CN116837075A - Nucleic acid detection device and method based on solid phase carrier - Google Patents
Nucleic acid detection device and method based on solid phase carrier Download PDFInfo
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- CN116837075A CN116837075A CN202310653937.8A CN202310653937A CN116837075A CN 116837075 A CN116837075 A CN 116837075A CN 202310653937 A CN202310653937 A CN 202310653937A CN 116837075 A CN116837075 A CN 116837075A
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- 239000007790 solid phase Substances 0.000 title claims abstract description 85
- 150000007523 nucleic acids Chemical class 0.000 title claims abstract description 47
- 108020004707 nucleic acids Proteins 0.000 title claims abstract description 42
- 102000039446 nucleic acids Human genes 0.000 title claims abstract description 42
- 238000000034 method Methods 0.000 title claims abstract description 37
- 238000001514 detection method Methods 0.000 title claims abstract description 29
- 239000000523 sample Substances 0.000 claims abstract description 113
- 230000003321 amplification Effects 0.000 claims abstract description 56
- 238000003199 nucleic acid amplification method Methods 0.000 claims abstract description 56
- 239000011324 bead Substances 0.000 claims abstract description 21
- PCHJSUWPFVWCPO-UHFFFAOYSA-N gold Chemical compound [Au] PCHJSUWPFVWCPO-UHFFFAOYSA-N 0.000 claims abstract description 19
- 239000010931 gold Substances 0.000 claims abstract description 18
- 229910052737 gold Inorganic materials 0.000 claims abstract description 18
- 239000002105 nanoparticle Substances 0.000 claims abstract description 17
- 238000006243 chemical reaction Methods 0.000 claims abstract description 16
- 125000000524 functional group Chemical group 0.000 claims abstract description 13
- 238000012360 testing method Methods 0.000 claims abstract description 12
- 239000012528 membrane Substances 0.000 claims abstract description 10
- 239000004005 microsphere Substances 0.000 claims abstract description 7
- 239000002077 nanosphere Substances 0.000 claims abstract description 7
- 239000007788 liquid Substances 0.000 claims description 16
- 238000004140 cleaning Methods 0.000 claims description 15
- 239000007787 solid Substances 0.000 claims description 11
- YBJHBAHKTGYVGT-ZKWXMUAHSA-N (+)-Biotin Chemical group N1C(=O)N[C@@H]2[C@H](CCCCC(=O)O)SC[C@@H]21 YBJHBAHKTGYVGT-ZKWXMUAHSA-N 0.000 claims description 10
- 239000000969 carrier Substances 0.000 claims description 10
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- 230000009089 cytolysis Effects 0.000 claims description 9
- 108010090804 Streptavidin Proteins 0.000 claims description 6
- 239000011616 biotin Chemical group 0.000 claims description 5
- 229960002685 biotin Drugs 0.000 claims description 5
- 235000020958 biotin Nutrition 0.000 claims description 5
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- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 4
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- -1 amino, carboxyl Chemical group 0.000 claims description 3
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 3
- 238000007397 LAMP assay Methods 0.000 description 13
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- 125000003277 amino group Chemical group 0.000 description 1
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Classifications
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- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
- C12Q1/00—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions
- C12Q1/68—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving nucleic acids
- C12Q1/6813—Hybridisation assays
- C12Q1/6834—Enzymatic or biochemical coupling of nucleic acids to a solid phase
Abstract
The invention discloses a nucleic acid detection device and a method based on a solid phase carrier, comprising a plurality of capture probes, an immobilization probe and the solid phase carrier; the immobilized probes are immobilized on the solid phase carrier through reactions with various functional groups or biomolecules modified on the surface of the solid phase carrier, the plurality of capture probes are symmetrically arranged on two sides of the amplification region in pairs, one part of the sequences of the capture probes are hybridized with the target sequences, and the other part of the common base sequences of the capture probes are hybridized with the immobilized probes so as to capture and enrich the targets on the solid phase carrier; wherein the solid phase carrier comprises magnetic beads, gold nanoparticles, various microspheres, nanospheres, a filter membrane and a chromatographic test strip. The capture probe is combined with the solid-phase carrier modified solid-phase probe, so that the capture probe has stronger flexibility, is easier to combine with a target in the capture process, has higher capture efficiency, and has better consistency when the same fixed probe is combined with the solid-phase carrier.
