CN111235224B - Accurate biomolecule modification method and device based on magnetophoresis separation - Google Patents
Accurate biomolecule modification method and device based on magnetophoresis separation Download PDFInfo
- Publication number
- CN111235224B CN111235224B CN202010039072.2A CN202010039072A CN111235224B CN 111235224 B CN111235224 B CN 111235224B CN 202010039072 A CN202010039072 A CN 202010039072A CN 111235224 B CN111235224 B CN 111235224B
- Authority
- CN
- China
- Prior art keywords
- magnetic beads
- separation
- biomolecules
- glass tube
- glass
- 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.)
- Active
Links
Images
Classifications
-
- 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
- C12Q1/6806—Preparing nucleic acids for analysis, e.g. for polymerase chain reaction [PCR] assay
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07J—STEROIDS
- C07J17/00—Normal steroids containing carbon, hydrogen, halogen or oxygen, having an oxygen-containing hetero ring not condensed with the cyclopenta(a)hydrophenanthrene skeleton
- C07J17/005—Glycosides
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/195—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from bacteria
- C07K14/36—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from bacteria from Actinomyces; from Streptomyces (G)
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- General Health & Medical Sciences (AREA)
- Analytical Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Genetics & Genomics (AREA)
- Zoology (AREA)
- Molecular Biology (AREA)
- Biochemistry (AREA)
- Wood Science & Technology (AREA)
- Biophysics (AREA)
- Physics & Mathematics (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Biotechnology (AREA)
- Immunology (AREA)
- Microbiology (AREA)
- Gastroenterology & Hepatology (AREA)
- Medicinal Chemistry (AREA)
- Bioinformatics & Cheminformatics (AREA)
- General Engineering & Computer Science (AREA)
- Apparatus Associated With Microorganisms And Enzymes (AREA)
- Measuring Or Testing Involving Enzymes Or Micro-Organisms (AREA)
Abstract
The invention provides a precise biomolecule modification method based on magnetophoresis separation, which comprises the following steps: (1) Providing a glass nanopore sensor, wherein the glass nanopore sensor comprises a glass tube, a metal conducting layer is deposited on the glass tube, and the glass nanopore sensor is connected with a power supply; (2) Providing a separation template, wherein the separation template is provided with at least one groove; (3) Uniformly distributing magnetic beads on a separation template, and independently placing one magnetic bead on each groove of the separation template; (4) Providing a solution containing biomolecules, loading the solution into a glass tube of the glass nanopore sensor, conducting a circuit, stopping applying a voltage when the biomolecules pass through the glass tube to generate a blocking current signal, combining the single biomolecules to the surfaces of the magnetic beads, and assembling the next magnetic beads in the same way to obtain the magnetic beads combined with the single biomolecules. The invention realizes the accurate assembly of single biomolecules and magnetic beads, and has simple assembly method and high assembly efficiency.
Description
Technical Field
The invention relates to the field of single-molecule detection, in particular to a precise biomolecule modification method based on magnetophoresis separation.
Background
The advent of molecular biology has led to a mode of research into life sciences reaching the molecular level, and direct research into basic life processes at the single molecular level has been desired. The study of DNA molecules is the basis of molecular biology studies, so single molecule manipulation also begins with the study of DNA. Currently common single molecule manipulation techniques are optical tweezers, magnetic tweezers, glass microneedles, AFM probes, stokes drag, and the like. In the control of DNA using these single molecule manipulation techniques, it is inevitable to indirectly control DNA by magnetic beads. Optical tweezers capture magnetic beads by focusing a laser beam to create an optical trap formed by radiation pressure to control DNA displacement on the beads. The magnetic tweezers control magnetic beads by using an externally applied gradient magnetic field to control DNA. The glass micro needle and the AFM probe are connected mechanically to adsorb magnetic beads to control DNA, and the glass micro needle or the AFM probe tip can be chemically modified to bind DNA to control DNA.
