CN1109757C - Compound micro path array chip and its preparing method - Google Patents
Compound micro path array chip and its preparing method Download PDFInfo
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Abstract
The present invention relates to a microchannel array chip and a preparation method thereof, particularly to a compound microchannel array chip. The present invention is characterized in that: (a) a plurality of tiny through holes obtained by processing are arranged on a solid baseplate with a certain thickness, or a plurality of capillaries are stuck into a bundle by sticking materials; (b) specific chemical molecules comprising biomolecules are chemically or physically synthesized or assembled at the inner surface of each through hole in the (a); (c) microchannel blocks or rod-shaped materials with (a) and (b) characteristics are cut into thin sheets to obtain the corresponding compound microchannel chip.
Description
What the present invention relates to is a kind of micro path array chip and preparation method thereof, especially is compound micro path array chip.Wherein, contain specific chemical or biological substance on the chip in each microchannel.Here, compound is meant the organic molecule and the polymer of biological significance, nucleic acid, biomacromolecules such as albumen and composition thereof.
Compound micro path array chip is a kind of new biochip.Biochip mainly refers to the microarray that the biologically active substance (comprising nucleic acid, protein, cell and small tissue etc.) assembled constitutes in the solid chip, with realize to compound (comprising medicine), protein, nucleic acid, cell and other biological components accurately, fast, the screening or the detection of large information capacity.The principal feature of biochip comprises: (1) can assemble a large amount of (10 in a less solid chip
2～10
6Kind) biologically active substance, that obtains contains much information, the efficient height, and the biological reagent of consumption is few, can save a large amount of reagent expenses, and cost is low; (2) adopted plane and three-dimensional Micrometer-Nanometer Processing Technology, can reduce the preparation cost of single chip, realized producing in enormous quantities by improving integrated level; (3) can the pre-treatment of biological sample be extracted, amplification, reaction, and the information detection is mutually integrated, is prepared into miniature, full-automatic, pollution-free, as the to can be used for the microsample detection integrated intelligent biology chip of height.
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 biological compound detect and screening aspect time-consuming, effort, cost height, can not satisfy the demand.Traditional method is being carried out in the improved process, is that the biochip technology of representative arises at the historic moment with the gene chip.The strong means that provide are obtained and analyzed to the maturation of this technology and use and will bring a revolution for the exploitation and the life science association areas such as evaluation, food and environment of new drug for bioinformation.
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.Respectively different proteins, nucleic acid probe, cell strain or biological tissue are 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 Laboratory 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.This is existing a kind of method that is used for Biochemical Research and exploitation of generally using.In order to improve the efficient of drug screening, people pass through micro-processing technology, on substrates such as silicon, glass, plastics, make the check-out console that density is higher, the aperture is littler, different compounds or biomolecules or biological tissue are solidified among hole, and in detecting hole miniature detection probe such as preparation electrode.But this method still needs one by one different compounds, biomolecules etc. are assigned among each hole, can not mass and the stdn preparation, preparation process is still complicated, cost is higher, also be not easy to operate continuously fast simultaneously, more be not easy to simultaneously to multi-component continuous rapid detection in the sample.
The weak point that we not long ago exist at present conventional biochip and utensil, a kind of cell microarray chip has been proposed, this chip at first prepares the block materials of the parallel miniature hole array that contains cell, then along with the hole vertical direction on thinly slice.This method can realize the mass preparation of cell chip, can carry out the detection of multiple data quantity and multiparameter; Miniaturization, cost are low, pollution-free.
The object of the invention proposes a kind of new compound chip based on pipe array and preparation method thereof on above-mentioned cell microarray chip basis.This compound micro path array chip can strengthen the fluorescence excitation intensity of compound molecule widely, improve the sensitivity and the specificity that detect, but stdn and mass production, preparation cost is low, can carry out the continuous real-time analysis of multinomial index of biological activity to a large amount of compound molecules, sample and reagent consumption are little, the operation simple and feasible.
Compound pipe array chip is characterized in that (a) has at one to have arranged some micro-through-holes on the certain thickness solid substrate; (b) contain specific chemical molecular (comprising biomolecules) at each through hole.
