning protein of human testicle and epididymis expression related to procreation |
| CN103197057A (en) * | 2013-03-28 | 2013-07-10 | 天津市宝坻区人民医院 | Secreting type IgA endomethal antibody detection kit and use method of secreting type IgA endomethal antibody detection kit |
| CN104977400A (en) * | 2015-07-27 | 2015-10-14 | 三明市和众生物技术有限公司 | Infertility joint detection kit and detection method thereof |
| CN106932572A (en) * | 2017-04-26 | 2017-07-07 | 深圳市博卡生物技术有限公司 | For the kit and its detection method of infertile antibody test |
| CN112964882A (en) * | 2021-03-15 | 2021-06-15 | 深圳市新靶向生物科技有限公司 | Protein chip for detecting human body antimicrobial immunoglobulin and application thereof |
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2005
- 2005-09-14 CN CN 200510102466 patent/CN1869700A/en active Pending
Cited By (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102239410A (en) * | 2008-12-03 | 2011-11-09 | 霍夫曼-拉罗奇有限公司 | Test element having combined control and calibration zone |
| CN102239410B (en) * | 2008-12-03 | 2015-05-20 | 霍夫曼-拉罗奇有限公司 | Test element having combined control and calibration zone |
| CN102262159A (en) * | 2010-05-27 | 2011-11-30 | 李建远 | Method for detecting 305 kinds of semen positioning protein of human testicle and epididymis expression related to procreation |
| WO2011147274A1 (en) * | 2010-05-27 | 2011-12-01 | Li Jianyuan | Detection method for 305 fertility-associated sperm localization proteins expressed in human testis and epididymis |
| US9952224B2 (en) | 2010-05-27 | 2018-04-24 | Yantai Ju Jie Bioengineering Limited Company | Detection method for 305 fertility-associated sperm localization proteins expressed in human testis and epididymis |
| CN103197057A (en) * | 2013-03-28 | 2013-07-10 | 天津市宝坻区人民医院 | Secreting type IgA endomethal antibody detection kit and use method of secreting type IgA endomethal antibody detection kit |
| CN104977400A (en) * | 2015-07-27 | 2015-10-14 | 三明市和众生物技术有限公司 | Infertility joint detection kit and detection method thereof |
| CN106932572A (en) * | 2017-04-26 | 2017-07-07 | 深圳市博卡生物技术有限公司 | For the kit and its detection method of infertile antibody test |
| CN112964882A (en) * | 2021-03-15 | 2021-06-15 | 深圳市新靶向生物科技有限公司 | Protein chip for detecting human body antimicrobial immunoglobulin and application thereof |
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