CN1504579A - Microbe detecting cell chip - Google Patents

Microbe detecting cell chip Download PDF

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Publication number
CN1504579A
CN1504579A CNA02153831XA CN02153831A CN1504579A CN 1504579 A CN1504579 A CN 1504579A CN A02153831X A CNA02153831X A CN A02153831XA CN 02153831 A CN02153831 A CN 02153831A CN 1504579 A CN1504579 A CN 1504579A
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CN
China
Prior art keywords
corpse
microorganism detection
laboratory examination
chemical testing
cell chip
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Pending
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CNA02153831XA
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Chinese (zh)
Inventor
苏友欣
鲁希连
刘大章
龙训民
黄荣山
林世明
刘得杏
陈建勋
李世光
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GONGZHUN PRECISION INDUSTRY Co Ltd
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GONGZHUN PRECISION INDUSTRY Co Ltd
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Priority to CNA02153831XA priority Critical patent/CN1504579A/en
Publication of CN1504579A publication Critical patent/CN1504579A/en
Pending legal-status Critical Current

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  • Measuring Or Testing Involving Enzymes Or Micro-Organisms (AREA)

Abstract

A microbiological detection cell chip comprises an accommodating area corresponding the size of the detected member, the upper portion of the accommodating area is provided by an instilling port for letting in the detected body fluid, the lower portion is provided with a drawing port for extracting the non-detecting member, a deactivation layer covered on the surface of the accommodating area for repairing and inactivating the accommodating area and providing the background for the optical detection, and a detection layer embedding the passive surface by biological compatible polymer, making each detected member accurately positioned in a single accommodating area for the subsequent detection.

