CN106799196A - DNA fabricated in situ semiconductor chip and its control method - Google Patents
DNA fabricated in situ semiconductor chip and its control method Download PDFInfo
- Publication number
- CN106799196A CN106799196A CN201510844308.9A CN201510844308A CN106799196A CN 106799196 A CN106799196 A CN 106799196A CN 201510844308 A CN201510844308 A CN 201510844308A CN 106799196 A CN106799196 A CN 106799196A
- Authority
- CN
- China
- Prior art keywords
- solution
- platinum electrode
- dna
- base
- buffer
- 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
Links
Classifications
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J19/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
- B01J19/08—Processes employing the direct application of electric or wave energy, or particle radiation; Apparatus therefor
- B01J19/087—Processes employing the direct application of electric or wave energy, or particle radiation; Apparatus therefor employing electric or magnetic energy
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J19/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
- B01J19/0093—Microreactors, e.g. miniaturised or microfabricated reactors
-
- C—CHEMISTRY; METALLURGY
- C40—COMBINATORIAL TECHNOLOGY
- C40B—COMBINATORIAL CHEMISTRY; LIBRARIES, e.g. CHEMICAL LIBRARIES
- C40B60/00—Apparatus specially adapted for use in combinatorial chemistry or with libraries
- C40B60/14—Apparatus specially adapted for use in combinatorial chemistry or with libraries for creating libraries
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J2219/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
- B01J2219/00274—Sequential or parallel reactions; Apparatus and devices for combinatorial chemistry or for making arrays; Chemical library technology
- B01J2219/00277—Apparatus
- B01J2219/00497—Features relating to the solid phase supports
- B01J2219/00527—Sheets
- B01J2219/00529—DNA chips
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J2219/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
- B01J2219/00274—Sequential or parallel reactions; Apparatus and devices for combinatorial chemistry or for making arrays; Chemical library technology
- B01J2219/00583—Features relative to the processes being carried out
- B01J2219/00603—Making arrays on substantially continuous surfaces
- B01J2219/00605—Making arrays on substantially continuous surfaces the compounds being directly bound or immobilised to solid supports
- B01J2219/00608—DNA chips
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J2219/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
- B01J2219/00274—Sequential or parallel reactions; Apparatus and devices for combinatorial chemistry or for making arrays; Chemical library technology
- B01J2219/00709—Type of synthesis
- B01J2219/00713—Electrochemical synthesis
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J2219/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
- B01J2219/00274—Sequential or parallel reactions; Apparatus and devices for combinatorial chemistry or for making arrays; Chemical library technology
- B01J2219/00718—Type of compounds synthesised
- B01J2219/0072—Organic compounds
- B01J2219/00722—Nucleotides
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J2219/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
- B01J2219/08—Processes employing the direct application of electric or wave energy, or particle radiation; Apparatus therefor
- B01J2219/0803—Processes employing the direct application of electric or wave energy, or particle radiation; Apparatus therefor employing electric or magnetic energy
- B01J2219/0805—Processes employing the direct application of electric or wave energy, or particle radiation; Apparatus therefor employing electric or magnetic energy giving rise to electric discharges
- B01J2219/0807—Processes employing the direct application of electric or wave energy, or particle radiation; Apparatus therefor employing electric or magnetic energy giving rise to electric discharges involving electrodes
- B01J2219/0809—Processes employing the direct application of electric or wave energy, or particle radiation; Apparatus therefor employing electric or magnetic energy giving rise to electric discharges involving electrodes employing two or more electrodes
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J2219/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
- B01J2219/08—Processes employing the direct application of electric or wave energy, or particle radiation; Apparatus therefor
- B01J2219/0803—Processes employing the direct application of electric or wave energy, or particle radiation; Apparatus therefor employing electric or magnetic energy
- B01J2219/0805—Processes employing the direct application of electric or wave energy, or particle radiation; Apparatus therefor employing electric or magnetic energy giving rise to electric discharges
- B01J2219/0807—Processes employing the direct application of electric or wave energy, or particle radiation; Apparatus therefor employing electric or magnetic energy giving rise to electric discharges involving electrodes
- B01J2219/0815—Processes employing the direct application of electric or wave energy, or particle radiation; Apparatus therefor employing electric or magnetic energy giving rise to electric discharges involving electrodes involving stationary electrodes
