CN107354207A - Solution hybridization capture agent box, washing reagent box and its application based on double-chain probe - Google Patents
Solution hybridization capture agent box, washing reagent box and its application based on double-chain probe Download PDFInfo
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Abstract
The invention discloses a kind of gene order-checking Library hybridization capture agent box, washing reagent box and they solution hybridization capture in application.The capture agent box includes 2 × strength solution and 100% deionized formamide, wherein, 2 × the strength solution includes 100 150mM sodium dihydrogen phosphate, 4 × sodium citrate buffer solution, 1 3mM ethylenediamine tetra-acetic acid, 2 × Denhardt solution, 2 5mg/ml Carrier RNA and 15 20w/w% dextran sulfate, wherein, 4 × the sodium citrate solution includes 0.6M sodium chloride, 0.06M sodium citrates, pH7.0；And 2 × Denhardt solution includes 0.04% ficoll 400,0.04% polyvinylpyrrolidone and 0.04% bovine serum albumin.
Description
Technical field
The invention belongs to biology field, is related to gene order-checking Library hybridization capture agent box, washing reagent box
And their applications in solution hybridization capture.
Background technology
The new-generation sequencing that has been born early 20th century technology (Next Generation Sequencing, NGS), this technology
Appearance bring the progress advanced by leaps and bounds for DNA sequencing technology field.Compared with generation sequencing technologies, two generation sequencing technologies tool
There is the technical characterstic of high flux, high accuracy, hundreds of millions of DNA fragmentations can be sequenced simultaneously.With traditional Sanger
Method sequencing substantially reduces compared to NGS sequencings cost.But genome sequencing cost is still higher, and much researchs are applied and are not required to
Genome sequencing is wanted, and the demand being sequenced for the target area of one or more samples is more urgent, therefore to target area
Targetedly sequence measurement can significantly decrease sequencing cost in domain, while can also shorten sequencing time and analysis of biological information
Cycle.The appearance of target sequence capture technique, meets the demand.Target sequence capture sequencing is for known specific base
Because being sequenced after group region design probe capture, uninterested DNA fragmentation can be by greatest extent in enrichment process is targetted
Removal so that result caused by sequencing focuses primarily upon target area interested.Currently used sequence capturing method
Have：PCR methods, molecular inversion probes method (MolecuLar insersion probe, MIP) and hybrid capture.PCR methods have
High sensitivity, high specific and it is reproducible the advantages that, but this method can not be easy to expand target area, be adapted to catch
The region of some very littles is obtained, and subregion amplification is difficult, for the relatively low somatic mutation detection sensitivity of the frequency of mutation not
The problems such as enough, does not have good solution.Molecular inversion probes method has sample processing early stage is simple, sample requirements are small etc.
Advantage, but its molecular probe synthesis cost is higher, homogeneity is poor, it is difficult to which the genome sequence larger to some regions is carried out
Capture.Hybrid capture carries biotinylated probe specific hybrid mode by target DNA fragments and by target sequence
Capture and separate.Using relatively broad in two generation microarray datasets, especially solution hybridization catching method exists this technology
There is exclusive advantage in target area capture technique field.Solution hybridization capture technique can overcome above-mentioned PCR methods and molecule to fall
The problem of putting sonde method, there is more preferable capture rate, less Preference, higher detection sensitivity, easier operation
The advantages that with suitable cost.
Efficient capture rate and high accuracy depend primarily on three aspects in solution hybridization capture technique：1. probe
Accuracy and specificity；2. hybridization buffer environment and hybridization conditions；3. lavation buffer solution environment and wash conditions after hybridization.
The biological Avidin label probe of high accuracy and high specific is the guarantee of high hybridization accuracy, and the existing probe in this area closes
The level can be reached into technology, such as Integrated Device Technology, Inc.Probe synthetic technology.And find a kind of height
Hybridization buffer, hybridization conditions and the lavation buffer solution and washing methods of effect are particularly important, and this link is to effectively improve
Hybridization efficiency, capture accuracy is improved, simplify experiment flow and reduce the main bottleneck and rate-limiting step of cost.
