CN2718580Y - Crimped folding compound micro-array chip bar - Google Patents

Abstract

The utility model provides a crimped folding compound micro-array chip bar, belonging to the technical field of the biochemistry analysis. The gene chip microorganism device can be crimped into a crimped compound micro-array rod according to the method of the crimped folding compound micro-array, and the crimped compound micro-array rod comprises multi-hole rods and a sticking film. The multi-hole rod can be crimped by a thin film, and also can use directly the ready multi-hole micro-rod. A compound is attached and fixed on each multi-hole rod through the chemical method, and the multi-hole rods are stuck on the sticking film according to the scheduled arranging regularity. The film stuck with the multi-hole rods can be crimped and folded into the rod shape and can comprise an array chip rod with the multi-hole rods, the array chip rod with the multi-hole rods can proceed cutting into slices, and each slice can be a compound micro-array chip. The utility model releases completely the mask manufacturing process and the repeated positioning process with high price and trouble manufacture in the process of the existing biochip preparation, has the advantages of simple operation, less equipment investment, easy automatic control, and the high coupling efficiency can be ensured. Meanwhile, the fillers can not be arranged between the array points of the utility model, without the background signal disturbing, and the utility model can be used for various analysis methods.

Description

A kind of collapsible micro-array chip of chemical compound rod that curls

Technical field

The utility model relates to a kind of usefulness to be provided thin layer method or with the microorganism device of multi-level tray, also relates to a kind of compound micro array apparatus simultaneously, and especially a kind of biomacromolecule microarray belongs to the biochemical analysis technical field.

Background technology

Biochip has extremely important meaning on biological detection, medical test and medical diagnosis on disease, drug screening and gene sequencing.Traditional biological detects the method adopted and comprises a series of numerous and diverse steps, especially extensive biologic artifact detect and screening aspect time-consuming, effort, cost height, can not satisfy the demand.For example, porous check-out console (as 96 orifice plates) is the existing a kind of conventional utensil that is used for medicine, biochemistry detection and screening that generally uses.Its basic skills is respectively different proteins, nucleic acid probe, cell line or biological tissue to be placed or be fixed among the different holes, by adding different chemicals, or compound combination, or biochemical reagents, or detected biological sample, observe the reaction of different chemical/biological substance, carry out fast parallel biochemical analysis, clinical examination or drug screening.96 reaction tanks on it are isolated from each other, and can select the number of reaction tank arbitrarily for use according to user's needs.As a kind of method of generally using in existing Biochemical Research and the exploitation,, make in the research process that compound is synthetic or buy to require a great deal of time and expense because research object compound number is huge.The ordered arrangement of sample also will spend a large amount of time simultaneously.

Classic method is being carried out in the improved process, and biochip technology arises at the historic moment.The strong means that provide are obtained and analyzed to the maturation of this technology and use and will bring a revolution for the early stage fast detecting and the life science association areas such as new drug development, food inspection and environmental monitoring of disease for biological information.

The genetic chip technology of preparing can be divided into point sample method and in-situ synthesis.So-called point sample method, dna probe or the cDNA probe stationary of promptly using the whole bag of tricks (printing, spray printing, point sample) to synthesize in advance form microprobe array on slide or other solid slide glass.Original position is synthetic then to be directly probe to be synthesized on substrate according to the base sequence that designs in advance.The point sample method is suitable for the preparation of low density gene chip, high slightly number of probes (for example promptly needs very high cost, when 20 purpose number of probes reach 1000, the probe cost is promptly 300, about 000 yuan), thereby work as number of probes more for a long time, this technology can't be thought analogy with the original position synthetic technology, also has various objective factors to cause the inhomogeneous thereby uneven shortcoming of hybridization signal of probe density in addition.From the angle of large-scale mass production and application prospect from now on, reliable quality high-density gene chip mass technology of preparing is important development trend, even the more low-density genetic chip of exploitation is badly in need of in clinical diagnosis, because the product quality of the synthetic preparation of original position is more stablized parallel reliable, also superior than the point sample method, thereby have demand and market outlook widely.At present in the world; developed multiple DNA array original position synthetic technology; but because such-and-such deficiency; only the genetic chip production line of the existing scale of the synthetic preparation of the light deprotection original position that has of U.S. Affymetrix company patented technology provides commercial chip for demander; its main weak point is that distinctive smooth deprotection method need be made a series of specific photomasks; the cost height is not suitable for the short run demand.And must redesign photomask with different genetic chips to different user's requests.

At home, Southeast China University has developed molecular seal contact printing dna microarray original position synthetic technology, adopts the most ripe existing DNA synthetic route fully, is expected to reduce cost.But the synthetic preparation of the light deprotection original position that has with Affymetrix company on mask design patented technology is the same, at different user's requests and different genetic chips, must redesign mask and be used for preparing the PDMS molecular seal after the photoetching.

The utility model content

The purpose of this utility model is: at the deficiency that above prior art exists, propose that a kind of preparation technology is simple and direct, cost economy, genetic chip microorganism device easy to use, thus the process of applying of accelerated gene chip technology of preparing.