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J2219/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
- B01J2219/08—Processes employing the direct application of electric or wave energy, or particle radiation; Apparatus therefor
- B01J2219/0803—Processes employing the direct application of electric or wave energy, or particle radiation; Apparatus therefor employing electric or magnetic energy
- B01J2219/0805—Processes employing the direct application of electric or wave energy, or particle radiation; Apparatus therefor employing electric or magnetic energy giving rise to electric discharges
- B01J2219/0807—Processes employing the direct application of electric or wave energy, or particle radiation; Apparatus therefor employing electric or magnetic energy giving rise to electric discharges involving electrodes
- B01J2219/0837—Details relating to the material of the electrodes
- B01J2219/0841—Metal
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Health & Medical Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Toxicology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Biochemistry (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Molecular Biology (AREA)
- Apparatus Associated With Microorganisms And Enzymes (AREA)
Abstract
The invention discloses a kind of semiconductor chip for DNA fabricated in situ, including reaction zone, control unit, substrate and pin, the reaction zone includes organic poly layer and the electrod-array being made up of at least one platinum electrode, the electrod-array is arranged for ranks, described control unit controls line and alignment, the line is connected to the platinum electrode by switching device, and the alignment is connected to the switching device and controls the break-make of the switching device, and the platinum electrode is placed in into high potential；A kind of control method based on said chip is also disclosed, the fabricated in situ of DNA is realized by controlling the current potential of platinum electrode.Semiconductor chip and its control method provided by the present invention for DNA fabricated in situ can realize accurate, stabilization the fabricated in situ of DNA with reference to computer technology, substantially reduce production cost.
Description
Technical field
The present invention relates to DNA synthesis, more particularly to a kind of DNA fabricated in situ semiconductor chip and its control method.
Background technology
Genetic chip (gene chip, DNA chip, the DNA microarray) DNA chip that is otherwise known as, DNA are micro-
Array or biochip, refer to the nucleic acid piece obtained with a large amount of artificial synthesized or application conventional molecular biological technology
Duan Zuowei probes, are fixed on silicon chip, slide or plastic sheet according to specific arrangement mode and specific means,
The probe arranged on one chip of nail cover size can up to up to ten thousand.When in use, the sample that will first be studied
Product are marked, and are then hybridized with the oligonucleotide probe on chip, then with equipment such as laser confocal microscopes to core
Piece is scanned, and coupled computer software systems detect the power of hybridization signal, so as to obtain efficiently and on a large scale
Related biological information.Be also secured to substantial amounts of nucleic acid molecules on carrier by technique, once can detect analysis
Substantial amounts of DNA and RNA, solves that traditional nucleic acid blot hybridization technique is complicated, automaticity is low, detection target
The shortcoming that molecular amounts are few, high cost, efficiency are low.
In addition, by designing different probe arrays (array), DNA sequence dna is rebuild using hybridization spectrum, can also be real
Existing sequencing by hybridization (sequencing by hybridization, SBH).At present, the technology gene expression research,
The fields such as genome research, sequence analysis and gene diagnosis have shown that important theory and application value.
, there is various chips technology in constantly improve and development with biochip technology.The main mesh of initial chip
Mark be identified for the measure of DNA sequence dna, gene expression atlas and gene mutation body monitoring and analysis, therefore
Referred to as genetic chip.But current this technology has expanded to non-nucleic acid field, has such as occurred in that ProteinChip Analysis
Technology, Biacore technologies and screen printing technique etc..Under this development trend, chip technology now more to be referred to as
Biochip technology.Biochip technology is the extension of conventional molecular hybridization in molecular biology.It does substantially
Method is that substantial amounts of nucleic acid fragment is fixed on certain medium regularly, is made chip, the sample that then will be detected
Product are marked, then are fully hybridized with the chip made, and are eluted, and are shown with image.It is applied at present
Making the carrier material of chip mainly has what semi-conductor silicon chip, sheet glass, sheet metal, various organic polymers made
Film etc..