Therefore, based on above achievement in research and technical characterstic, a kind of efficient, liquid that the degree of accuracy is high, inexpensive is developed
Phase hybrid capture reagent and method are more urgent, to meet targeting to be sequenced growing requirement.
The content of the invention
The present invention relates to the new compositions, related kit and hybridisation wash side for duplex nucleic acid hybridization and washing
Method.These compositions and method compared with conventional procedure, can faster, more efficient, capture effect preferably complete genomic DNA
Targeting regions enrichment.
One aspect of the present invention is to provide a kind of gene order-checking Library hybridization capture agent box, it includes 2 × and it is dense
Solution and 100% deionized formamide are spent,
Wherein, the 2 × strength solution includes 100-150mM sodium dihydrogen phosphate, 4 × sodium citrate buffer solution, 1-3mM
Ethylenediamine tetra-acetic acid, 2 × Denhardt solution, 2-5mg/ml Carrier RNA and 15-20w/w% dextran sulfate,
Wherein, the 4 × sodium citrate solution includes 0.6M sodium chloride, 0.06M sodium citrates, pH7.0；And
2 × Denhardt solution includes 0.04% ficoll 400,0.04% polyvinylpyrrolidone and 0.04%
Bovine serum albumin.
Preferably, the 4 × sodium citrate solution dilutes 5 times of preparations by 20 × sodium citrate solution and obtained, described 20 ×
Sodium citrate solution includes 3M sodium chloride, 0.3M sodium citrates, pH7.0；And
2 × Denhardt solution dilutes 25 times of preparations by 50 × Denhardt solution and obtained, described 50 ×
Denhardt solution includes 1% ficoll 400,1% polyvinylpyrrolidone and 1% bovine serum albumin.
In one preferred embodiment, the 2 × strength solution includes 100mM sodium dihydrogen phosphate, 4 × citric acid
Sodium buffer solution, 2mM ethylenediamine tetra-acetic acid, 2 × Denhardt solution, 2mg/ml Carrier RNA and 20w/w% sulfuric acid
Glucan.
Another aspect of the present invention provides a kind of application method of said gene group sequencing library hybrid capture kit, its
Comprise the following steps：
2 × the strength solution is mixed with 100% deionized formamide and probe solution according to following condition：
2 × the strength solution is diluted one times in final solution, and
Concentration of the deionized formamide in final solution is 20-50v/v%.
Another further aspect, the invention provides a kind of gene order-checking Library hybridization to capture solution, and it passes through above-mentioned user
Method obtains.
Another aspect, the present invention provide the wash solution kit after a kind of capture for gene order-checking Library hybridization,
It includes following 5 kinds of lavation buffer solution components：
1) Stringent wash solutions：2 × sodium citrate buffer solution, 30%v/v% deionized formamides；
2) wash solution I：2 × sodium citrate solution, 0.1% lauryl sodium sulfate (SDS)；
3) wash solution II：2 × sodium citrate solution；
4) wash solution III：0.2 × sodium citrate solution；And
5) Streptavidin MagneSphere wash solution：10mM Tris-HCl pH 7.5-8.0,1mM EDTA and 2M
NaCl,
Wherein, the 2 × sodium citrate solution includes 0.3M sodium chloride and 0.03M sodium citrates, pH 7.0, and
0.2 × the sodium citrate solution includes 0.03M sodium chloride and 0.003M sodium citrates, pH 7.0.
Preferably, the 2 × sodium citrate solution and 0.2 × sodium citrate solution are 20 × sodium citrate solution
Dilution, the 20 × sodium citrate solution include 3M sodium chloride and 0.3M sodium citrates, pH 7.0.