Compound pipe array chip preparation method is characterized in that: this preparation method comprises following content:
(1) preparation of pipe array chip,
The preparation method one of A, pipe array chip,
A) method that adopts molding or injection moulding process or on a block materials, directly punch, prepare the block materials that an inside is distributed with the small hollow pipe that is arranged in parallel, small hollow pipe inside can be complete empty, also can be mesh structural porous weighting material or other particulate;
B) use rapid section machinery, block materials along being cut into parallel thin slice with the direction of microtubule with certain angle, is promptly made required micro path array chip;
The preparation method two of B, micro path array chip,
A) two-dimensional array is strained and be arranged into to a kind of or combination in hollow microchannel of employing such as small Glass tubing, metal tube, the polymer tube etc. to above-mentioned pipeline with an injection molding; Used microtubule surfaces externally and internally can further carry out coating modification and group of molecules finishing decorations with chemistry and physical method.As can further plating optical reflectance coating, with of the influence of the issuable fluorescent signal of the tackiness agent of isolating bonding microtubule to check and analysis.Another effect of metal plating is to strengthen the fluorescent signal that is used to detect in the microtubule, can strengthen 10 to 100 times usually;
B) inject mould with the inorganic materials of macromolecular material or thawing, conduits is solidified, be prepared into the block materials that inside is distributed with a large amount of hollow micro tube array; Or directly these hollow microtubules are bonded into an array of being made up of microtubule.May produce fluorescence and the Interference Detection analysis in testing process owing to be used for injection molding or adherent material, can in these materials, add some filler (as carbon black etc.) to eliminate this fluorescence interference.
C) section: use rapid section machinery, block materials is cut into parallel thin slice with the direction of microtubule with certain angle with the block materials edge, promptly make required micro path array chip;
(2) process of fixed compound
The process form one of A, fixed compound:
Require the inside of preparation among 2 (1) A (a) and the B (b) to be distributed with in the block materials of the small hollow pipe that is arranged in parallel at aforesaid right, respectively specific compound or the biomolecules of assembling in each small hollow pipe;
The process form two of B, fixed compound:
Inwall a kind of or combination in small hollow microchannel of each root that adopts in aforesaid right requirement 2 (1) B (a) such as small Glass tubing, metal tube, the polymer tube etc. is assembled specific compound or biomolecules respectively;
The process form three of C, fixed compound:
In each passage on the pipe array chip that aforesaid right requires to make among 2 (1) A (b) and the B (c), assemble specific compound or biomolecules respectively;
(3) fixed form of compound
A. the fixed form one of compound:
By the mode of physical fixation, specific compound or biomolecules are fixed in the microtubule;
B. the fixed form two of compound:
By the mode of chemical bond, specific compound or biomolecules are fixed on the inwall of microtubule;
C. the fixed form three of compound:
By the mode of combinatorial chemistry, directly synthetic specific compound or biological substance on the inwall of microtubule;
(4) with in the preparation form 2 (1) of above-mentioned pipe array chip any, make up with in the fixed form of any and 2 (3) compounds in the process form of above-mentioned 2 (2) fixed compounds any, just can prepare compound micro path array chip.
For ease of further practical application, compound micro path array chip proposed by the invention will further encapsulate, and compound micro path array chip is packaged between cover plate and the base plate.One of encapsulation cover plate form is that this encapsulation cover plate is furnished with the microfluid groove in the face of on the one side of chip, and this microfluid groove just in time is communicated with the micro-holes on the chip, and the input and output port of a pair of liquid is set; Two of encapsulation cover plate form goes up at hard plate material (as glass, plastics etc.) beats some through holes, and the number of micro-holes equates on the number of through hole and the chip, and the position of each through hole can be corresponding one by one with the position of last micro-holes, and on this cover plate covered with protective film.One of base plate form is to adopt mechanically resistant material to make, and its size is corresponding with die size; Two of base plate form is to adopt mechanically resistant material to make, and its size is corresponding with die size, and base plate is provided with microelectrode array, and microelectrode array is corresponding one by one with chip array; Three of base plate form also is to adopt mechanically resistant material to make, and its size is corresponding with die size, and sensor array (sonic transducer or thermal sensor or chemical sensor array) is set on base plate, and makes sensor array corresponding one by one with chip array.
For achieving the above object, the method for packing of the compound micro path array chip that the present invention provides is in any and the base plate form in any and the cover plate form in the said chip form any to be carried out combination package become one, just can obtain the structure formation of certain compound micro path array chip, promptly obtain the compound micro path array chip of different structure form by the various combination package of three kinds of parts, to satisfy the needs that different detection methods (as optical means, electrochemical method, sensor, method) detect.