Genetic chip typically has two kinds of preparation methods.One kind is synthesis post-crosslinking (post-synthetic
Attachment), it is used for large fragment DNA, oligonucleotides even mRNA is also suitable for sometimes；Another kind is original
Position synthesis (in-situ synthesis), is suitable for oligonucleotides.Wherein, common in-situ synthetic method has light
Lead in-situ synthesis, voltage impact system, fluid passage synthetic method, molecular stamping method and mechanical. points coating.These sides
Method running cost is very high, and technique is complex, and repeatability is poor, and the quantity of probe can be received in unit area
To the limitation of technology.
The invention provides a kind of semiconductor chip and its control method for DNA fabricated in situ, by computer
The current potential of control chip Top electrode realizes the stabilization of DNA, accurate fabricated in situ, and then realizes the automatic original of DNA
Position synthesis.
The content of the invention
In view of the drawbacks described above of prior art, it is in situ that the technical problems to be solved by the invention are to provide a kind of DNA
Synthesis semiconductor chip and its control method, realize the accurate fabricated in situ of DNA of computer controls.
Specifically, the invention provides a kind of semiconductor chip for DNA fabricated in situ, it is characterised in that
Including reaction zone, control unit, substrate and pin, the reaction zone includes organic poly layer and by least one platinum
The electrod-array that electrode is constituted, the platinum electrode is arranged at the substrate, and organic many poly layer are covered in the base
Plate surface and the electrod-array, described control unit the connection pin and the electrod-array, for selecting
State the platinum electrode in electrod-array and be placed on high potential；The electrod-array is arranged for ranks, and the control is single
Unit control line and alignment, the line are connected to the platinum electrode by switching device, and the alignment is connected to institute
State switching device and control the break-make of the switching device.
Further, the high potential is+3V~+15V.
Further, organic many poly layer have base sequence connection end in the opposite side of the electrod-array, should
Base sequence connection end is connected with blocking group, and the blocking group is sloughed in alkaline electrolyte solution.
Present invention also offers a kind of control method based on the above-mentioned semiconductor chip for DNA fabricated in situ,
Including
Electrolyte solution is covered in the outer surface of the reaction zone of the electrochemical chip；
The selected corresponding line of platinum electrode is placed in high potential by described control unit；
Make described control unit by the selected corresponding switch device conductive of the corresponding alignment of platinum electrode, so that select
Platinum electrode is placed in high potential by corresponding line；
Hydrogen ion is produced in selected platinum electrode surrounding them, reaction solution；
It is connected to what the blocking group of the electrochemical chip surface base sequence connection end was provided in the hydrogen ion
Sloughed in local sour environment；
The line and the current potential of alignment operated before recovery, so as to recover the current potential of the electrode；
The electrolyte solution of the outer surface of the reaction zone is replaced with into reaction solution, the reaction solution is in alkaline and molten
Solution has one end to be connected with the base of blocking group；
The base that described one end is connected with base protecting group is connected to the base sequence connection end；
Remove the reaction solution.
Further, the electrolyte solution of the outer surface by the reaction zone replaces with reaction solution, described anti-
Liquid is answered in alkalescence and is dissolved with one end and is connected with the base of blocking group and include
Draw the electrolyte solution；
Use the outer surface of reaction zone described in the first wash buffer；
Reaction solution is covered in the outer surface of the reaction zone, wherein being dissolved with the base that one end is connected with blocking group.
Further, first buffer solution be acetate buffer, carbonate buffer solution, citrate buffer,
HEPES buffer solution, MOPS buffer solutions, phosphate buffer, TRIS buffer solutions or potassium iodate solution.
Further, the reaction solution is in alkalescence.
Further, the removal reaction solution includes
Draw the reaction solution；
Use the outer surface of reaction zone described in the second wash buffer.
Further, second buffer solution be acetate buffer, carbonate buffer solution, citrate buffer,
HEPES buffer solution, MOPS buffer solutions, phosphate buffer, TRIS buffer solutions or potassium iodate solution.
Semiconductor chip and its control method provided by the present invention for DNA fabricated in situ can combine computer skill
Art realizes accurate, stabilization the fabricated in situ of DNA, substantially reduces production cost.