Another aspect of the present invention provides a kind of gene order-checking Library hybridization kit, and it is tried comprising above-mentioned hybrid capture
Agent box and above-mentioned wash solution kit.
Genomic DNA is surveyed in probe another aspect provides said gene group sequencing library hybridization kit
Preface storehouse carries out the purposes in hybrid capture enrichment.
Another further aspect, the present invention provide a kind of solution hybridization catching method, wherein, in the process using above-mentioned hybridization
Capture agent box and/or above-mentioned wash solution kit.
Beneficial effect
Double-strandednucleic acid solution hybridization capture solution and wash solution kit provided by the invention have higher efficiency, can
To shorten hybridization time to 16h, and the commercial kit general cross time is 64-72h, therefore, can greatly shorten experiment
In the cycle, reduce cost；Wash solution has preferably elution effect, and nontarget area DNA fragmentation is greatly reduced, effectively improves
Bioaccumulation efficiency is targetted, reduces cost.
Brief description of the drawings
Fig. 1 shows the comparative result of the enrichment times of 4 target genes in three experimental groups.
Fig. 2 shows the comparative result of the enrichment times of 2 non-targeted genes in three experimental groups.
Wherein, the commodity in use kit hybridization solution of experimental group 1 and wash solution, experimental group 2 and experimental group 3 use this
Invention capture solution and wash solution kit, experiment condition is identical, evaluation self-control reagent performance.Target gene and non-targeted base
The enrichment times of cause are detected by real-time quantitative PCR (realtime-qPCR).Testing result is independent repeated trials three times
Averaging of income value ± standard error (mean ± SEM).
Embodiment
Term " 2 × strength solution " in the present invention refers to that the concentration of the solution is its working solution concentration when in use
2 times, it also is understood as needing the solution diluting one times when in use.
Embodiment of the present invention is described in detail below in conjunction with embodiment, but those skilled in the art will
It will be appreciated that in each embodiment of the present invention, in order that reader more fully understands the application and proposes many ins and outs.But
Even if it is that, without these ins and outs, the technical scheme that each claim of the application is protected can also be realized.
Denhardt ' the soluction used in the example below of the present invention are purchased from Amresco companies, Carrier
RNA is purchased from Tiangeng biochemical technology Co., Ltd, and deionized formamide liquid is purchased from Suo Laibao bio tech ltd.
Embodiment
Prepare the preparation that embodiment 1 captures solution
The solution is by sodium dihydrogen phosphate (NaH2PO4) buffer solution, sodium citrate buffer solution (SSC), ethylenediamine tetra-acetic acid
(EDTA), deionized formamide, Denhardt (Denhardt) solution, Carrier RNA and dextran sulfate are matched somebody with somebody
System forms.2 × strength solution is prepared first (is free of deionized formamide, deionized formamide liquid is individually added into
Catch
Obtain in solution), it can preserve for a long time under the conditions of -20 DEG C, specific formula is as follows：
100mM NaH2PO4
4×SSC
2mM EDTA
2 × Denhard solution
2mg/ml Carrier RNA
20w/w% dextran sulfates
PH value of solution 7.0
Capture solution includes 2 × strength solution and 100% formamide liquid, and the work of hybrid capture solution is formed after mixing
Liquid, volumetric mixture ratio is for example shown in table 1 below.
Table 1
Prepare the preparation of the wash solution kit of embodiment 2
The wash solution kit includes 5 kinds of lavation buffer solution components, can for a long time preserve under the conditions of -20 DEG C, specifically match somebody with somebody
Side is as follows：
Stringent wash solutions：2 × SSC solution, 30v/v% deionized formamides.
Wash solution I：2 × SSC solution, 0.1% lauryl sodium sulfate (SDS).
Wash solution II：2 × SSC solution.
Wash solution III：0.2 × SSC solution.
Biotin is affine magnetic bead wash solution：10mM Tris-HCl, pH 7.5；1mM EDTA；2M NaCl.