Description
Technical Field
The invention relates to the technical field of nucleic acid extraction, in particular to a nucleic acid detection device and method based on a solid phase carrier.
Background
The nucleic acid amplification technology is widely applied to the fields of screening of pathogenic microorganisms, biochemical analysis, disease diagnosis and the like, and the real-time fluorescent quantitative polymerase chain reaction (qPCR) is used as a gold standard for detecting the pathogenic microorganisms and diagnosing the disease in most laboratories due to high sensitivity and specificity. However, qPCR still has difficulty avoiding misdiagnosis when we handle low concentration samples. Misdiagnosis is generally due to the limited total copy number after elution of nucleic acid extraction and the limited detection sensitivity of the amplification method. In commercial kit and platform based nucleic acid extraction methods, we typically process samples of hundreds of microliters or even less in volume, and only a few of the extracted nucleic acids (typically < 20L) eventually participate in the amplification reaction. And the usual nucleic acid extraction method extracts total RNA or DNA in the sample, which is liable to cause false positive results in amplification. Furthermore, nucleic acid extraction often requires precise experimental conditions and is performed by a skilled artisan, making qPCR difficult to use in resource-starved areas or in laboratories with poor conditions. Although some laboratories have developed strategies for detecting or amplifying nucleic acids without an extraction step, they mostly sacrifice sensitivity to some extent.
Disclosure of Invention
Aiming at the problems existing in the prior art, the invention aims to provide a nucleic acid detection device and a method based on a solid phase carrier, which can solve the problems of complex and time-consuming nucleic acid extraction operation, low nucleic acid detection sensitivity, poor specificity and the like in the existing nucleic acid detection scheme.
In order to achieve the above object, the present invention provides a solid-phase carrier-based nucleic acid detection device comprising a plurality of capture probes, an immobilization probe, and a solid-phase carrier; the immobilized probes are immobilized on the solid phase carrier through reactions with various functional groups or biomolecules modified on the surface of the solid phase carrier, the plurality of capture probes are symmetrically arranged on two sides of the amplification region in pairs, one part of the sequences of the capture probes are hybridized with the target sequences, and the other part of the common base sequences of the capture probes are hybridized with the immobilized probes so as to capture and enrich the targets on the solid phase carrier; wherein the solid phase carrier comprises magnetic beads, gold nanoparticles, various microspheres, nanospheres, a filter membrane and a chromatographic test strip.
Further, the various functional groups modified on the surface of the solid phase carrier comprise amino groups, carboxyl groups or streptavidin.
Further, the surface of the immobilized probe is modified with carboxyl, amino or biotin.
Further, the capture probe sequence is as follows:
the invention also provides a nucleic acid specific capturing and enriching method based on a solid phase carrier, which is characterized in that the nucleic acid detecting device according to any one of claims 1-3 is utilized, and the nucleic acid detecting method comprises the following steps:
modifying various functional groups on the surface of the solid phase carrier;
modifying biomolecules on the surface of the immobilized probes;
reacting various functional groups modified on the surface of the solid phase carrier with biomolecules modified on the surface of the immobilized probe to immobilize the immobilized probe on the solid phase carrier;
hybridizing a part of the sequence of the capture probe with the target sequence, and hybridizing the other part of the common sequence of the capture probe with the fixed probe to enrich target capture on a solid-phase carrier;
after incubation for 20 minutes at a certain temperature, target lysis, capture and enrichment was completed.
Further, the target sequence is RNA or DNA.
Further, capturing and enriching is performed directly when the target sequence is RNA.
Further, when the target sequence is DNA, the double strand of DNA is first unwound and then captured and enriched.
Further, the method further comprises the following steps:
and (3) cleaning the supernatant by adopting corresponding cleaning modes according to different solid-phase carriers, and cleaning the solid-phase carriers by using the cleaning liquid.
Further, the method further comprises the following steps:
after washing the solid phase carrier, placing the solid phase carrier in a nucleic acid amplification tube, heating and incubating at 60-65 ℃, and reacting for 20-30 minutes to complete LAMP amplification.