Advantage of the present invention is that the micro-array chip of chemical compound that is proposed can carry out semiochemical qualitative or quantitative analyses such as a large amount of genes and albumen simultaneously on chip piece, and methods such as the gained result can use up, electricity, heat, sound or chemistry detect.For example available general opticmicroscope, laser confocal microscope, CCD observe or surperficial excimer resonance (SPR), and electroporations such as reflection optics such as (RIFS), electric current and current potential are interfered on the surface, and perhaps method such as thermistor, quartz crystal oscillator detects.Thereby increase work efficiency greatly, reduce reagent dosage, really accomplish fast, in good time, accurately, automatization and free of contamination detection.The microchannel that the small glass capillary of particularly using constitutes, the optical waveguide that Glass tubing forms, the fixed compound molecule can directly be subjected to exciting of its surperficial disappearance ripple on small glass capillary inwall, has strengthened its fluorescent emission intensity widely.Small glass capillary inwall is coated with the reflecting layer, with the influence of the issuable fluorescent signal of the tackiness agent of isolating bonding microtubule to check and analysis, and helps reducing the collection that excites reflection of light and molecular emission fluorescence, improves the sensitivity that detects greatly.In addition, little reaction of being carried out in each reacting pipe can be quickened and regulates and control by physical methods such as electricity, light, sound or heat, for example, microelectrode can be set respectively in each micro channel, comes little reaction on the control channel by the regulation and control electric field; By the size and Orientation of control current, required reactant is assembled or dispersion fast, or changed other physicochemical environment, improve detection sensitivity or shorten detection time.It can be used for the high flux screening of compound and combination, biomolecules 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 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.
Below in conjunction with accompanying drawing the specific embodiment of the present invention is described in further detail:
The compound micro path array chip synoptic diagram that Fig. 1 the present invention proposes.
One of the compound micro path array chip encapsulation cover plate that Fig. 2 the present invention proposes synoptic diagram.
Miniflow build compound micro path array chip synoptic diagram after the encapsulation that Fig. 3 the present invention proposes.
Two synoptic diagram of the compound micro path array chip encapsulation cover plate that Fig. 4 the present invention proposes.
Multi-hole type compound micro path array chip synoptic diagram after the encapsulation that Fig. 5 the present invention proposes.
The inwall that Fig. 6 the present invention proposes is fixed with the block materials synoptic diagram of a large amount of compound conduits.
The method synoptic diagram for preparing compound micro path array chip that Fig. 7 the present invention proposes.
The compound micro path array chip base plate synoptic diagram that Fig. 8 the present invention proposes.
In the above accompanying drawing, Fig. 1 is the synoptic diagram of a kind of compound micro path array chip of the present invention's proposition: it is to fix different compounds respectively during the small through hole on the chip is interior by compound micro path array chips 2 many and micro-through-hole 1 dense arrangement that the chip plane is angled.
A kind of compound micro path array chip encapsulation cover plate that Fig. 2 proposes for the present invention: can there be the cover plate 3 of microfluidic channel on its surface, this cover plate is provided with microfluid groove 4, when cover plate when having microfluid groove one cover on the compound micro path array chip corresponding with Fig. 1, microfluid groove on the cover plate just in time joins the micro through hole on the compound micro path array chip, makes the compound micro through hole site on the compound micro path array chip connect to a compound micro path array chip with microfluid input port 5 and output port 6 that seals by the microfluid gutter channel.
Fig. 3 is the miniflow build compound micro path array chip corresponding with Fig. 2, and detected liquid can directly enter into different compound micro paths by the input aperture 5 of microfluid pipeline, and wherein 7 is base plate.
Another compound micro path array chip encapsulation cover plate that Fig. 4 proposes for the present invention, has the corresponding fluid injection through hole of micropore on the compound micro path array chip corresponding on the cover plate with Fig. 1, wherein 8 is the compound micro path array chip through hole, and 9 are encapsulation multi-hole type cover plate.
Fig. 5 is the multi-hole type compound micro path array chip corresponding with Fig. 4; detected liquid can directly enter into different compound micro paths respectively by the fluid injection through hole, and wherein 7 is base plate, and 2 is compound micro path array chip; 9 are encapsulation multi-hole type cover plate, and 10 is protective membrane.
The inside that Fig. 6 proposes for the present invention is distributed with the block materials 12 of the tiny hollow pipe 11 of massive parallel, at each microtubule internal fixing different compound molecules.