The technique effect of design of the invention, concrete structure and generation is described further below with reference to accompanying drawing,
To be fully understood from the purpose of the present invention, feature and effect.
Brief description of the drawings
Fig. 1 is arrangement schematic diagram of the platinum electrode on base plate on a kind of electrochemical chip；
Fig. 2 is a kind of primary structure schematic diagram of electrochemical chip；
Fig. 3 is the position view of platinum electrode and high molecular polymer on base plate on electrochemical chip；
The blocking group that Fig. 4 shows the base sequence connection end on high molecular polymer surface and connects thereon；
Fig. 5 is schematic diagram when electrochemical chip surface is coated with electrolyte solution；
Fig. 6 is reaction schematic diagram when left side platinum electrode in Fig. 5 to be placed in high potential；
Fig. 7 is the schematic diagram when electrolyte solution in Fig. 6 to be replaced with reaction solution, and wherein platinum electrode is in low electricity
Position；
Fig. 8 is the reaction schematic diagram that the base that 5 ' ends are protected is connected to de- de-protected base sequence connection end；
Fig. 9 is the schematic diagram when reaction solution in Fig. 8 to be replaced with electrolyte solution；
Figure 10 is to continue with being placed in left side platinum electrode in Fig. 5 reaction schematic diagram during high potential；
Figure 11 is the schematic diagram when electrolyte solution in Figure 10 to be replaced with reaction solution, and wherein platinum electrode is low
Current potential；
Figure 12 is that the base of 5 ' end protections is connected to and is already attached to base sequence connection end and has sloughed guarantor in advance
The reaction schematic diagram of the base of shield；
Figure 13 is the schematic diagram when reaction solution in Figure 12 to be replaced with electrolyte solution；
Figure 14 is reaction schematic diagram when right side platinum electrode in Fig. 5 to be placed in high potential；
Figure 15 is the schematic diagram when electrolyte solution in Figure 14 to be replaced with reaction solution, and wherein platinum electrode is low
Current potential；
Figure 16 is the reaction schematic diagram that the base that 5 ' ends are protected is connected to de- de-protected base sequence connection end；
Figure 17 is reaction solution and with the schematic diagram on wash buffer electrochemical chip surface, wherein platinum in removal Figure 16
Electrode is in low potential；
In Fig. 1-Figure 17,1- substrates, 2- platinum electrodes, 21- alignments, 22- lines, 23- triodes, 3- macromolecules
Polymer, 4- base sequences connection end, 5- blocking groups, 6- electrolyte solutions, the base of 7-5 ' ends protection, 8-
Reaction solution, 9- takes off de-protected base.
Specific embodiment
Embodiments of the invention are described below in detail, the example of the embodiment is shown in the drawings, wherein ad initio extremely
Same or similar label represents same or similar element or the element with same or like function eventually.Lead to below
It is exemplary to cross the embodiment being described with reference to the drawings, it is intended to for explaining the present invention, and it is not intended that to this hair
Bright limitation.
In the description of the invention, it is to be understood that term " " center ", " longitudinal direction ", " transverse direction ", " length ",
" width ", " thickness ", " on ", D score, "front", "rear", "left", "right", " vertical ", " level ",
The orientation or position relationship of the instruction such as " top ", " bottom " " interior ", " outward ", " clockwise ", " counterclockwise " be based on
Orientation shown in the drawings or position relationship, be for only for ease of description the present invention and simplify describe, rather than indicate or
Imply signified device or element and must have specific orientation, with specific azimuth configuration and operation, therefore can not
It is interpreted as limitation of the present invention.
Additionally, term " first ", " second " are only used for describing purpose, and it is not intended that indicating or implying relative
Importance or the implicit quantity for indicating indicated technical characteristic.Thus, " first ", " second " are defined
One or more this feature can be expressed or be implicitly included to feature.In the description of the invention, " multiple "
Two or more are meant that, unless otherwise expressly limited specifically.
In the present invention, unless otherwise clearly defined and limited, term " installation ", " connected ", " connection ",
Terms such as " fixations " should be interpreted broadly, for example, it may be being joined directly together, it is also possible to indirect by intermediary
It is connected.For the ordinary skill in the art, can as the case may be understand above-mentioned term in the present invention
In concrete meaning.