In order to reach above purpose, the technology implementation scheme that the utility model is taked is: by the method for the collapsible compound microarray that curls, genetic chip microorganism device is curled into coiled-type compound microarray rod, coiled-type compound microarray rod comprises porous rod and bonding film, described porous rod can be curled by film and form, also can be directly with the little rod of ready-made porous, on every porous rod, adhere to and be fixed with a kind of compound, and described porous rod is to be bonded on the bonding film according to the predetermined rule of arranging by chemical method.The film that will be bonded with porous rod then curls and to be folded into bar-shapedly, constitutes porous rod array chip rod, and porous rod array chip rod is cut into slices, and each section is a micro-array chip of chemical compound.

The method for preparing the curling collapsible compound microarray of the utility model comprises following technology:

1) preparation earlier is fixed with the porous rod of compound.Take two kinds of method preparations to be fixed with the porous rod of compound.

First method is: the application combination principles of chemistry, synthesize the compound molecule of pre-design at the bar-shaped material internal of porous and surface in situ, or the load in synthetic good compound solution of the bar-shaped material soaking of porous fixing the synthetic good compound molecule of pre-design;

Second method is: original position synthesizes the compound molecule of pre-design on the film like material, or membraneous material is immersed in the fixing synthetic good compound molecule of pre-design of of load in the synthetic good compound solution, then the film like material is rolled into the bar-shaped little rod of porous that is fixed compound.The method can avoid directly using the compound skewness phenomenon that diffusional resistance may cause in the bar-shaped material immobilized adduct molecule of porous.

2) the micropore club-shaped material that will be fixed with compound is bonded on the flexible diaphragm side by side, is curled into cylinder then or is folded into tetragonal prism, promptly obtains compound bars micro-array chip rod.

3) with above-claimed cpd rod microarray along cross-sectional slices, each section is the biochip of a correspondence.

Roll type micro-array chip of chemical compound rod of the present utility model has been exempted costliness in the original position synthetic technology and loaded down with trivial details mask manufacture process fully, do not need repeated positioning device yet, more do not need little valve fluid channel processing and corresponding high precision High-reliability Control system in the micro-fluid chip making, whole production and operating process and simple, do not need expensive equipment investment and personnel investment, thereby it is with low cost, and the liquid phase reactor environment arranged, ensure high coupling efficiency, obtained high effect.

Said method and to consume reagent very little, can significantly reduce cost, be applicable to the high flux screening of compound and combination thereof, biomolecule or medicine, the Study on Modernization of traditional Chinese medicine, simple and practical rapid and reliable clinical diagnosis, and genome or cDNA library screening, the discovery of new gene and the research of gene function, the research of proteomics etc.

In a word, the utility model will be accelerated the application of biochip in clinical diagnosis research greatly, accelerate the speed of new drug development greatly, reduce cost of development, raise the efficiency and accuracy, and the modernization of conventional medicament (comprising Chinese medicine) is had significant values.

Description of drawings

Fig. 1 is the utility model structural representation.

Fig. 2 is the utility model section synoptic diagram.

Among the figure, 1, porous rod; 2, film; 3, bonding film; 4, compound; 5, porous rod array chip rod.

Embodiment

Below in conjunction with the drawings and specific embodiments to the technical solution of the utility model is described in further detail.What should particularly point out is: in following examples, the contained base number of oligonucleotides is 8, and the oligonucleotide microarray dot matrix number that is synthesized is 16, pure just for principle of specification simply, be not so limited, the number that the contained base number of oligonucleotides can any existing dna synthesizer of as many as can reach in the actual demand, and the lattice point number can be very high in microarray dot matrix sum and the unit area, the level that can reach depends on the size of the small barred body of porous fully.It should also be noted that, material to the porous bar requires not have clear and definite restriction, only require they in the DNA building-up process except that utilizing first base of surface functional group coupling or fixing DNA probe, there is not chemical action to get final product each other with agents useful for same, others do not have any special requirement, can be any suitable organic or inorganic materials.For example the polypropylene of the teflon of glass fibre, polyester fiber, functionalization, functionalization, nylon etc. are natural and regenerated fiber etc.

Embodiment one:

The collapsible oligonucleotides porous rod micro-array chip rod 5 that curls comprises porous rod 1 and bonding film 3, described porous rod can be curled by film 2 and form, by original position is synthetic a kind of compound 4 is arranged on film 2, compound 4 is oligonucleotides materials, the surface of film 2 contains-OH ,-NH ₂Isoreactivity functional group also can have the above-mentioned functions group by method of modifying such as functional modification such as plasma treatment modification, chemical graft, hydrolysis, and described porous rod 1 is bonded on the bonding film 3 according to the predetermined rule of arranging.The film 2 that will be bonded with porous rod 1 then curls and is folded into bar-shapedly, constitutes porous rod array chip rod 5, and porous rod array chip rod is cut into slices, and each section is a micro-array chip of chemical compound.