Fig. 7 is the method for preparing compound micro path array chip that the present invention proposes: by the rapid section machine will be corresponding with Fig. 6 block materials 12 along thinly slicing on the directions perpendicular to microtubule, promptly made compound micro path array chip, wherein 13 is cutter.
The compound micro path array chip base plate that is provided with microelectrode array or sensor array 14 that Fig. 8 proposes for the present invention.
Further specify the present invention below in conjunction with several specific embodiments: embodiment one: the preparation of compound micro path array chip.1. the preparation of compound micro path array chip ():
1) at first utilize machining process (as the line cutting processing, technologies such as machining) or LIGA technology, the body silicon process technology, injection moulding complete processing etc. or mould of application additive method preparation with fine columnar arrays, each column is of a size of 100 μ m * 100 μ m.
2) use the raw material injection metal die of Shooting Technique, form the buik silicon elastomeric material that an inside is distributed with the small hollow pipe of massive parallel dense arrangement after the demoulding a kind of silicon rubber.
3) use micro-sampling method or other micro-apportioning method, with different compounds such as nucleic acid probe, protein etc. are introduced different ducts, are fixed on the duct wall at these molecules of suitable condition.(as shown in Figure 6)
4) use rapid section machinery, block materials is thinly sliced the buik silicon elastomeric material along certain angle, (as shown in Figure 7) promptly makes required compound micro path array chip.(as shown in Figure 1) the 2. preparation of compound micro path array chip (two):
1) at first utilizes some glass capillaries that clean up, in different glass capillaries, introduce different compounds such as nucleic acid probe, protein etc.
2) with an injection molding two-dimensional array is strained and be arranged into to the different glass kapillary, inject mould, be prepared into the block materials that inside is distributed with a large amount of glass capillary channel arrays with macromolecular material.
3) use rapid section machinery, the direction that block materials edge and microtubule is angled is thinly sliced, and promptly makes required chip.3. the preparation of encapsulation cover plate ():
Adopt complete processings such as machine drilling, laser boring, chemical corrosion to be processed into mobile microfluid groove for liquid in a side of hard plate material object chip, and the input and output port of a pair of liquid is set.(as shown in Figure 2) the 4. preparation of encapsulation cover plate (two):
Adopt complete processings such as machine drilling, laser boring, chemical corrosion to go up and beat some through holes at hard plate material (as glass, plastics etc.); the number of micro-holes equates on the number of through hole and the chip; and the position of each through hole can be corresponding one by one with the position of last micro-holes, and on this cover plate covered with protective film.5, the preparation of base plate ():
Adopt mechanically resistant material to make size and die size respective base.6, the preparation of base plate (two):
Adopt mechanically resistant material to make size and die size respective base, and base plate is provided with microelectrode array, microelectrode array is corresponding one by one with chip array.7, the preparation of base plate (three):
Adopt mechanically resistant material to make size and die size respective base, and sensor array (sonic transducer or thermal sensor or chemical sensor array) is set on base plate, and make sensor array corresponding one by one with chip array.8, encapsulation:
In any and the base plate form in any and the cover plate form in the said chip form any carried out combination package become one, just can obtain the structure formation of certain compound micro path array chip, be combined and packaged into the different structure form by three kinds of parts various, be of a size of the cell microarray chip of 2cm * 2cm, to satisfy the needs that different detection methods (as optical means, electrochemical method, sensor, method) detect.Embodiment two: genomic dna or the preparation of cDNA library chip
Different size gene or cDNA fragment are introduced different ducts in pipeline, make it fixing, and the direction that this block materials edge and microtubule is angled is thinly sliced; With being furnished with the microbody gutter channel or the porous hard plate material encapsulates, constitute genomic dna or cDNA library chip at last.
Application rapid section machinery is thinly sliced block materials to the buik silicon elastomeric material along certain angle, promptly makes required compound micro path array chip.Embodiment three: original position synthetic oligonucleotide probe micro path array chip
The preparation method of multitube road bulk glass kapillary silastic material is with embodiment one
A. the preparation of microfluid cover plate.A solid plate is processed into the template that the surface has concaveconvex structure.Then a capsule is placed on the template, calibrate the position at template and capsule edge.Going to the bottom of capsule is empty.When this capsule was placed on the template, template was positioned at the bottom of capsule, was provided with filling orifice on the top of capsule, injected silicon rubber (PDMS) raw material from this hole, and then PDMS is full of capsule in the end.After treating that PDMS solidifies, the PDMS together with the inside takes off on template carefully with capsule, and then PDMS has duplicated the concavo-convex pattern on the original template, and this moment, the microfluid cover plate was promptly made.Use the same method, prepare the microfluid cover plate of another piece correspondence.