Further, when the solid phase carrier is magnetic beads, the solid phase carrier is cleaned by magnetic separation; when the solid phase carrier is gold nano particles, other microspheres or nanospheres, the solid phase carrier can be cleaned by centrifugation; when the solid phase carrier is a filter membrane, cleaning is carried out through filtration; when the solid phase carrier is a chromatographic test strip, the solid phase carrier can be washed by a chromatographic washing liquid.
According to the invention, the target nucleic acid sequence is specifically captured through the capture probe, the complex nucleic acid extraction process with complex operation is replaced, the detection specificity is improved, the target nucleic acid is enriched by using the solid phase carrier, the detection sensitivity is improved, the capturing with high efficiency can be realized by using a trace of solid phase carrier, such as magnetic beads or gold particles with microgram level, the reagent cost can be saved, meanwhile, the elution is not needed, the trace of solid phase carrier can directly participate in the amplification reaction, the loss of nucleic acid is reduced, the nucleic acid detection time is shortened, and the operation flow is simplified.
Drawings
In order to more clearly illustrate the technical solutions of the embodiments of the present invention, the drawings required for the description of the embodiments will be briefly described below, and it is apparent that the drawings in the following description are only some embodiments of the present invention, and other drawings may be obtained according to these drawings without inventive effort for a person skilled in the art.
FIG. 1 is a schematic diagram of a solid support-based nucleic acid detection apparatus according to an embodiment of the present invention;
FIG. 2 is a flow chart of a digital LAMP of droplets based on magnetic bead capture and enrichment according to an embodiment of the invention;
FIG. 3 is a visual LAMP flow chart based on gold nanoparticles and chromatographic test strips according to an embodiment of the invention.
Detailed Description
For the purpose of making the objects, technical solutions and advantages of the present invention more apparent, the embodiments of the present invention will be described in further detail with reference to the accompanying drawings.
As shown in FIG. 1, a solid support-based nucleic acid detection device according to an embodiment of the present invention includes a plurality of capture probes, an immobilization probe, and a solid support; the immobilized probes are immobilized on the solid phase carrier through reactions with various functional groups or biomolecules modified on the surface of the solid phase carrier, the plurality of capture probes are symmetrically arranged on two sides of the amplification region in pairs, one part of the sequences of the capture probes are hybridized with the target sequences, and the other part of the common base sequences of the capture probes are hybridized with the immobilized probes so as to capture and enrich the targets on the solid phase carrier; all capture probes have a section of the same base sequence near the 3' end, and the sequence of the capture probes is complementary to the immobilized probes and can be hybridized with the immobilized probes; wherein the solid phase carrier comprises magnetic beads, gold nanoparticles, various microspheres, nanospheres, a filter membrane and a chromatographic test strip. The specific capture probes are designed on two sides close to the amplification area, but do not cover the amplification area, and the conditions of the number, concentration, capture temperature and the like of the capture probes are required to be optimized aiming at different targets to be detected, different amplification areas and amplification methods, and the conditions of strong specificity and high sensitivity are the optimal conditions. The paired placement of capture probes on both sides of the amplified region in this example has the following effects:
1) The target RNA is easy to degrade or break in the process of splitting and capturing, capture probes are designed on two sides of the amplification area, after the capture probes are hybridized with the target, a double-chain structure is formed more stably, and the nucleic acid fragments which are finally participated in amplification can be reserved to the greatest extent, so that the detection sensitivity is improved; 2) In the hybridization process, the area covered by the capture probe is close to or very close to the area, so that base stacking force can be formed, the hybridization reaction is facilitated, and the capture efficiency of target RNA can be improved; 3) The capture probes are designed on two sides of the amplification region, do not cover the amplification region, and do not perform hybridization reaction in the capture process in the amplification region, so that the capture probes do not compete with the primer sequence in the amplification process, and the hybridization of the primer in the amplification process is facilitated.