As described above, the single molecule manipulation technique is indirectly applied to the magnetic beads during the application process, however, in the case of streptavidin magnetic beads, all streptavidin will bind to the biotin interaction on the DNA during the DNA experiments with the modified biotin linkage, which means that several DNAs will bind to one magnetic bead, which is very disadvantageous for DNA single molecule studies. The ideal measurement of the mechanical properties of DNA molecules, the sequencing of DNA molecules and the research on the interaction between DNA and protein on the basis of the measurement require that the magnetic beads have only one DNA single strand so as to avoid the influence of other DNA molecules on the magnetic beads on experimental results. Thus, it would be of great importance to study how single biomolecules are bound to single magnetic beads.
Disclosure of Invention
The invention aims to solve the technical problems that the existing magnetic beads are difficult to combine with single biomolecules and the like, and provides a precise biomolecule modification method based on magnetophoresis separation, so that precise assembly of the single biomolecules and the magnetic beads is realized, the influence of other biomolecules on the magnetic beads on experimental results is avoided, the assembly method is simple, and the assembly efficiency is high.
The above object of the present invention is achieved by the following technical scheme:
a precise modification method of biomolecules based on magnetophoresis separation comprises the following steps:
s1, providing a glass nanopore sensor, wherein the glass nanopore sensor comprises a glass tube, a metal conducting layer is deposited on the glass tube, and the glass nanopore sensor is connected with a power supply;
s2, providing a separation template, wherein at least one groove is formed in the separation template;
s3, uniformly distributing magnetic beads on the separation template, wherein one magnetic bead is independently placed on each groove of the separation template;
and S4, providing a solution containing biomolecules, loading the solution into a glass tube of the glass nanopore sensor, conducting a circuit, stopping applying voltage when the biomolecules pass through the glass tube to generate a blocking current signal, combining the single biomolecules to the surface of the magnetic beads, and then assembling the next magnetic beads in the same way to obtain the magnetic beads combined with the single biomolecules.
There is no sequential division between step S1 and step S2.
Optionally, in the step S1, the material of the metal conductive layer includes, but is not limited to, gold, silver, aluminum, platinum, etc., and the deposition process may use physical vapor deposition, atomic layer deposition, electroplating, etc.
Optionally, in the step S1, the inner diameter of the glass tube is smaller than the diameter of the magnetic bead, so that the magnetic bead is effectively prevented from being sucked into the glass tube.
Preferably, the inner diameter of the glass tube may be 200nm to 10. Mu.m, preferably 300nm to 10. Mu.m, still preferably 400nm to 10. Mu.m, still preferably 500nm to 10. Mu.m, still preferably 800nm to 10. Mu.m, still preferably 1 μm to 10. Mu.m, still preferably 5 μm to 10. Mu.m, and the inner diameter of the glass tube is not limited to the above-mentioned range, but may be other values as long as the inner diameter of the glass tube < the diameter of the magnetic beads.
Optionally, in the step S2, the diameter of the groove is denoted as D, and the diameter of the magnetic bead is denoted as D, where D > D.
Preferably, in the step S2, D < 1.5D.
Alternatively, in the step S2, the number of grooves on the separation template may be one, two, three or more, and the number of grooves is designed according to need.
Optionally, in the step S4, the biomolecule includes an antigen molecule and/or a DNA molecule, and the antigen molecule includes but is not limited to streptavidin, digoxin, and the like.
The invention also provides a magnetic bead combined with a single biomolecule, which is modified according to the precise biomolecule modification method.
The invention also provides a biomolecule accurate modification device based on magnetophoresis separation, which comprises a separation mechanism for separating magnetic beads, wherein the separation mechanism is provided with a separation cavity and a magnet positioned outside the separation cavity, a separation template is arranged in the separation cavity, a liquid inlet of the separation cavity is communicated with a liquid supply container, a liquid outlet of the separation cavity is communicated with a collection container, and a groove for adsorbing the magnetic beads is arranged on the separation template.
Optionally, a glass nanopore sensor for delivering individual biomolecules to a surface of a magnetic bead is also included, the glass nanopore sensor comprising a glass tube having an outer surface provided with an electrode layer.