Embodiment two:

The collapsible oligonucleotides porous rod micro-array chip rod 5 that curls comprises porous rod 1 and bonding film 3, described porous rod can be curled by film 2 and form, the fixing synthetic in advance good oligonucleotide probe of covalent coupling on film 2, again film is curled into the little rod of porous, be bonded in the little rod of porous on the inertia soft film then and be curled into the collapsible oligonucleotides porous rod micro-array chip rod that curls, then the corresponding genetic chip of section preparation.

Embodiment three:

The collapsible oligonucleotides porous rod micro-array chip rod 5 that curls comprises porous rod 1 and bonding film 3, and described porous rod can be directly to substitute with the little rod of porous, original position synthetic oligonucleotide on the little rod of porous, and the surface of the little rod of porous contains-OH ,-NH ₂Isoreactivity functional group, also can have the above-mentioned functions group by method of modifying such as functional modification such as plasma treatment modification, chemical graft, hydrolysis, be bonded in the little rod of porous on the inertia soft film then and be curled into the collapsible oligonucleotides porous rod micro-array chip rod that curls, then the corresponding genetic chip of section preparation.

Embodiment four:

The collapsible oligonucleotides porous rod micro-array chip rod 5 that curls comprises porous rod 1 and bonding film 3, described porous rod can be directly to substitute with the little rod of porous, directly covalent coupling is fixed synthetic in advance good oligonucleotide probe on the little rod of porous, to be fixed with the little rod of oligonucleotide probe porous again and be bonded on the inertia soft film and be curled into the collapsible oligonucleotides porous rod micro-array chip rod that curls, then the corresponding genetic chip of section preparation.

The remarkable advantage of above embodiment is that the curling collapsible oligonucleotides porous rod micro-array chip rod that is proposed has been exempted costliness in the existing oligonucleotide microarray original position synthetic technology and loaded down with trivial details mask manufacture process and resetting alignment device fully, when probe density when not being high especially, practical especially, efficient, succinct and cost is cheap.Owing in solution, react, not only ensured high coupling efficiency, help improving work efficiency, and to consume reagent very little, the advantage of this two aspect has significantly reduced cost.In a word, can obtain Cheap highly effective or cover a large amount of different compounds.In addition, also have a significant advantage to be, owing to adopt the collapsible bar-shaped microarray of porous that obtains, had only the film of fixation to link to each other between the chip probe lattice point that obtains, other zone is without any filler between the lattice point, so do not have background fluorescence and other background signal fully, conveniently especially should use up, methods such as electricity, heat, magnetic, sound, nanometer technology or chemistry etc. detected.Utilize these different compounds can carry out the qualitative or quantitative test of biochemical informations such as a large amount of genes or albumen.For example available ordinary optical microscope, laser confocal microscope, CCD observe or surperficial excimer resonance (SPR), the surface interferes reflection (RIFS), nanoparticle label to detect optics, electroporation and chemical methodes such as (mark-Yin dyes as gold), quartz crystal oscillator and detect, increase work efficiency greatly, reduce reagent dosage, really accomplish quick, real-time, accurate, robotization and pollution-free.It can be used for the high flux screening of compound and combination, biomolecule or medicine, the Study on Modernization of conventional medicament, and genome or cDNA library screening, the discovery of new gene and the research of gene function, the research of proteomics, and clinical detection etc.

The present invention will accelerate the speed of new drug development greatly, reduce cost of development, raise the efficiency and accuracy, and the modernization of conventional medicament (comprising Chinese medicine) is had significant values.Also will greatly promote biochip and spread to common clinical examination or other analysis monitoring department.

Claims (5)

1. collapsible micro-array chip of chemical compound rod that curls, comprise porous rod (1) and bonding film (3), it is characterized in that: described chip rod is the chip rod (5) that a kind of genetic chip microorganism device is curled into coiled-type compound microarray shape, be fixed with a kind of compound (4) in last adhering to of every porous rod (1), and described porous rod (1) is bonded on the bonding film (3) according to the predetermined rule of arranging by chemical method.

2. a kind of collapsible micro-array chip of chemical compound rod that curls according to claim 1, its feature also is: described porous rod (1) can be curled by film (2) and form, compound (4) is the oligonucleotides material, the surface of film (2) contains-OH ,-NH ₂Isoreactivity functional group.

3. a kind of collapsible micro-array chip of chemical compound rod that curls according to claim 1, its feature also is: described porous rod (1) can be curled by film (2) and form, and goes up the fixing synthetic in advance good oligonucleotide probe of covalent coupling at film (2).

4. a kind of collapsible micro-array chip of chemical compound rod that curls according to claim 1, its feature also is: described every porous rod (1) is the little rod of porous, directly covalent coupling is fixed synthetic in advance good oligonucleotide probe on the little rod of porous, and the little rod of oligonucleotide probe porous is bonded on the inertia soft film and is curled into the collapsible oligonucleotides porous rod micro-array chip rod that curls.

5. a kind of collapsible micro-array chip of chemical compound rod that curls according to claim 1, its feature also is: described every porous rod (1) is the little rod of porous, original position synthetic oligonucleotide on the little rod of porous, the surface of the little rod of porous contains-OH ,-NH ₂Isoreactivity functional group.

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