CN1657945A - Sample dripping instrument for preparing tissue chip - Google Patents
Sample dripping instrument for preparing tissue chip Download PDFInfo
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- CN1657945A CN1657945A CN 200410016404 CN200410016404A CN1657945A CN 1657945 A CN1657945 A CN 1657945A CN 200410016404 CN200410016404 CN 200410016404 CN 200410016404 A CN200410016404 A CN 200410016404A CN 1657945 A CN1657945 A CN 1657945A
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- point sample
- organization chip
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Abstract
This invention relates to a high density organization chip making equipments, concretely is in the high density organization chip manufacture core equipments- high density chip type meter design and the manufacture, and with its preparation high density organization chip core technology, selects the type meter including the bracket fixing, the adjusting clamp, and supplies the acupuncture and recieved the acupuncture, the positioning device and so on. This equipment unique design had guaranteed the sample and the type accuracy, enhanced the type speed and the chip density.
Description
Technical field
The invention belongs to high density organization chip manufacture technology field, especially the technology of preparing of high density organization chip point sample instrument.
Background technology
The diagnosis of disease is all closely related with histiocytic gene and the variation of relevant molecule thereof with treatment, and this molecule variation just has clinical value when being ubiquitous.In fact, the evaluation for a molecular marker needs hundreds of tissue specimens to thousands of different stages of development.Yet traditional pathology method and be based upon immunohistochemistry on its basis, the tissue specimen that in situ hybridization and original position PCR etc. is detected in most of the cases all is single, that be dispersed in, accidental, isolated.If carry out correct evaluation to a molecular marker then needs expensive human and material resources and financial resources, and be a very very long and complicated process.In order to solve this difficult problem, many scientists have carried out a large amount of research.The Kononen of the NIH of NIH in 1998 (Kononen J, Bubendorf L etc., " being used for little detection of organizing of tumor sample high flux characterization of molecules " (Tissue microarrays for high-throughputmolecular profiling of tumor specimens), Nat Med., in July, 1998; 4 (7): 844-7) reported a kind of tissue Microarray technology, and become the new focus of biochip research field.Use this technology, (Schraml P such as Schraml, Kononen J, Bubendorf L etc., " be used for many different tumor types gene magnification research organize little detection " (Tissue microarrays for gene amplification surveys in many differenttumor types), Clin Cancer Res, 1999; 5 (5): 1966-1975) in a week, detected the expression of CCND1, CMYC and three kinds of oncogenes of ERBB2 in 17 kinds of tumour 397 routine tissue samples; (RichterJ such as Richter, Wagner U, Kononen J etc., " the little check and analysis of the high-flux tissue of cyclin E gene magnification and overexpression in the carcinoma of urinary bladder " (High-throughout tissue microarray analysis ofcyclin E gene amplification andoverexprssion in urinary bladder cancer), Am Society Invest Pathol, 2000,157 (3): 787-794) in two weeks, detected the expression of cyclin E gene and the CCNE in this of 2317 increments in the 1842 routine bladder cancer patients.Obviously, this method has improved the efficient that detects greatly, has quickened progress of research, has shortened the cycle of studying, has also saved reasearch funds simultaneously.
Tissue array technology is that a large amount of tissue specimens are integrated and be fixed on the slide of special processing and hybridize with the sample molecule of mark then, the hybridization signal intensity by detecting each probe molecule and then obtain the information of sample molecule quantity, distribution, expression in particular organization.The preparation of organization chip needs various various disease tissues and relevant clinical data and pathological data, and the development of technology is subjected to resource limit bigger, so than biochip technologies such as DNA chip, protein chip, slower development.But DNA chip and tissue array technology are complementary.The effect of DNA chip can be summarized as the height intensification that makes biological information, as detecting the expression situation of thousands of kinds of genes in a tumor tissues, and the effect of organization chip can be summarized as the height amplificationization that makes biological information, as detecting a kind of or one group of expression of gene situation in nearly thousand kinds of tumours.This detection can be finished on a slide, its high efficiency, and scientific and economy is that classic method is incomparable.
Since tissue array technology was born in 1998, domestic and international in recent years many pieces of patents and article all had report, and technology is constantly progressive, and novel chip continues to bring out.