In the present invention, unless otherwise clearly defined and limited, fisrt feature second feature it " on " or it
D score can include the first and second feature directly contacts, it is also possible to including the first and second features not be directly to connect
Touch but by the other characterisation contact between them.And, fisrt feature second feature " on ", " on
Side " and " above " directly over second feature and oblique upper, or are merely representative of fisrt feature water including fisrt feature
Flat height is higher than second feature.Fisrt feature second feature " under ", " lower section " and " below " include first
Feature is directly over second feature and oblique upper, or is merely representative of fisrt feature level height less than second feature.
Fig. 1 is a kind of structural representation of the substrate 1 of electrochemical chip, is provided with the array of platinum electrode 2.
As shown in Fig. 2 being coated with high molecular polymer 3 on the surface of substrate 1 and platinum electrode 2, thickness is 10-30 μm.
DNA fabricated in situ is to be carried out in the upper surface of the shown position of high molecular polymer 3.
Fig. 3 shows the relative position relation of substrate 1, platinum electrode 2 and high molecular polymer 3, wherein platinum electrode
2 are also connected with transistor collector, and emitter stage and base stage are connected to line 22 and alignment 21.Platinum electrode 2
Current potential is to be controlled by line 22 and alignment 21：When needing to improve the current potential of platinum electrode 2, by line
22 are placed in high potential, and are turned it in the making alive of base stage 21.Three poles in Fig. 3 are eliminated in Fig. 4-Figure 17
Pipe is not drawn into, and the current potential for improving a certain platinum electrode is by this operation.
Wherein, line 22 and alignment 21 are by control unit control.Control unit receives from the pin of chip
Signal from after the coding of computer, by decoding obtain need operation row/column address.
It should be noted that having special construction on the top layer of high molecular polymer 3, i.e., its surface has base sequence
Connection end 4, base sequence connection end 4 is connected with blocking group 5.Its structure figure 4 illustrates.It is adjacent
The distance between center of platinum electrode 2 is 300 μm.Although also having identical structure between adjacent platinum electrode 2,
But because being not related to during fabricated in situ, therefore have been omitted from.
Such as Fig. 5, one layer of (NaCO of electrolyte solution 6 is covered on the surface of high molecular polymer 33Solution, its concentration is
0.05mol/L), overwrite procedure be by electrolyte solution 6 be filled with the surface of high molecular polymer 3 setting reative cell (not
Show).The solution covering and flushing of follow-up each step are carried out by being filled with solution in such reative cell, no
Repeat again.Electrolyte solution 6 is presented alkalescence, and its pH is about 9.Blocking group 5 can't in alkaline environment
Slough, but can be sloughed in sour environment.
For purposes of illustration only, the present embodiment is illustrated by taking two adjacent platinum electrodes as an example, but this does not imply that participation is anti-
There is the requirement of any position relationship between the platinum electrode answered；In fact, in actual mechanical process, it is anti-described in this example
Answering process can occur in any platinum electrode position being arranged on substrate.
As shown in fig. 6, being powered to the platinum electrode 2 in left side, its current potential to+5V is improved, in the electricity of its correspondence position
Meeting localized clusters H+ ions in electrolyte solution, so as to form acidic micro-environment, connect correspondence position base sequence
The blocking group 5 that end 4 is connected is sloughed, and the base sequence connection end near right side platinum electrode 2 is unaffected.
Galvanization lasts about 8s.Recover the current potential of all energization platinum electrodes 2.
The surface of high molecular polymer 3 is rinsed with HEPES cushioning liquid, then as shown in Figure 7 in high molecular polymer
The covering of 3 surfaces is dissolved with the reaction solution 8 of the base 7 of 5 ' end protections.So, the 3 ' of the base 7 of 5 ' end protections
End is connected to the base sequence connection end 4 for having sloughed blocking group 5, the base without sloughing blocking group 5
Sequence connection end 4 can not then connect the base 7 of 5 ' end protections, such as Fig. 8.Base can be guanine, gland herein
Any one in purine, cytimidine, thymidine.