B. prepare oligonucleotide probe array in the upper glass kapillary in multitube road bulk glass kapillary silastic material.After the cleaning of glass capillary inwall, drying, the benzole soln of putting into APTS (aminopropyltriethoxywerene werene) respectively reacted 2 hours, and the benzole soln of putting into succsinic acid in benzene after the rinsing again reacted 1 hour, thereby formed hydroxyl at glass surface.A pair of microfluid cover plate is individually fixed in multitube road bulk glass kapillary silastic material, makes its concaveconvex structure distribute corresponding with the kapillary of block materials.The Nucleotide that its 5 '-OH has been used two pairs of methoxies, three stupid methyl (DMT) protections is the anhydrous acetonitrile of dAdp and tetrazolium (catalyzer) for example, is injected in the multitube road bulk glass kapillary by the microfluid cover plate, makes it be connected glass surface.Slough protective material DMT on Nucleotide 5 ' on the substrate-OH by the acetonitrile solution that injects thiophenol (or trichoroacetic acid(TCA)) again, 5 '-OH is exposed.The DMT liquid that collection is sloughed is adjusted to certain volume, is that reference liquid detects DMT and absorbance value (OD value) in the 495nm place with the DMT-C1 monomer, according to the ratio of adjacent secondary OD value, can obtain the synthetic yield of this layer.Change again different microfluid cover plates and different mononucleotides (as dGdp, dCdp dTdp), repeats said process in different pipelines, but on the bonding second and third ... layer nucleic acid molecule.After being blended into 20 layers (i.e. oligonucleotide of 20 base length),,, form oligonucleotide arrays to remove the blocking group on base and the phosphoric acid with 30% ammonia treatment substrate.The chip water is washed down, and dry encapsulation is preserved.So far, preparation finishes.
Application rapid section machinery is thinly sliced block materials to the buik silicon elastomeric material along certain angle, promptly makes required compound micro path array chip.Embodiment four: original position synthetic peptide nucleic acid probe micro path array chip
(peptide nucleic acid is a kind of oligomerization N-2 amino-ethyl glycine (N-(2-aminoethyl glycine)) that has base PNA) to peptide nucleic acid(PNA), is that the polypeptide with Nucleotide character is stuck with paste like thing.PNA can with sequence complementary DNA, RNA and PNA hybridization, and its hybridization has high thermostability and to the high sensitivity of mispairing.Under certain conditions, can discern the mispairing of single base.Therefore, utilize the PNA sequence to prepare high-density gene array chip, can improve the hybridization accuracy and the Geng Mindu of gene chip greatly, have crucial application prospect.
A. the preparation of microfluid cover plate is with embodiment three A
B. prepare four kinds and contain thymus pyrimidine respectively, cytosine(Cyt), four kinds of bases of VITAMIN B4 and guanine can be used for PNA sequence synthetic monomer, it is the amino ethyl of N-2 bean butoxy carbonyl-N-thymus pyrimidine-1-acetyl glycine (Gly-T), N-2 bean butoxy carbonyl ethyl-N-cytosine(Cyt)-1-acetyl glycine (Gly-C), N-2 bean butoxy carbonyl ethyl-N-VITAMIN B4-1-acetyl glycine (Gly-A) and N-2 bean butoxy carbonyl ethyl-N-guanine-1-acetyl glycine (Gly-G).
C. prepare the oligopeptides nucleic acid probe array in the upper glass kapillary in multitube road bulk glass kapillary silastic material.After the cleaning of glass capillary inwall, drying, the benzole soln of putting into APTS (aminopropyltriethoxywerene werene) respectively reacted 2 hours, formed amido at glass surface.A pair of microfluid cover plate is individually fixed in multitube road bulk glass kapillary silastic material, makes its concaveconvex structure distribute corresponding with the kapillary of block materials.The PNA synthon that contains base, the solution of for example Gly-A, and pentafluorophenyl esters is injected in the multitube road bulk glass kapillary by the microfluid cover plate, makes it be connected glass surface.When the first layer is synthetic finish after, measure the coupling efficiency of the first layer with the hydration ninhydrin method.Change different microfluid cover plates again and inject PNA monomer such as the Gly-T that contains different bases, Gly-G, Gly-C and pentafluorophenyl esters mixing solutions repeat said process, form second and third ... layer PNA monomer molecule.After being blended into 20 layers (i.e. accurate peptide chains of the oligomerization of 20 base length), with 30%NaOH aqueous solution treatment substrate, to remove the blocking group on base and the phosphoric acid.The chip water is washed down, and dry encapsulation is preserved.So far, the preparation of original position synthetic peptide nucleic acid probe micro path array chip finishes.