The technical scheme that existing tissue array technology is mainly taked is: employing mechanization apparatus for preparation or automated preparation instrument take out cylindric tissue core from donor paraffin organization sample (tissue-derived in various malignant tumours, various benign tumours, various cancer premutations, various non-neoplastic diseases, various normal structures, various embryonic tissues, various blood and hematopoietic tissue, each total cell extract, various biopsies or cell, various hydrothorax, ascites, sputum, cell in the transudate, the histocyte of various in vitro culture and clone, various bacteriums and saccharomycete, various transgenic animals tissues or various transgenosis organs etc.), each cylindric tissue core is placed in the blank wax stone of another piece (acceptor piece) by design sequence, formative tissue microarray wax stone, from this micro-array tissue wax stone, can obtain a large amount of micro-array tissue sections, section being placed on the slide of silication and gel is the formative tissue micro-array biochip, comprises a large amount of orderly various donor paraffin organization samples on each tissue microarray biochip.
The technical development of mechanization organization chip point sample is to today, and existing many companies such as ALPHELYS, CHEMICON, Genxpress, Alpha Metrix etc. develop multiple different point sample instrument.Technology such as we take the lead in adopting 96 orifice plate point sample methods on the basis of these point sample instrument relative merits of research, make groove at the magnetic fixed pan and carry out sample and fix, and locating device is preposition have improved speed, the accuracy of point sample, have very high use value.
Summary of the invention
The present invention relates to a kind of organization chip point sample instrument, this point sample instrument comprises fixed mount 10, fixed head 3, stationary installation 1, container 2, decompressor 5, positioning disk 6, location-plate 7, punching press base 8, is subjected to body acupuncture 11 and devices such as donor pin 12, horizontal gauge 4, vertical gauge 13, wherein, this stationary installation 1 is slightly larger than described container 2, and has groove on it.
The invention still further relates to a kind of organization chip point sample instrument, this point sample instrument comprises fixed mount 10, fixed head 3, stationary installation 1, container 2, decompressor 5, positioning disk 6, location-plate 7, punching press base 8, is subjected to body acupuncture 11 and devices such as donor pin 12, horizontal gauge 4, vertical gauge 13, wherein, described horizontal gauge 4 is operated thereby help the technician by preposition.
The invention still further relates to a kind of organization chip point sample instrument, this point sample instrument comprises fixed mount 10, fixed head 3, stationary installation 1, container 2, decompressor 5, positioning disk 6, location-plate 7, punching press base 8, is subjected to body acupuncture 11 and devices such as donor pin 12, horizontal gauge 4, vertical gauge 13, wherein, described stationary installation 1 is slightly larger than described container 2, and have groove on it, described horizontal gauge 4 is by preposition.
The invention still further relates to and adopt organization chip point sample instrument of the present invention to make 96 orifice plates, and carry out 96 orifice plate point samples.
Description of drawings
Fig. 1 is the synoptic diagram of the preferred organization chip point sample instrument of the present invention.
Fig. 2 is an organization chip spotting needle synoptic diagram.
Fig. 3 is an organization chip point sample instrument location-plate synoptic diagram.
Embodiment
Below in conjunction with accompanying drawing the present invention is explained in detail.The present invention is not subjected to the restriction of these embodiments, and any modification that does not depart from spirit of the present invention and change are all within protection scope of the present invention.
Fig. 1 shows the synoptic diagram of the preferred organization chip point sample instrument of the present invention.Among the figure, stationary installation 1, fixed head 3 on fixed mount 10, have been placed.Stationary installation 1 is top reeded magnetic stationary platform, and its preposition horizontal gauge 4 of ining succession has been placed container 2 on it.The groove of stationary installation 1 can randomly be various suitable shapes, for example is square, circular or the like.The width of groove is about 3-10mm, generally is about 5mm.The degree of depth of groove is about 3-5mm, is about 3mm usually.Relative position between each groove does not limit, but the distance that is preferably between each groove is identical.Distance between its adjacent limit of adjacent groove be there is no concrete restriction, and still, this distance generally is about 3-10mm, is generally about 5mm.Compare with traditional device, on stationary installation, draw the use amount of the fluted material that deperms, thereby magnetic force is reduced, when guaranteeing fixed mass, be more convenient for moving and picking and placeing container 2.In addition, sampling point sample operation is not affected yet, on the contrary because picking and placeing of container 2 is more easy to operate, its laying more accurate and improved the accuracy of point sample and sampling greatly on this stationary installation 1.The auxiliary positioning effect is also played to container 2 in the position of groove cylindrical void.
Among Fig. 1, horizontal gauge 4 is by preposition.Preposition horizontal gauge 4 brings great convenience also for technician's implementation and operation, no longer needs an arm to walk around whole instrument during as positioning action and positions operation from the back side, and positioning action is simpler, has also reduced the pollution to sample; Simultaneously, preposition after with the naked eye detection receptacle 2 locate whether there is skew in sampling with during point sample, improved speed, the accuracy of point sample.