Such as Fig. 9, the surface three times of high molecular polymer 3 is rinsed with HEPES cushioning liquid, then to cover electrolyte molten
Liquid 6.At this time, it may be necessary to 5 ' the end protections that the high molecular polymer 3 on the surface of platinum electrode 2 in left side has been connected
The end of base 7 continue connect base.Then, as shown in Figure 10 will left side platinum electrode 2 be placed in+5V, it is and foregoing
Process is similar to, the base 7 of 5 ' the end protections that the local sour environment of the H+ formation of small range aggregation is connected before being allowed to
The blocking group 5 for being connected is sloughed.
The surface of high molecular polymer 3 is rinsed with HEPES cushioning liquid, then as shown in figure 11 in high molecular polymerization
The covering of the surface of thing 3 is dissolved with the reaction solution 8 of the base 7 of 5 ' end protections.Base can be fast for guanine, gland herein
Any one in purine, cytimidine, thymidine.
Such as Figure 12, the base 7 of follow-up 5 ' the end protections for adding is connected to foregoing sloughed blocking group and has connected
In in the base of base sequence connection end 4.
The surface three times of high molecular polymer 3 is rinsed using HEPES cushioning liquid, then covers electrolyte solution 6.
The surface of high molecular polymer 3 connection base corresponding in right side platinum electrode is now needed, then by right side platinum electrode 2
+ the 5V of high potential, such as Figure 14 are placed in, local sour environment makes the blocking group that base sequence connection end 4 connects
5 slough.
The surface of high molecular polymer 3 is rinsed with HEPES cushioning liquid, then as shown in figure 15 in high molecular polymerization
The covering of the surface of thing 3 is dissolved with the reaction solution 8 of the base 7 of 5 ' end protections.Base can be fast for guanine, gland herein
Any one in purine, cytimidine, thymidine.3 ' ends of the base 7 of 5 ' the end protections then added herein are such as
Base sequence connection end 4 is connected to shown in Figure 16.
The surface three times of high molecular polymer 3 is rinsed using HEPES cushioning liquid, now in high molecular polymer 3
Surface obtains length and is respectively 2 bases and 3 the two of base kinds of base chains, such as Figure 17.Base can be fast for bird
Any one in purine, adenine, cytimidine, thymidine.
Above step is described by the current potential for changing platinum electrode 2 so as to connect base on the surface of high molecular polymer 3
Process.The more complicated base chain for practical purpose of composite structure subsequently is needed, can repeat above-mentioned similar
Process, until obtaining required base chain, can be used to test or diagnostic purpose, for example make DNA probe.
Preferred embodiment of the invention described in detail above.It should be appreciated that one of ordinary skill in the art
Just many modifications and variations can be made with design of the invention without creative work.Therefore, all this technology necks
Technical staff passes through logic analysis, reasoning or limited on the basis of existing technology under this invention's idea in domain
Available technical scheme is tested, all should be in the protection domain being defined in the patent claims.
Claims (9)
1. a kind of semiconductor chip for DNA fabricated in situ, it is characterised in that single including reaction zone, control
Unit, substrate and pin, the reaction zone include organic poly layer and the electricity being made up of at least one platinum electrode
Pole array, the platinum electrode is arranged at the substrate, and organic many poly layer are covered in the substrate surface
And the electrod-array, described control unit the connection pin and the electrod-array, for selecting
State the platinum electrode in electrod-array and be placed on high potential；The electrod-array is arranged for ranks, described
Control unit controls line and alignment, and the line is connected to the platinum electrode by switching device, described
Alignment is connected to the switching device and controls the break-make of the switching device.
2. the semiconductor chip for DNA fabricated in situ according to claim 1, it is characterised in that institute
High potential is stated for+3V~+15V.
3. the semiconductor chip for DNA fabricated in situ according to claim 1, it is characterised in that institute
The opposite side that organic many poly layer are stated in the electrod-array has base sequence connection end, and the base sequence connects
Connect end and be connected with blocking group, the blocking group is sloughed in alkaline electrolyte solution.