After capturing the target by the existing specific probe based on the solid phase carrier, the target is required to be eluted by non-nuclease water or buffer solution and added into an amplification system to participate in the amplification reaction, however, in the elution process, often tens of microliters to hundreds of microliters of liquid is introduced, and finally, the volume of the target participating in the amplification reaction is only a few microliters, so that only a part of the target participates in the amplification, thereby influencing the detection sensitivity. In the detection device of this embodiment, the solid phase carriers such as magnetic beads and gold nanoparticles are only several hundred nanograms to several micrograms, and the magnetic beads or gold nanoparticles can be directly added into the amplification system without elution (without affecting amplification and fluorescence signal acquisition), so that the loss of targets is avoided, and the sensitivity of detection is improved. The amount of the solid phase carriers such as magnetic beads and the like used in the prior art is usually hundreds of micrograms, so that a large amount of magnetic beads are added into an amplification system to influence amplification reaction and acquisition of fluorescent signals after amplification, the invention can use the small amount of solid phase carriers (such as magnetic beads or gold nanoparticles and the like) to realize high-efficiency capture of target RNA/DNA, and the capture efficiency can be improved due to the design of capture probes and the specific design of the immobilized probes on the surface of the solid phase carriers.
In one embodiment of the present invention, the various functional groups modified on the surface of the solid support include amino, carboxyl or streptavidin.
In one embodiment of the present invention, the immobilized probe surface is modified with carboxyl, amino or biotin.
In one embodiment of the invention, the capture probe sequence is as follows:
in this embodiment, a total of 16 capture probes of 8 pairs of probes are symmetrically disposed at two sides of the amplification region, and it should be noted that the number of capture probes is not limited to this, and the number, concentration, capture temperature, and other conditions of the capture probes can be optimized for different targets to be detected, different amplification regions, and amplification methods. For the same target, the combination of capture probes with strong nucleic acid detection specificity and high sensitivity and the capture and enrichment condition with optimal capture temperature generally increase and decrease the number of the capture probes in pairs, and the symmetrical positions before and after the amplified region are a pair of probes, for example, probes 1 and 9 in fig. 1 are called a pair of probes. The capture probes are usually designed next to the amplified region of DNA or RNA, and several pairs of capture probes are designed on both sides of the amplified region, the difference in Tm values of all the capture probes is controlled to be as low as 5℃or less, and each capture probe contains a common base sequence for hybridization with the immobilized probe on the solid support.
The invention also provides a nucleic acid detection method based on the solid phase carrier, which comprises the following steps of:
modifying various functional groups on the surface of the solid phase carrier;
modifying biomolecules on the surface of the immobilized probes;
reacting various functional groups modified on the surface of the solid phase carrier with biomolecules modified on the surface of the immobilized probe to immobilize the immobilized probe on the solid phase carrier;
hybridizing a part of the sequence of the capture probe with the target sequence, and hybridizing the other part of the common base sequence of the capture probe with the immobilized probe to capture and enrich the target on the solid-phase carrier; after the capture reaction is finished, the targets are enriched on the surface of the solid phase carrier by methods such as magnetic separation, centrifugation or filtration, incubation and the like, and 50 mu L-50mL of samples can be processed by the method. After enrichment, the non-specific nucleic acid sequences and impurities, including some nucleic acid amplification inhibitors, etc., can be removed by washing with a buffer system. The cleaned complex of the solid phase carrier and the target nucleic acid sequence can be directly added into an amplification system to participate in amplification reaction, or the nucleic acid can be heated and thermally spun, and then the supernatant is taken out for amplification;
after incubation for 20 minutes at a certain temperature, target lysis, capture and enrichment was completed. The capturing and the cracking can be carried out simultaneously, and the mixed system with the cracking function and the capturing function can be obtained through optimization, so that the cracking of the sample and the capturing of the nucleic acid can be synchronously completed, and the detection time is further shortened.
In one embodiment of the invention, the target sequence is RNA or DNA. Capturing and enriching are directly performed when the target sequence is RNA. When the target sequence is DNA, the double strand of the DNA is firstly unwound and then captured and enriched.