The donor piece is placed in the position of container 2.Decompressor 5 is installed on the fixed head 3, comprise one vertically upward positioning disk 6 and the location-plate 7 on the horizontal direction, location-plate 7 is installed on the horizontal gauge 4, can carry out the measurement and the adjusting of micron level accurately like this.Vertically-guided dish 6 provides accurate guide surface, and punching press base 8 can slide along flexible track in the plane.Flexible track assists punching press base 8 to reset along track by elastoplast, be installed on the base 8 by body acupuncture 11 and donor pin 12, can stretch out or withdraw to container 2 along dull and stereotyped 3, regulated by the precession and the back-out of vertical gauge 13 by the motion amplitude of body acupuncture 11 and donor pin 12, endoporus is extended down on the base 8, and opening is positioned on the lip shape edge 9.
Usually, the needed material of preparation organization chip has:
(1) paraffin embedded tissues that comprises different focuses of humans and animals all sites and different development stage of routine pathology method preparation or cell wax stone (being called for short the donor piece), all donor tissue samples that wherein derive from people or other animals are all with corresponding clinical information, comprise age, sex, clinical symptoms, diseased region and pathological diagnosis result comprise tumour or other diseases by stages, classification, differentiation, origin of cell, types of organization and immunohistochemical staining result thereof etc.;
(2) be used to accept the small cylindric tissue that obtains from the donor piece or the blank wax stone (being called for short the acceptor piece) of cell;
(3) be used to diagnose and locate hematoxylin-eosin (HE) stained that derives from same donor piece;
(4) common slide and the silication slide of handling with particular adhesive, corresponding cover glass and mounting glue;
(5) adhesive tape of special processing;
(6) come unstuck accordingly and dewaxing agent;
(7) point sample instrument.
Histotomy through HE dyeing or additive method dyeing can obtain from the donor piece, and be placed on the slide, diagnose and the mark of different colours is carried out at needed diseased region or other positions that will study, represent cancerous tissue, blue colour specification cancer beside organism, yellow expression metastases tissue, the green normal structure or the like of representing as black.The jib 26 of slide with articulation structure grasps and places on the donor as shown in Figure 3, clamp 24 on the jib 26 is grasping the edge of transparent microslide 23, jib 24 can change angle in 25 places in the joint, primary importance is fixed in microslide 23 on the container 2, and the second place is removed to appear the donor pin microslide 23 horizontal directions.In conjunction with Fig. 1, concrete operations are as follows: container 2 is placed on the platform 1 and makes container 2 be fixed on appointed positions, organizing in the donor piece is fixed in through the conventional section of paraffin embedding (3 μ m-5 μ m) and with sample and carried out HE dyeing on the slide, be positioned over then on the microslide 23, and be positioned on the donor piece, slide can move on microslide 23, tissue sample 15 in sample 16 and donor piece overlaps fully, jib 26 is fixed in primary importance, by the selected diseased region 17 (as when tissue sample is breast cancer; diseased region 17 is exactly the tissue with breast cancer characteristic structure) of pathological diagnosis institute mark, the donor piece below it has the tissue specimen of same structure to be positioned simultaneously.As shown in Figure 4, location-plate 1 can move at the X-Y direction of principal axis under milscale and control lever control.With donor at tissue site selected in the donor piece, remove microslide 23, the donor stylus printer is gone into tissue site selected in the donor piece, decompressor 5 moves down until dull and stereotyped 7 along track, the donor pin takes the tissue in the piece of tissue downwards, can obtain tissue sample behind the retraction, stretch into opening with probe and can obtain columniform tissue sample.Put it in shape and the big or small identical acceptor piece, the acceptor piece can be prepared before sampling, and method of operating is that blank wax stone is placed in the container 2, goes out cylindrical hole with the acceptor stylus printer, the array in hole is with arranging of designing, and wherein preferred 96 orifice plate samples design.Adopt 96 orifice plates, can adapt, once give a plurality of holes application of sample, thereby improved efficient greatly with the volley of rifle fire of present use.
The method that obtains conventional blank array wax stone arrangement is: at first will be subjected to body acupuncture to be placed on reference position (as the blank wax stone upper left corner), with acceptor stylus printer hole, move decompressor or acceptor piece at the X-Y direction of principal axis again, repeat above step, just can be made into blank array (for example 96 orifice plates) wax stones (acceptor piece) of different matrixes.Blank acceptor piece aperture among Fig. 3 is 0.6mm, and the centre distance of Kong Yukong is 0.7mm, and the adjacent holes distance is 0.1mm.During sampling, in the ordinary course of things, it is 2-6mm highly that cylindrical tissue takes, and radius is 0.3-1.0mm.Mark region sampling from the donor piece, and arrange to new blank acceptor piece, the sampling radius can be regulated arbitrarily between 0.1-2.0mm, the radius of taking a sample generally speaking is comparatively suitable between 0.3-1.0mm, not only can be unlikely to simultaneously the institutional framework in the former donor piece is caused damage for the usefulness of analysis.