Embodiment 1 captures the application of solution and wash solution kit in hybrid capture enrichment
Specifically, whole experiment flow includes：The sample DNA extracted is broken into 200- by ultrasound first
250bp DNA fragmentation (but be not limited to ultrasonic wave and interrupt method), repaired by end, add " A " and connection procedure to connect DNA fragmentation
Upper index joints；Followed by the capture library of structure with hybridizing containing target gene region DNA fragment to be captured, capture
The DNA fragmentation of target area, the concentration effect of target area DNA fragmentation is evaluated, these DNA fragmentations are sequenced.By life
Pattern detection result is obtained after thing informatics data analysis.
1. sample genomic dna extracts and prepared by library
QIAamp DNA Blood Mini Kit reagent of the extracting method of sample genomic dna with reference to Qiagen companies
Box, people's whole blood genome sample that numbering is S1 is extracted respectively.Obtained high quality genomic DNA sample fragment is melted into
200-250bp DNA fragmentation, sample is divided into 3 parts and carries out parallel library construction experiment, then pass through end repair plus " A " and
The processes such as connection, 3 groups of DNA fragmentations are connected into 3 different index joints respectively, and (related reagent comes from KAPA Hyper Prep
Kit Illumina platforms), sample DNA library is obtained after PCR amplification purifications.The index that three samples use
Sequence is as follows：S1-1：ATCACG；S1-2：CGATGT；S1-3：TTAGGC.
2. genomic library mixing, close and dry
By the genome dna library built according to data volume allocation proportion mix, total amount 1ug, then by COT DNA,
Genome dna library mixes with closing primer according to the ratio in such as table 2 below.Wherein COT DNA are as repetitive rate in genome
Higher a part of DNA fragmentation, hybridization efficiency is favorably improved in hybridization, and the sequencing that closing primer is used for closing in library connects
Head.The above-mentioned sample mixed is evaporated for 60 DEG C in instrument is concentrated in vacuo, for subsequently hybridizing.
Table 2
3. dissolve and be denatured again：10.5 μ L capture solution is added into above-mentioned dried mixture.Experimental group 1,
Sample number is S1-1, uses Roche NimbleGen commercial kit hybridizing reagents；Experimental group 2, sample number S1-
2, use the capture solution that the preparation of embodiment 1 is prepared as above；Experimental group 3, sample number S1-3, for the repetition of experimental group 2
Experiment.The dissolving that is fully vortexed is denatured 10min after 95 DEG C.
4. hybridization：10.5 μ L mixtures being denatured are added in 4.5 μ L hybrid capture Probe Libraries, three groups of experiments make
Solution hybridization capture is carried out with identical double chain DNA probe, vortex 30s centrifuges 30s at full speed after fully dissolving mixing.Experimental group 1 in
47 DEG C of hybridization 64h, experimental group 2,3 hybridize 16h in 55 DEG C.
5. Streptavidin MagneSphere captures target area DNA library fragment：After hybridization reaction, 15 μ L samples are transferred to thing
The Bead Wash Buffer (experimental group 1) first passed through respectively in Roche NimbleGen commercial kits and above-mentioned preparation
The 100 μ L marked by streptavidin magnetic that Streptavidin MagneSphere wash solution (experimental group 2,3) washing prepared by embodiment 2 is resuspended
In pearl, experimental group 1 is incubated 45min in 47 DEG C after mixing, and experimental group 2,3 is incubated 45min in 55 DEG C, is mixed every piping and druming in 15 minutes
Once, allow the fragment of capture to be combined with magnetic bead, Specific adsorption target fragment, the fragment hybridized to is crawled out.
Experimental group 1, sample number S1-1, use Roche NimbleGen commercial kit elution reagents；Experimental group
2, sample number S1-2, use the wash solution that the preparation of embodiment 2 is prepared as above；Experimental group 3, sample number S1-3,
Tested for the repetition of experimental group 2.