In an embodiment of the present invention, the method further comprises:
and (3) cleaning the supernatant by adopting corresponding cleaning modes according to different solid-phase carriers, and cleaning the solid-phase carriers by using the cleaning liquid. For example, washing by magnetic separation when the solid support is a magnetic bead; when the solid phase carrier is gold nano particles, other microspheres or nanospheres, the solid phase carrier can be cleaned by centrifugation; when the solid phase carrier is a filter membrane, cleaning is carried out through filtration; when the solid phase carrier is a chromatographic test strip, the solid phase carrier can be cleaned by a chromatographic washing liquid
In an embodiment of the present invention, the method further comprises:
after washing the solid phase carrier, placing the solid phase carrier in a nucleic acid amplification tube, heating and incubating at 60-65 ℃, and reacting for 20-30 minutes to complete LAMP amplification. The nucleic acid detection method may be PCR, RT-PCR, isothermal amplification methods such as: LAMP, RCA, RPA, RAA, non-amplification methods such as CRISPR-based detection methods, various types of digital amplification methods such as droplet digital PCR, droplet digital LAMP, droplet digital CRIPSR, and the like.
In order to make the present invention more clearly understood by those skilled in the art, the following describes the specific flow of the method of the present invention by way of two specific examples.
Embodiment case 1:
referring to fig. 1 and 2, for RNA target sequences, the sample to be tested is mixed without any pretreatment with a capture and lysis system comprising, in addition to the usual lysis system components, an optimized concentration of capture probes and magnetic beads anchored with immobilized probes. Streptavidin is modified on the surface of the magnetic beads, and the immobilized probes are anchored by reacting with the biotin modified on the immobilized probes. After the target, the magnetic beads, the capture probes and the lysis system are mixed, incubating for 20 minutes under the condition of optimal capture temperature, and then the lysis, capture and enrichment of the target can be completed. The supernatant is then separated magnetically and the beads are washed twice with a wash solution to remove excess probes, impurities in the sample and non-specific nucleic acid sequences.
After the capture and enrichment of the target sequence are completed, the magnetic beads connected with the target sequence are mixed with a loop-mediated isothermal amplification (LAMP) system to form a water phase, and an oil phase is added into an oil phase channel of a liquid drop generating chip, and the oil phase and the water phase are continuously introduced under the condition of a certain flow rate ratio, so that water-in-oil liquid drops can be generated. The relevant primer sequences for LAMP detection of the novel coronavirus N gene are as follows:
the primer sequences used above are only illustrative, and the present invention is not limited thereto.
Dispersing the generated liquid drops into a collecting chamber, heating and incubating the collecting chamber at 60-65 ℃, reacting for 20-30 minutes, completing LAMP amplification, photographing by a fluorescence microscope, and analyzing the result. The liquid drops containing more than 1 copy of target sequences have LAMP amplified products, fluoresce, are positive liquid drops, the liquid drops without target sequences do not have amplified products, do not fluoresce, are negative liquid drops, and count the number of the positive liquid drops, so that quantitative detection results can be obtained, and quantitative detection of the target sequences is realized.
Embodiment case 2:
referring to fig. 3, for an RNA target sequence, a sample to be tested is mixed with a capture and cleavage system comprising, in addition to conventional cleavage system components, an optimized capture probe of a certain concentration and gold nanoparticles with immobilized probes modified by thiol groups. The 5 'modified sulfhydryl of the immobilized probe is used for reacting with gold nanoparticles, and the 3' modified biotin of the immobilized probe is used for reacting with streptavidin coated on the chromatographic test strip. After the target, the capture probe, the gold nanoparticle and the lysis system are mixed, incubating for 20 minutes under the optimal capture condition, and then the lysis, capture and enrichment of the target can be completed. Adding the mixed system to a sample pad of a chromatographic test strip, carrying out chromatography on the mixed system on a nitrocellulose membrane (NC membrane), capturing gold nanoparticles with target sequences, enriching under the coating condition through the reaction of biotin on an immobilized probe and streptavidin coated on the NC membrane, adding a washing liquid on the chromatographic test strip for chromatography after the reaction is finished, and removing residual capturing and cracking systems, impurities and the like.
After the experiment is finished, shearing strips enriched with gold nanoparticles and target complexes on a chromatographic test strip, placing the strips in a nucleic acid amplification tube, adding a visual LAMP amplification system, heating and incubating at 60-65 ℃ for 20-30 minutes, and finishing LAMP amplification, wherein the color change of the amplification system is observed by naked eyes, and if the color change is yellow or orange, the sample to be detected is positive; if the color is kept unchanged, the sample to be tested is negative, so that the sample can be qualitatively detected.