Put excellent paraffin embedded tissues and put into 37 ℃ of incubators 15 minutes, to increase the stickiness between cylindrical tissue samples and the blank wax stone and the pliability of tissue micro-array wax stone, and make its smooth surface smooth, cover with adhesive film again, after adhesive film places, cut the thick micro-array tissue section of 4-8 μ m along total direction of principal axis, be positioned on the slide (needing to use the particular adhesive treatment surface), remove adhesive film after smooth, an end of slide is used for identification and label orientation.
Point sample, the acceptor piece after hatching through cut into slices, fix, come unstuck, dewaxing and HE dye or other dyeing, is used for various biological study, qualitative and medical diagnosis etc.
Claims (7)
1. organization chip point sample instrument, this point sample instrument comprises fixed mount (10), fixed head (3), stationary installation (1), container (2), decompressor (5), positioning disk (6), location-plate (7), punching press base (8), is subjected to body acupuncture (11) and donor pin (12), horizontal gauge (4), vertical gauge (13), it is characterized in that, the distance on four limits of four limits of described stationary installation (1) and described container (2) is 1-5cm, and this stationary installation has groove on (1).
2. organization chip point sample instrument as claimed in claim 1 is characterized in that, described horizontal gauge (4) is by preposition.
3. organization chip point sample instrument as claimed in claim 1 is characterized in that, described distance is 1-3cm.
4. organization chip point sample instrument as claimed in claim 3 is characterized in that, described distance is 2cm.
5. organization chip point sample instrument as claimed in claim 1 is characterized in that, the wide 3-10mm of described groove, dark 3-5mm.
6. organization chip point sample instrument, this point sample instrument comprises fixed mount (10), fixed head (3), stationary installation (1), container (2), decompressor (5), positioning disk (6), location-plate (7), punching press base (8), is subjected to body acupuncture (11) and donor pin (12), horizontal gauge (4), vertical gauge (13), it is characterized in that described horizontal gauge (4) is by preposition.
7. the purposes of claim 1 or 6 described organization chip point sample instruments is characterized in that, is used to prepare 96 orifice plate sample chips.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 200410016404 CN1657945A (en) | 2004-02-18 | 2004-02-18 | Sample dripping instrument for preparing tissue chip |
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 200410016404 CN1657945A (en) | 2004-02-18 | 2004-02-18 | Sample dripping instrument for preparing tissue chip |
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| CN1657945A true CN1657945A (en) | 2005-08-24 |
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103406164A (en) * | 2013-07-15 | 2013-11-27 | 广东凯普生物科技股份有限公司 | Removable film-loading platform with magnetic force |
| CN111426532A (en) * | 2020-04-09 | 2020-07-17 | 北京大学深圳医院 | Bacterial wax block preparation method and method for positive quality control of bacterial wax block as acid-fast staining |
-
2004
- 2004-02-18 CN CN 200410016404 patent/CN1657945A/en active Pending
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103406164A (en) * | 2013-07-15 | 2013-11-27 | 广东凯普生物科技股份有限公司 | Removable film-loading platform with magnetic force |
| CN103406164B (en) * | 2013-07-15 | 2015-04-01 | 广东凯普生物科技股份有限公司 | Removable film-loading platform with magnetic force |
| CN111426532A (en) * | 2020-04-09 | 2020-07-17 | 北京大学深圳医院 | Bacterial wax block preparation method and method for positive quality control of bacterial wax block as acid-fast staining |
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Owner name: SHANGHAI CHENJIAN ANTIBODY GROUP PHARM GMBH Free format text: FORMER OWNER: SHANGHAI FUCHUN ZHONGNAN BIOTECHNOLOGY CO., LTD. Effective date: 20060901 |
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Effective date of registration: 20060901 Address after: 201203 Shanghai Guo Shou Jing Road, Zhangjiang hi tech Park 351 Building No. 2 room 694-18 Applicant after: Shanghai morning strengthening antibody group medicine Co Ltd Address before: 201203, room 1011, 501 Harley Road, Zhangjiang hi tech park, Shanghai Applicant before: Shanghai Fuchun Zhongnan Biotechnology Co., Ltd. |
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