Optionally, the solution in the glass tube and the electrode layer are respectively connected to a power supply through wires, and after the voltage is applied to the power supply, the current can be conducted, so that the screening of biomolecules is realized.
Optionally, a motion platform is further included to control the motion of the glass nanopore sensor, and the motion platform controls the motion of the glass nanopore sensor in the direction of X, Y, Z.
The invention has at least the following beneficial effects:
1. realizing the accurate assembly of single biological molecule and magnetic bead. In the ideal DNA molecular mechanical property measurement, DNA molecular sequencing, DNA and protein interaction research and other DNA single molecule research based on the measurement, the assembly method provided by the invention realizes the accurate assembly of single biomolecules and magnetic beads, and avoids the influence of other biomolecules on the magnetic beads on experimental results.
2. The assembly method is simple and the assembly efficiency is high. The method for precisely assembling the single biomolecules and the magnetic beads is simple and convenient to operate, and can realize the simultaneous assembly of a plurality of magnetic beads and the biomolecules by utilizing the magnetic bead separation template, so that the assembly efficiency is improved.
Drawings
FIG. 1 is a process flow diagram of a method for precisely modifying biomolecules based on magnetophoretic separation in an embodiment of the invention.
FIG. 2 is a schematic diagram of a glass nanopore sensor required for a method for precisely modifying biomolecules based on magnetophoresis separation in an embodiment of the invention.
FIG. 3 is a schematic diagram of a separation template required for a method for precisely modifying a biomolecule based on magnetophoretic separation in an embodiment of the invention.
Fig. 4 shows a schematic diagram of a magnetophoresis separation technology presented in step 4) of a method for accurately modifying biomolecules based on magnetophoresis separation in an embodiment of the invention.
FIG. 5 shows a schematic structural diagram of the method for precisely modifying biomolecules based on magnetophoretic separation in step 4) according to an embodiment of the present invention.
FIG. 6 shows a schematic structural diagram of the method for precisely modifying biomolecules based on magnetophoretic separation in step 5) according to an embodiment of the present invention.
FIG. 7 shows a schematic diagram of detection of blocking current in step 5) of the method for accurately modifying biomolecules based on magnetophoretic separation according to an embodiment of the present invention.
Fig. 8 is a schematic diagram showing the operation of a motion platform in a method for precisely modifying biomolecules based on magnetophoresis separation according to an embodiment of the present invention.
Description of element numbers: 1. a glass nanopore sensor; 2. separating the templates; 3. magnetic beads; 4. a biological molecule; 5. a motion platform; 6. a liquid supply container; 61. a liquid inlet pipe; 7. a pump; 8. a collection container; 81. a liquid outlet pipe; 9. a magnet; 10. a glass tube; 11. an electrode layer; 12. a separation mechanism; 13. a separation chamber; 20. a groove.
Detailed Description
The invention is further illustrated in the following drawings and specific examples, which are not intended to limit the invention in any way. Unless specifically stated otherwise, the reagents, methods and apparatus employed in the present invention are those conventional in the art.
Reagents and materials used in the following examples are commercially available unless otherwise specified.
Example 1
As shown in fig. 1, the embodiment provides a method for precisely modifying a biomolecule based on magnetophoresis separation, which comprises the following steps:
s1, manufacturing a glass nanopore sensor: providing a ground glass tube, drawing a tapered nano-pore channel by using a laser melting method, and cutting a tapered nano-glass tube with a required shape, namely a glass tube 10;
s2, depositing an electrode layer 11 on the outer surface of the tapered nanopore channel to form a glass nanopore sensor 1;
s3, providing a separation template;
s4, uniformly distributing magnetic beads on a separation template by utilizing a magnetophoresis separation technology, and placing one magnetic bead on a single groove of the separation template;
s5, conveying the single biomolecules to the surface of the magnetic beads with the surface being immersed by the glass nanopore sensor. According to the number of blocking currents, accurate assembly of individual biomolecules with magnetic beads can be achieved.