Claims (4)
1. compound pipe array chip is characterized in that (a) has at one to have arranged some micro-through-holes on the certain thickness solid substrate; (b) contain specific chemical molecular at each through hole, comprise biomolecules.
2. compound pipe array chip preparation method, it is characterized in that: this preparation method comprises following content:
(1) preparation of pipe array chip,
The preparation method one of A, pipe array chip:
A) method that adopts molding or injection moulding process or directly punch on a block materials prepares the block materials that an inside is distributed with the small hollow pipe that is arranged in parallel, and small hollow pipe inside is complete empty, or mesh structural porous weighting material and other particulate;
B) use rapid section machinery, block materials along being cut into parallel thin slice with the direction of microtubule with certain angle, is promptly made required micro path array chip;
The preparation method two of B, micro path array chip:
A) adopt hollow microchannel, two-dimensional array is strained and be arranged into to above-mentioned pipeline with an injection molding;
Can further carry out coating modification and group of molecules finishing decorations inside and outside the used microtubule, as can further plating optical reflectance coating at surfaces externally and internally with chemistry and physical method;
B) inject mould with the inorganic materials of macromolecular material or thawing, conduits is solidified, be prepared into the block materials that inside is distributed with a large amount of hollow micro tube array; Or directly these hollow microtubules are bonded into an array of being made up of microtubule.
C) section: use rapid section machinery, block materials is cut into parallel thin slice with the direction of microtubule with certain angle with the block materials edge, promptly make required micro path array chip;
(2) process of fixed compound
The process form one of A, fixed compound:
Require the inside of preparation among 2 (1) A (a) and the B (b) to be distributed with in the block materials of the small hollow pipe that is arranged in parallel at aforesaid right, respectively specific compound or the biomolecules of assembling in each small hollow pipe;
The process form two of B, fixed compound:
In the small hollow microchannel of each root that aforesaid right requires to adopt among 2 (1) B (a), assemble specific compound or biomolecules respectively;
The process form three of C, fixed compound:
In each passage on the pipe array chip that aforesaid right requires to make among 2 (1) A (b) and the B (c), assemble specific compound or biomolecules respectively;
(3) fixed form of compound
A. the fixed form one of compound:
By the mode of physical fixation, specific compound or biomolecules are fixed in the microtubule;
B. the fixed form two of compound:
By the mode of valence bond, specific compound or biomolecules are fixed on the inwall of microtubule;
C. the fixed form three of compound:
By the mode of combinatorial chemistry, directly synthetic specific compound or biological substance on the inwall of microtubule;
(4) with in the preparation form 2 (1) of above-mentioned pipe array chip any, make up with in the fixed form of any and 2 (3) compounds in the process form of 2 (2) fixed compounds any, just can prepare compound micro path array chip;
(5) compound micro path array chip encapsulation, compound micro path array chip is packaged between cover plate and the base plate
One of encapsulation cover plate form:
Encapsulation cover plate is furnished with the microfluid groove in the face of on the one side of chip, and this microfluid groove just in time is communicated with the micro-holes on the chip, and the input and output port of a pair of liquid is set;
Encapsulation cover plate form two:
Beat some through holes on hard plate material, the number of micro-holes equates on the number of through hole and the chip, and the position of each through hole can be corresponding one by one with the position of last micro-holes;
One of base plate form:
The employing mechanically resistant material is made, and the base plate size is corresponding with die size;
Two of base plate form:
The base plate size is corresponding with die size; And base plate is provided with microelectrode array, and microelectrode array is corresponding one by one with chip array;
Three of base plate form:
The base plate size is corresponding with die size, and sensor array is set on base plate, and makes sensor array corresponding one by one with chip array.
3. compound micro path array chip preparation method according to claim 2, it is characterized in that hollow microchannel can adopt a kind of or combination in small Glass tubing, metal microtubule, the polymer microtubule, can further carry out coating modification and group of molecules finishing decorations inside and outside the microtubule with chemistry and physical method.
4. compound micro path array chip preparation method according to claim 2 is characterized in that the inorganic materials that is used for injection molding or adherent macromolecular material or thawing can add filler.
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