Description

The microorganism detection cell chip
Technical field
The present invention relates to a kind of microorganism detection cell chip, refer to a kind of localized biochip of the specific corpse or other object for laboratory examination and chemical testing of cell that is applied to detect especially.
Background technology
Biochip is that principles such as utilization molecular biology, gene information, analytical chemistry design, with silicon, glass or polymer organic plastics is support plate, cooperate high-tech element micro electronmechanical or that other precision processing technology is made, have be swift in response, the result accurately and bioanalysis detectability cheaply.In American-European advanced country, often utilize chip functions,, shorten the time-histories of new drug development to quicken life science.
The notion of biochip originated from for the 1980's, and biochip can be divided into gene chip (gene chip), program chip (process chip, lab-on chip) and protein chip (protein chip) according to its characteristic:
1. gene chip (gene chip): be on the support plate of area number square centimeter, settle thousands of made chips of gene section (being called nucleic acid probe) to tens thousand of Zhi Butong.During use chip placed tested liquid, make nucleic acid probe and the testing gene in the liquid on the chip hybridize (Hybridization), if certain fragment gene has hybridization, then can show different fluorescent looks, be able to be distinguished and look by naked eyes or specific apparatus.Its benefit is via one-time detection, and a large amount of various gene order relevant informations just can be provided, and exempts the time and effort consuming situation that in the past once can only detect a gene performance, significantly saves time and formality, to quickening to understand gene information very big benefiting is arranged.Most important and the most basic principle of gene chip is exactly to utilize the characteristic of hybridization that gene has, and reaches the purpose of identification gene.
2. protein chip (protein chip): with protein is bioprobe, and neat is arranged on the chip, carries out the Ag-Ab immune response, in order to detect protein.
3. program chip (process chip, lab-on chip): purpose is with Biochemical Lab's section experimental situation and equipment microminiaturization, in fact biochemical test is displaced on the chip and carries out, therefore in micro-fluid chip, utilize the many capillary channels of light shield etching, internal diameter of the pipeline is about hundreds of micron even about several microns, cooperate micro-electromechanical technology that testing liquid is pumped in the capillary channel again, make liquid in the environment that designs, separate (Separated), mix (Mixed), cultivate (Incubation), heating (Heated), the chain reaction of polymerized ferment PCR reactions identical such as (Polymerase Chain Reaction) with the laboratory.
In order synchronously parallel in a large number the cell or the gene that detect to be analyzed, many investigators rack one's brains invariably studies how to treat effectively that a corpse or other object for laboratory examination and chemical testing is positioned on the biochip, the most normal use no more than the microarray technology, this technology is to utilize mechanical arm in the high density arrays mode bioprobe to be fixed on the biochip, to treat that to extract pin a corpse or other object for laboratory examination and chemical testing contacts with bioprobe again, carry out check and analysis, yet each array point of this mode all need dispose physical prospecting pin and extraction pin throughout one's life, member is too complicated, and use the extraction pin to draw and treat a corpse or other object for laboratory examination and chemical testing, cause easily treating that a corpse or other object for laboratory examination and chemical testing and bioprobe damage.
Another kind of mode then is reaction zone that is provided with fixing biological probe and the fluid channel that cooperates sample solution to inject, detach, though sample and extraneous contacting can be effectively isolated in this kind configuration, reach good experiment control effect, and can not damage and treat a corpse or other object for laboratory examination and chemical testing, but consideration for fear of cost and technology, only can dispose several reaction zones on the biochip, be difficult to a large amount of detections, and may be adsorbed with a plurality of corpse or other object for laboratory examination and chemical testing by probe in the single reaction district, carry out follow-up fluorescent when detecting, because the activity and the biological nature of each corpse or other object for laboratory examination and chemical testing are all inequality, can influence the detection tolerance range.
Summary of the invention
Main purpose of the present invention is to solve above-mentioned defective, avoid the existence of defective, the present invention offers the disposal area according to specific corpse or other object for laboratory examination and chemical testing size on the microorganism detection chip, and outside the disposal area, be coated with passivation layer and detection layers, make each corpse or other object for laboratory examination and chemical testing be accurately positioned, can carry out subsequent detection in single disposal area.
Description of drawings
Relevant detailed description of the present invention and technology contents, existing conjunction with figs. is described as follows.
Fig. 1 is a manufacturing process synoptic diagram of the present invention.
Fig. 2-1 is a stereoscopic synoptic diagram of the present invention.
Fig. 2-2 is the local enlarged section synoptic diagram of Fig. 2-1.