4. a kind of semiconductor chip for DNA fabricated in situ based on according to claim any one of 1-3
Control method, it is characterised in that including
A) outer surface in the reaction zone of the electrochemical chip covers electrolyte solution；
B) the selected corresponding line of platinum electrode is placed in high potential by described control unit；
C) described control unit is made by the selected corresponding switch device conductive of the corresponding alignment of platinum electrode, so as to select
Fixed platinum electrode is placed in high potential by corresponding line；
D) hydrogen ion is produced in selected platinum electrode surrounding them, reaction solution；
E) blocking group for being connected to the electrochemical chip surface base sequence connection end is carried in the hydrogen ion
Sloughed in the local sour environment of confession；
F) line and the current potential of alignment operated before recovering, so as to recover the current potential of the electrode；
G) electrolyte solution of the outer surface of the reaction zone is replaced with into reaction solution, the reaction solution is in alkalescence
And it is dissolved with the base that one end is connected with blocking group；
H) described one end is connected with the base of base protecting group and is connected to the base sequence connection end；
I) reaction solution is removed；
J) repeat step a) is to i), until synthesizing required base sequence near required platinum electrode.
5. control method according to claim 4, it is characterised in that step g) is by the outside of the reaction zone
The electrolyte solution on surface replaces with reaction solution, and the reaction solution is in alkalescence and is dissolved with one end and is connected with protection
The base of group includes
Draw the electrolyte solution；
Use the outer surface of reaction zone described in the first wash buffer；
Reaction solution is covered in the outer surface of the reaction zone, wherein being dissolved with the alkali that one end is connected with blocking group
Base.
6. control method according to claim 5, it is characterised in that first buffer solution is slow for acetate
Fliud flushing, carbonate buffer solution, citrate buffer, HEPES buffer solution, MOPS buffer solutions,
Phosphate buffer, TRIS buffer solutions or potassium iodate solution.
7. control method according to claim 5, it is characterised in that the reaction solution is in alkalescence.
8. control method according to claim 4, it is characterised in that step i) removes the reaction solution to be included
Draw the reaction solution；
Use the outer surface of reaction zone described in the second wash buffer.
9. control method according to claim 8, it is characterised in that second buffer solution is slow for acetate
Fliud flushing, carbonate buffer solution, citrate buffer, HEPES buffer solution, MOPS buffer solutions,
Phosphate buffer, TRIS buffer solutions or potassium iodate solution.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201510844308.9A CN106799196A (en) | 2015-11-26 | 2015-11-26 | DNA fabricated in situ semiconductor chip and its control method |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201510844308.9A CN106799196A (en) | 2015-11-26 | 2015-11-26 | DNA fabricated in situ semiconductor chip and its control method |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN106799196A true CN106799196A (en) | 2017-06-06 |
Family
ID=58977276
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201510844308.9A Pending CN106799196A (en) | 2015-11-26 | 2015-11-26 | DNA fabricated in situ semiconductor chip and its control method |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN106799196A (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN112662660A (en) * | 2020-12-11 | 2021-04-16 | 复旦大学 | Electrode array device for gene sequence synthesis and control method thereof |
Citations (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1274758A (en) * | 1999-05-21 | 2000-11-29 | 陆祖宏 | Compound micro-array chip preparing process and the micro-array chip using the same |
| CN1290752A (en) * | 2000-10-10 | 2001-04-11 | 陆祖宏 | Compound micro path array chip and its preparing method |
| CN1337580A (en) * | 2000-08-08 | 2002-02-27 | 清华大学 | Solid molecule operating method in microfluid system |
| US20030054344A1 (en) * | 1999-03-11 | 2003-03-20 | Rossi Francis M. | Method for generating ultra-fine spotted arrays |