6. wash nontarget area DNA fragmentation：Here elution reagent elution prepared by above-mentioned preparation embodiment 2 is mainly described
Step.
1. experimental group 1 adds the wash solution I of the Roche NimbleGen commercial kits of 100 μ L, 47 DEG C of preheatings,
Experimental group 2,3 adds wash solution I prepared by the above-mentioned preparation embodiment 2 of 100 μ L, 55 DEG C of preheatings, and magnetic levitation is abandoned after mixing
Supernatant, it is repeated once.
2. experimental group 1 adds the Stringent Wash Buffer of 200 μ L, 47 DEG C of preheatings, experimental group 2,3 adds 200 μ L
Stringent wash solutions prepared by the above-mentioned preparation embodiment 2 of 55 DEG C of preheatings, 55 DEG C of incubation 5min, magnetic levitation after mixing
Supernatant is abandoned, in triplicate, totally four times.
3. experimental group 1 adds the wash solution I of Roche NimbleGen commercial kit elution reagents, experimental group 2,3
Wash solution I prepared by the above-mentioned preparation embodiments 2 of 200 μ L, vortex 2min are added, magnetic levitation abandons supernatant.
4. the wash solution II of the addition Roche NimbleGen commercial kit elution reagents of experimental group 1, experimental group 2,
3 add wash solution II prepared by the above-mentioned preparation embodiments 2 of 200 μ L, vortex 1min, and magnetic levitation abandons supernatant.
5. experimental group 1 adds the wash solution III of Roche NimbleGen commercial kit elution reagents, experimental group
2nd, 3 wash solution III prepared by the above-mentioned preparation embodiments 2 of 200 μ L, vortex 30s are added, magnetic levitation abandons supernatant.
6. add 50 μ L PCR rank dd H2Magnetic bead is resuspended in O.
7. it is enriched with after capture：After elution magnetic bead with capture target DNA fragments, into sample LM-PCR be enriched with.LM-
PCR reaction systems (a capture sample does two pipe PCR reactions) as shown in table 3 below.
Table 3
PCR reaction conditions are：98 DEG C of pre-degeneration 45s；98 DEG C of denaturation 15s, 60 DEG C of annealing 30s, 72 DEG C of extension 30s, totally 14
Individual circulation；72 DEG C of extension 1min；4 DEG C of insulations.
After reaction, using purify magnetic bead AMPure beads purifying pcr amplification product, the sample library after being captured,
It is used for sequencing analysis after quality inspection.
EXPERIMENTAL EXAMPLE 1 carries out enrichment times measure using quantitative fluorescent PCR to target area and nontarget area
Utilize the enrichment times of target area and nontarget area before and after the measure enrichment of SYBR Green methods.Reaction system
As shown in table 4 below.
Table 4
PCR reaction conditions are：95℃10min；95 DEG C of 10s, 60 DEG C of 1min, totally 40 circulations；95 DEG C of 10s, 65 DEG C of 1min.
The Ct values of sample are measured by the signal of collection, the Ct values for measuring sample depend on the initial concentration of template DNA in reaction, Ct values
More low then template DNA initial concentration is higher, and its enrichment times can be assessed thus according to sample Ct differences change before and after enrichment.Base
More than experiment obtain three experimental groups target area and nontarget area enrichment condition as shown in drawings.Fig. 1 display experiments
4 target area enrichment times are apparently higher than 4 target area enrichment times in experimental group 1 in group 2,3, therefore make reagent by oneself
Hybrid capture efficiency is apparently higher than commercial kit.Fig. 2 shows 2 nontarget area enrichment times experiments in experimental group 2,3
Group is significantly lower than 2 nontarget area enrichment times in experimental group 1, therefore makes the elution efficiency of reagent by oneself apparently higher than commercialization
Kit, it can effectively remove the non-targeted fragment of background.