Fig. 3 is the embodiments of the invention synoptic diagram.
Fig. 4 is the embodiments of the invention sectional schematic diagram.
Figure 5 shows that common corpse or other object for laboratory examination and chemical testing size.
Embodiment
Referring to Fig. 1,2-1,2-2, be manufacturing process of the present invention, stereoscopic and local enlarged section synoptic diagram.As shown in the figure: the manufacture method of aforementioned biochip may further comprise the steps: definition corpse or other object for laboratory examination and chemical testing accommodation space 1, be that the length and width that cuts at Silicon Wafer respectively is on 2 centimetres of chips, with crystal round etching and arrayed mode (each 100 point of length and width, totally one ten thousand points) corpse or other object for laboratory examination and chemical testing that limits downward gradually-reducing shape on microorganism detection chip 10 is kept somewhere the space, this accommodation space top is one to splash into mouthfuls 11, aforesaid etching technique can be wet etching or dry etching, wet etching is to carry out etching with chemical reaction, and dry etching then utilizes physical action to carry out.
After finish in corpse or other object for laboratory examination and chemical testing indwelling space, cut a non-corpse or other object for laboratory examination and chemical testing and detach mouth 2, big or small cutting is kept somewhere bottom the space according to a specific corpse or other object for laboratory examination and chemical testing, and bottom, feasible indwelling space forms one and detaches mouth 12, splashes into mouth 11 and detaches the disposal area 13 that mouth 12 limits the downward convergent of a wall by aforementioned.
Coat passivation layer 3, after finishing disposal area 13, for further accurately controlling the size of disposal area 13, form a passivation layer 14 on 13 surfaces, aforementioned disposal area, this passivation layer 14 forms for chromium metal is plated on 13 surfaces, disposal area, this passivation layer 14 has two effects: (one) can repair the sharp-pointed contact angle in aforementioned disposal area 13 by this metal passivation layer 14, and further accurately control detach mouthfuls 12 aperture; (2) when the detection thing carries out the fluorescent detection, background had better not produce the light reflection, detect numerical value and influence scanner CCD (charge-coupled device) or confocal laser scanning (confocal laser scanning), ideal state is black array (black matrix), by the light absorptive of chromium, reduce the optical detection error.
After finishing passivation layer, exert an influence and cause detecting error for fear of 14 pairs of corpse or other object for laboratory examination and chemical testing of passivation layer, coating detection layers 4, this detection layers 15 is that deposition one biological compatible polymer forms on passivation layer 14 surfaces, this biocompatible polymer is poly-terephthaldehyde's alkene (Parylene, poly-p-xylylene) generating with depositional mode after the process of overflash (150 ℃) and cracking (650 ℃), the advantage of poly-terephthaldehyde's alkene is that drape is good, can completely cut off below passivation layer 14 fully.
Referring to Fig. 3,4, be the embodiments of the invention synoptic diagram.As shown in the figure: this microorganism detection chip 10 can be assembled on the pedestal 20 and use, this pedestal 20 comprises for the ccontaining positioning area 21 of microorganism detection chip 10 and is positioned at these positioning area 21 belows and both sides are connected to the pump (not shown) detaches passage 22, during use, microorganism detection chip 10 is placed in the positioning area 21 of pedestal 20, and the passage 22 that detaches of pedestal 20 is connected to pump respectively, promptly finish the detection system configuration this moment.When experimentizing, sample solution is advanced aforementioned micro organism detection chip 10 by splashing into 11 in mouth, restarting pump detaches impurity in the sample solution and moisture in mouth 12 and detaches passage 22 extractions by the below, simultaneously, because pump provides a pressure difference, make a corpse or other object for laboratory examination and chemical testing more strong fix in the disposal area 13 of microorganism detection chip 10 (referring to Fig. 2), close pump, then each corpse or other object for laboratory examination and chemical testing is located in respectively in each disposal area 13, can carry out subsequent detection.
Because disposal area 13 of the present invention, therefore detaches the aperture of mouth 12 in order to the corpse or other object for laboratory examination and chemical testing of location specific dimensions and must be provided with at corpse or other object for laboratory examination and chemical testing size, the size of a common corpse or other object for laboratory examination and chemical testing sees for details shown in Figure 5.A most frequently used corpse or other object for laboratory examination and chemical testing with the human body disease comprises: liver cell, red blood corpuscle and bacterium, its size is between 100nm-10 μ m (micron-scale), therefore, as desire to detect at this kind cell, mouthful 12 pore sizes of detaching then of the present invention must be less than 100nm, as detecting the corpse or other object for laboratory examination and chemical testing of bigger (vegetable cell) or littler (nano-scales such as virus, protein or DNA), only need change to detach the pore size of mouth 12, a specific corpse or other object for laboratory examination and chemical testing can be positioned in the disposal area 13, as for size littler impurity or water, then can detach mouth 12 and be isolated by 13 belows, disposal area.