In summary, compared with the prior art, the invention has the following advantages:
(1) The capture probe is combined with the solid-phase probe modified on the surface of the magnetic bead, so that the capture probe has stronger flexibility, is easier to combine with a target in the capture process, has higher capture efficiency, and has better consistency when the same fixed probe is combined with a solid-phase carrier.
(2) The capture probe is close to the amplification reaction area but does not cover the amplification area, so that degradation and loss of RNA in the process of cracking and capturing can be reduced, and competition for primer combination in the process of amplification can be avoided, thereby being more beneficial to amplification of a target amplification area;
(3) The invention is based on the specific design of the capture probe and the immobilized probe, so that the amount of the introduced solid phase carrier is from hundreds of nanograms to micrograms, the amount of the solid phase carrier is very small, and the magnetic beads or the gold nanoparticles can be directly added into an amplification system without elution to participate in amplification, thereby avoiding the loss of nucleic acid.
The foregoing description of the preferred embodiments of the invention is not intended to limit the invention to the precise form disclosed, and any such modifications, equivalents, and alternatives falling within the spirit and scope of the invention are intended to be included within the scope of the invention.
Claims (10)
1. A nucleic acid detection device based on a solid support, comprising a plurality of capture probes, an immobilization probe, and a solid support; the immobilized probes are immobilized on the solid phase carrier through reactions with various functional groups or biomolecules modified on the surface of the solid phase carrier, the plurality of capture probes are symmetrically arranged on two sides of the amplification region in pairs, one part of the sequences of the capture probes are hybridized with the target sequences, and the other part of the common base sequences of the capture probes are hybridized with the immobilized probes so as to capture and enrich the targets on the solid phase carrier; wherein the solid phase carrier comprises magnetic beads, gold nanoparticles, various microspheres, nanospheres, a filter membrane and a chromatographic test strip.
2. The nucleic acid-specific capture and enrichment device of claim 1, wherein the various functional groups modified on the surface of the solid support comprise amino, carboxyl, or streptavidin.
3. The nucleic acid-specific capture and enrichment device of claim 2, wherein the immobilized probe surface is modified with carboxyl, amino, or biotin.
4. A nucleic acid detection method based on a solid support, characterized in that the nucleic acid detection method comprises the steps of:
modifying various functional groups on the surface of the solid phase carrier;
modifying biomolecules on the surface of the immobilized probes;
reacting various functional groups modified on the surface of the solid phase carrier with biomolecules modified on the surface of the immobilized probe to immobilize the immobilized probe on the solid phase carrier;
hybridizing a part of the sequence of the capture probe with the target sequence, and hybridizing the other part of the common sequence of the capture probe with the fixed probe to enrich target capture on a solid-phase carrier;
after incubation for 20 minutes at a certain temperature, target lysis, capture and enrichment was completed.
5. The method of claim 4, wherein the target sequence is RNA or DNA.
6. The method of claim 5, wherein capturing and enriching is performed directly when the target sequence is RNA.
7. The method of claim 5, wherein when the target sequence is DNA, the double strand of DNA is first unwound and then captured and enriched.
8. The method as recited in claim 5, further comprising:
and (3) cleaning the supernatant by adopting corresponding cleaning modes according to different solid-phase carriers, and cleaning the solid-phase carriers by using the cleaning liquid.
9. The method as recited in claim 8, further comprising:
after washing the solid phase carrier, placing the solid phase carrier in a nucleic acid amplification tube, heating and incubating at 60-65 ℃, and reacting for 20-30 minutes to complete LAMP amplification.
10. The method of claim 8, wherein the washing is performed by magnetic separation when the solid support is a magnetic bead; when the solid phase carrier is gold nano particles, other microspheres or nanospheres, the solid phase carrier can be cleaned by centrifugation; when the solid phase carrier is a filter membrane, cleaning is carried out through filtration; when the solid phase carrier is a chromatographic test strip, the solid phase carrier can be washed by a chromatographic washing liquid.
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| CN202310653937.8A CN116837075A (en) | 2023-06-05 | 2023-06-05 | Nucleic acid detection device and method based on solid phase carrier |
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