The high-flux sequence of EXPERIMENTAL EXAMPLE 2 and data analysis
High-flux sequence is carried out using two generation microarray datasets, the sequence of capture is sequenced in Illumina NextSeq 500
Platform carries out sequencing (sequencing reagent is purchased from Illumina business sequencing kit), and carrying out analysis to obtained data can
Know sequence label thereon, its corresponding sample DNA source is determined according to sequence label, compared according to target area, can obtain
Target area valid data, and then obtain the target area information of sample.Above method is obtained using two generations sequencing means
Sequencing library has carried out being sequenced and obtaining sequencing data, and relevant analysis result is as shown in table 5 below.
Data results after table 5 is sequenced
Experiment uses identical solution hybridization capture probe, and self-made hybrid reagent is assessed under identical experiment condition and is washed
Wash the effect of reagent.As a result show, all sample standard deviations achieve good sequencing capture effect, and average sequencing depth all exists
More than 15000X, and each site homogeneity is preferable, coverage rate reaches 100%.As a result show that self-control reagent experimental group is capturing
Apparently higher than commercial reagents in terms of efficiency and data validity, and hybridization time is substantially reduced to 16h, therefore the present invention carries
The reagent and method of confession can reach testing result and be better than commercial kit effect.
For the present invention, it will be understood by those skilled in the art that the respective embodiments described above are to realize the present invention
Embodiment is embodied, and appropriate change can be made on details of operation in practical operation, without departing from invention spirit and
Scope.Protection scope of the present invention is defined by the following claims, but the content also limited simultaneously comprising claim
Equivalents form, for example, those skilled in the art apparently understands, can by the thought according to the present invention and experiment
Prepared to obtain capablely 3 ×, 4 ×, 5 ×, 6 ×, the stock solution waited was also unambiguously fallen into as hybrid capture solution
In protection scope of the present invention.
Claims (8)
1. a kind of gene order-checking Library hybridization capture agent box, it includes 2 × strength solution and 100% deionization formyl
Amine,
Wherein, the 2 × strength solution includes 100-150mM sodium dihydrogen phosphate, 4 × sodium citrate buffer solution, 1-3mM second
Ethylenediamine tetraacetic acid (EDTA), 2 × Denhardt solution, 2-5mg/ml Carrier RNA and 15-20w/w% dextran sulfate,
Wherein, the 4 × sodium citrate solution includes 0.6M sodium chloride, 0.06M sodium citrates, pH7.0；And
2 × Denhardt solution includes 0.04% ficoll 400,0.04% polyvinylpyrrolidone and 0.04% ox blood
Albumin.
2. gene order-checking Library hybridization capture agent box according to claim 1, wherein, 2 × strength solution bag
Ethylenediamine tetra-acetic acid, 2 × Denhardt solution, the 2mg/ of sodium dihydrogen phosphate, 4 × sodium citrate buffer solution, 2mM containing 100mM
Ml Carrier RNA and 20w/w% dextran sulfate.
3. a kind of application method of the gene order-checking Library hybridization capture agent box described in claim 1 or 2, it includes following
Step：
2 × the strength solution is mixed with 100% deionized formamide and probe solution according to following condition：
2 × the strength solution is diluted one times in final solution, and
Concentration of the deionized formamide in final solution is 20-50v/v%.
4. a kind of application method according to claim 3 prepares obtained gene order-checking Library hybridization capture solution.
5. the wash solution kit after a kind of capture for gene order-checking Library hybridization, it includes following 5 kinds of washing buffers
Liquid component：
1) Stringent wash solutions：2 × sodium citrate buffer solution, 30%v/v% deionized formamides；
2) wash solution I：2 × sodium citrate solution, 0.1% lauryl sodium sulfate (SDS)；
3) wash solution II：2 × sodium citrate solution；
4) wash solution III：0.2 × sodium citrate solution；And
5) Streptavidin MagneSphere wash solution：10mM Tris-HCl pH 7.5-8.0,1mM EDTA and 2M NaCl, its
In, the 2 × sodium citrate solution includes 0.3M sodium chloride and 0.03M sodium citrates, pH7.0, and the 0.2 × lemon
Acid sodium solution includes 0.03M sodium chloride and 0.003M sodium citrates, pH7.0.