Claims (15)

1. a microorganism detection cell chip is characterized in that, this microorganism detection cell chip includes:
One disposal area, corresponding each corpse or other object for laboratory examination and chemical testing size of its accommodation space is provided with, and this top, disposal area is provided with for what corpse or other object for laboratory examination and chemical testing liquid entered and splashes into mouth, and the below is provided with the mouth that detaches that a non-genus corpse or other object for laboratory examination and chemical testing isolates;
One passivation layer is coated in surface, aforementioned disposal area, in order to repair the aforementioned disposal area of passivation and the background of optical detection is provided; And
One detection layers is to be coated on aforementioned passivation layer surface with biocompatible polymer to form.
2. microorganism detection cell chip according to claim 1 is characterized in that, this microorganism detection cell chip can be each chip of 2 centimetres of length and width.
3. microorganism detection cell chip according to claim 2 is characterized in that, the respectively above array way setting above 5 of length and width is adopted in this disposal area on the microorganism detection cell chip.
4. microorganism detection cell chip according to claim 1, this disposal area splash into oral pore footpath greater than detaching mouth, make the wall of disposal area become a downward gradually-reducing shape.
5. microorganism detection cell chip according to claim 1, it is characterized in that this passivation layer is made by chromium metal or chromated oxide, can repair the sharp-pointed contact angle in passivation disposal area, and, provide the background of optical detection by chromium or chromated oxide low reflectivity to light.
6. microorganism detection cell chip according to claim 1, it is characterized in that, the polymer layer of this biocompatibility as poly-terephthaldehyde's alkene (Parylene, poly-p-xylylene) etc., make when this chip contacts with a corpse or other object for laboratory examination and chemical testing the unlikely activity that influences a corpse or other object for laboratory examination and chemical testing.
7. microorganism detection cell chip according to claim 1, it is characterized in that, this microorganism detection cell chip can be assembled on the pedestal and use, and this pedestal comprises for the ccontaining positioning area of microorganism detection chip and is positioned at this positioning area below and both sides are connected to the passage that detaches of pump.
8. microorganism detection cell chip according to claim 1 is characterized in that, this detaches the size of the direct corresponding corpse or other object for laboratory examination and chemical testing in aperture of mouth, and this aperture that detaches mouth is slightly less than a corpse or other object for laboratory examination and chemical testing.
9. microorganism detection cell chip according to claim 1 is characterized in that, the big I of a corpse or other object for laboratory examination and chemical testing is divided between centimetre, micron and time micron: vegetable cell, zooblast, general blood cell and bacterium.
10. the manufacture method of microorganism detection cell chip according to claim 1 is characterized in that, this manufacture method may further comprise the steps:
A) limit corpse or other object for laboratory examination and chemical testing accommodation space, form the corpse or other object for laboratory examination and chemical testing accommodation space of downward gradually-reducing shape according to corpse or other object for laboratory examination and chemical testing size in the crystal round etching mode on the microorganism detection chip, this accommodation space top is one to splash into mouth;
B) the non-corpse or other object for laboratory examination and chemical testing of cutting detaches mouth, according to the aforementioned accommodation space of specific corpse or other object for laboratory examination and chemical testing size cutting bottom, makes this accommodation space bottom form one and detaches mouth for what a non-corpse or other object for laboratory examination and chemical testing was isolated, splashes into mouthful and detach the disposal area that mouth limits the downward convergent of a wall by aforementioned;
C) coat passivation layer,, form a passivation layer on surface, aforementioned disposal area for accurately controlling the disposal area size; And
D) coating detection layers avoids the activity of a corpse or other object for laboratory examination and chemical testing to be affected, and is formed with a biological compatible polymer layer in aforementioned passivation layer surface.
11. the manufacture method of microorganism detection cell chip according to claim 10 is characterized in that, this microorganism detection cell chip can be each chip more than 0.2 centimetre of length and width.
12. the manufacture method of microorganism detection cell chip according to claim 10 is characterized in that, this accommodation space respectively surpasses 5 above array way configurations with length and width on the microorganism detection chip.
13. the manufacture method of microorganism detection cell chip according to claim 10 is characterized in that, this crystal round etching can be wet etching or dry etching.
14. the manufacture method of microorganism detection cell chip according to claim 10, it is characterized in that, this passivation layer can be plated on the surface, disposal area by chromium metal, can repair the sharp-pointed contact angle in passivation disposal area, and, provide the background of optical detection by chromium or chromated oxide low reflectivity to light.
15. the manufacture method of microorganism detection cell chip according to claim 10, it is characterized in that, this detection layers is poly-terephthaldehyde's alkene (Parylene, poly-p-xylylene) be formed at passivation layer surface with depositional mode, make when this chip contacts with a corpse or other object for laboratory examination and chemical testing the unlikely activity that influences a corpse or other object for laboratory examination and chemical testing.
CNA02153831XA 2002-11-28 2002-11-28 Microbe detecting cell chip Pending CN1504579A (en)

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Application Number Priority Date Filing Date Title
CNA02153831XA CN1504579A (en) 2002-11-28 2002-11-28 Microbe detecting cell chip

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CN1504579A true CN1504579A (en) 2004-06-16

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Cited By (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2005059553A1 (en) * 2003-12-19 2005-06-30 Chengdu Kuachang Medical Industrial Limited The biochip assay and its relative equipment
CN101550396B (en) * 2009-05-08 2011-11-23 深圳先进技术研究院 High-throughput microfluidic cell chip
CN103981082A (en) * 2014-06-04 2014-08-13 天津禄浩科技有限公司 Cell amyloidosis detection chip and reagent thereof
WO2024152158A1 (en) * 2023-01-16 2024-07-25 王锦弘 Biochip manufacturing method and product thereof, and testing method using biochip

Cited By (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2005059553A1 (en) * 2003-12-19 2005-06-30 Chengdu Kuachang Medical Industrial Limited The biochip assay and its relative equipment
CN101550396B (en) * 2009-05-08 2011-11-23 深圳先进技术研究院 High-throughput microfluidic cell chip
CN103981082A (en) * 2014-06-04 2014-08-13 天津禄浩科技有限公司 Cell amyloidosis detection chip and reagent thereof
WO2024152158A1 (en) * 2023-01-16 2024-07-25 王锦弘 Biochip manufacturing method and product thereof, and testing method using biochip

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