| TW593334B (en) * | 1996-07-05 | 2004-06-21 | Combimatrix Corp | Electrochemical solid phase synthesis of polymers |
| CN101495838A (en) * | 2005-08-05 | 2009-07-29 | 奥本大学 | Reversible electrochemical sensors for polysions |
| US8603803B2 (en) * | 2006-12-28 | 2013-12-10 | Intel Corporation | Solid phase electrochemical synthesis with controlled product cleavage |
| CN103472123A (en) * | 2013-09-30 | 2013-12-25 | 湖南师范大学 | In-situ anode dissolving-out volt-ampere analytical method based on metal marking and biology affinity |
| CN103945931A (en) * | 2011-09-26 | 2014-07-23 | 基因技术股份公司 | High efficiency, small volume nucleic acid synthesis |
-
2015
- 2015-11-26 CN CN201510844308.9A patent/CN106799196A/en active Pending
Patent Citations (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| TW593334B (en) * | 1996-07-05 | 2004-06-21 | Combimatrix Corp | Electrochemical solid phase synthesis of polymers |
| US20030054344A1 (en) * | 1999-03-11 | 2003-03-20 | Rossi Francis M. | Method for generating ultra-fine spotted arrays |
| CN1274758A (en) * | 1999-05-21 | 2000-11-29 | 陆祖宏 | Compound micro-array chip preparing process and the micro-array chip using the same |
| CN1337580A (en) * | 2000-08-08 | 2002-02-27 | 清华大学 | Solid molecule operating method in microfluid system |
| CN1290752A (en) * | 2000-10-10 | 2001-04-11 | 陆祖宏 | Compound micro path array chip and its preparing method |
| CN101495838A (en) * | 2005-08-05 | 2009-07-29 | 奥本大学 | Reversible electrochemical sensors for polysions |
| US8603803B2 (en) * | 2006-12-28 | 2013-12-10 | Intel Corporation | Solid phase electrochemical synthesis with controlled product cleavage |
| CN103945931A (en) * | 2011-09-26 | 2014-07-23 | 基因技术股份公司 | High efficiency, small volume nucleic acid synthesis |
| CN103472123A (en) * | 2013-09-30 | 2013-12-25 | 湖南师范大学 | In-situ anode dissolving-out volt-ampere analytical method based on metal marking and biology affinity |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN112662660A (en) * | 2020-12-11 | 2021-04-16 | 复旦大学 | Electrode array device for gene sequence synthesis and control method thereof |
| CN112662660B (en) * | 2020-12-11 | 2022-09-16 | 复旦大学 | Electrode array device for gene sequence synthesis and control method thereof |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| ES2770055T3 (en) | Sequencing without enzyme or amplification | |
| KR102476709B1 (en) | Chemical compositions and methods of using same | |
| US10793898B2 (en) | Nano-sensors for nucleic acid detection and discrimination | |
| CN104379766B (en) | The dynamics of nucleic acid library excludes amplification | |
| Egeland et al. | Electrochemically directed synthesis of oligonucleotides for DNA microarray fabrication | |
| US8715932B2 (en) | Nucleic acid sequencing | |
| JP2015528282A (en) | Methods and kits for nucleic acid sequencing | |
| US7115364B1 (en) | Arrays of nucleic acid probes on biological chips | |
| CN104039438A (en) | Treatment for stabilizing nucleic acid arrays | |
| JP2023525993A (en) | Equalization-based image processing and spatial crosstalk attenuator | |
| TWI592493B (en) | Integrated photonic electronic sensor arrays for nucleic acid sequencing | |
| US20140083871A1 (en) | Device and method for detecting redox reactions in solution | |
| JP2020519254A (en) | System and method for identifying and distinguishing genetic samples | |
| EP3411496A1 (en) | Molecular identification with sub-nanometer localization accuracy | |
| US9222908B2 (en) | Device and method for detecting redox reactions in solution | |
| CN106799196A (en) | DNA fabricated in situ semiconductor chip and its control method | |
| CN108130273B (en) | Detection substrate, manufacturing method thereof and method for detecting nucleic acid | |
| CN106802316A (en) | Electrochemical chip and DNA in-situ synthetic methods for DNA fabricated in situ | |
| EP3130682B1 (en) | Methods for generating polymer arrays | |
| CN101963762A (en) | Preparation device for synthesizing gene chip in situ | |
| JP2006258469A (en) | Substrate for forming nucleic acid probe | |
| Aoki et al. | Electrochemical sensor array chips for multiple gene detection | |
| 김효기 | HIGH-THROUGHPUT RETRIEVAL OF MOLECULAR CLONES FOR POLYNUCLEOTIDE SYNTHESIS |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| WD01 | Invention patent application deemed withdrawn after publication |
Application publication date: 20170606 |
|
| WD01 | Invention patent application deemed withdrawn after publication |