6. a kind of gene order-checking Library hybridization kit, it includes hybrid capture kit according to claim 1 or 2
And wash solution kit according to claim 5.
7. gene order-checking Library hybridization kit according to claim 6 enters in probe to genomic DNA sequencing library
Purposes in the enrichment of row hybrid capture.
8. a kind of solution hybridization catching method, wherein, caught in the process using hybridization according to claim 1 or 2
Obtain kit and/or wash solution kit according to claim 5.
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| CN107988317A (en) * | 2017-12-14 | 2018-05-04 | 中源协和基因科技有限公司 | A kind of buffer solution that hybrid capture is carried out to target set nucleic acid region |
| CN107988350A (en) * | 2017-12-14 | 2018-05-04 | 中源协和基因科技有限公司 | A kind of hybridization buffer for the capture of DNA sequencing Library hybridization |
| CN108690879A (en) * | 2018-05-22 | 2018-10-23 | 益善生物技术股份有限公司 | A kind of AML1-ETO fusions detection kit |
| CN114790453A (en) * | 2021-01-25 | 2022-07-26 | 上海思路迪生物医学科技有限公司 | Rapid hybridization capture kit |
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| US20040253221A1 (en) * | 2000-10-11 | 2004-12-16 | Hiroyuki Arai | Novel pla1 |
| CN101715484A (en) * | 2007-04-06 | 2010-05-26 | 协和发酵生化株式会社 | Method for producing dipeptide |
| CN104178478A (en) * | 2014-08-13 | 2014-12-03 | 邵华武 | Liquid-phase hybrid capture enriching liquor for genome DNA sequencing library and hybrid method adopting liquid-phase hybrid capture enriching liquor |
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| US20040253221A1 (en) * | 2000-10-11 | 2004-12-16 | Hiroyuki Arai | Novel pla1 |
| CN101715484A (en) * | 2007-04-06 | 2010-05-26 | 协和发酵生化株式会社 | Method for producing dipeptide |
| CN104178478A (en) * | 2014-08-13 | 2014-12-03 | 邵华武 | Liquid-phase hybrid capture enriching liquor for genome DNA sequencing library and hybrid method adopting liquid-phase hybrid capture enriching liquor |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| CN107988317A (en) * | 2017-12-14 | 2018-05-04 | 中源协和基因科技有限公司 | A kind of buffer solution that hybrid capture is carried out to target set nucleic acid region |
| CN107988350A (en) * | 2017-12-14 | 2018-05-04 | 中源协和基因科技有限公司 | A kind of hybridization buffer for the capture of DNA sequencing Library hybridization |
| CN108690879A (en) * | 2018-05-22 | 2018-10-23 | 益善生物技术股份有限公司 | A kind of AML1-ETO fusions detection kit |
| CN114790453A (en) * | 2021-01-25 | 2022-07-26 | 上海思路迪生物医学科技有限公司 | Rapid hybridization capture kit |
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| CN107354207B (en) | 2019-12-10 |
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Effective date of registration: 20191212 Address after: 116635 floor 1-2, no.9-8, Jinqi Road, advanced equipment manufacturing park, Dalian Economic and Technological Development Zone, Liaoning Province Patentee after: SHUANGDI, INC. Address before: 116635 Liaoning city of Dalian Province Economic and Technological Development Zone, advanced equipment manufacturing industry Park Jin seven road No. 9-2 Patentee before: DALIAN GENTALKER BIOTECHNOLOGY CO., LTD. |