The precise modification method of the biological molecule based on magnetophoresis separation of the invention is described in detail below with reference to the specific drawings.
Step S1 is firstly executed, the tapered nano-pore channel can be drawn by a laser needle drawing instrument, the inner diameter size of the capillary glass tube 10 can be 200 nm-10 mu m, and the inner diameter of the capillary glass tube is smaller than the diameter of the magnetic beads. In this embodiment, the capillary glass tube has an inner diameter of about 500nm.
Step S2 is then executed, and conductive metal materials, such as gold, silver, aluminum, platinum and the like, are deposited on the outer surface of the capillary glass tube; the deposition process may employ physical vapor deposition, atomic layer deposition, electroplating, and the like. In this embodiment, the deposition material on the outer surface of the capillary glass tube is silver, the deposition process is physical vapor deposition, and the structure of the manufactured glass nanopore sensor 1 is shown in fig. 2.
Then, step S3 is performed, where a plurality of circular grooves 20 are uniformly distributed on the separation template, and may be distributed in an array of 10×10, 20×20, etc. The diameter D of the groove ranges from 1 mu m to 10 mu m, the diameter D of the groove is larger than the diameter D of the magnetic beads and smaller than 1.5D, and the depth is 0.5D to 1.5D, so that only one magnetic bead can be accommodated in one groove. In this embodiment, six circular grooves 20 of 2×3 are uniformly distributed on the separation template 2, and the diameter D of the grooves 20 is 6 μm as shown in fig. 3.
Then, step S4 is executed, as shown in FIG. 4 and FIG. 5, magnetic beads are uniformly distributed on the separation template 2 by utilizing the magnetophoresis separation technology, one magnetic bead is placed on a single groove on the separation template, and the diameter d of the magnetic bead can be 1-10 mu m. In this example, the magnetic beads 3 have a diameter d of 5. Mu.m.
As shown in fig. 4, the separation mechanism 12 is provided with a separation cavity 13 and a magnet 9 positioned outside the separation cavity 13, the magnet 9 is positioned below the separation cavity 13, a separation template 2 is arranged in the separation cavity 13, the separation template 2 is positioned at the bottom of the separation cavity 13, so that a magnetic bead solution in the separation cavity 13 can submerge the separation template 2, a magnetic bead solution is filled in a liquid supply container 6, the liquid supply container 6 is communicated to a liquid inlet of the separation cavity 13 through a liquid inlet pipeline 61, a pump 7 is arranged on the liquid inlet pipeline 61, the pump 7 can be a microinjection pump specifically for providing power for the flow of the solution, a liquid outlet of the separation cavity 13 is communicated to a collection container 8 for collecting the solution through a liquid outlet pipeline 81, and a groove 20 for adsorbing the magnetic bead is arranged on the separation template 2.
The magnetophoresis separation method specifically comprises the following steps: and (3) conveying the magnetic bead solution by using a microinjection pump, wherein the magnetic beads are adsorbed on the separation template under the action of a gradient magnetic field when passing through the separation template, and after a certain time, the deionized water or a buffer solution is used for washing off the residual magnetic beads, so that the gradient magnetic field can be controlled by using an electromagnet.
Finally, step S5 is performed, wherein the biomolecules according to the present invention can be charged biomolecules only. When the biomolecules are negatively charged, the positive wire is connected to the silver coating, the wire is inserted over the molten silver, and the negative wire is placed in solution in the glass tube. The buffer solution of the biomolecules is PBS buffer solution. As shown in fig. 6, a single biomolecule is delivered to the surface of a magnetic bead with a surface in infiltration by a glass nanopore sensor that can be controlled to move using a nanomotor platform 5 (or nanopositioning platform, available from the company three-inch precision control instrument, ltd.). The single biomolecule may be streptavidin, digoxin and other antigenic molecules.
The voltage is 100mV, and binding of streptavidin to the magnetic beads is realized by physical and chemical methods, and one method is as follows: aldehyde groups are modified on the surfaces of the magnetic beads in advance, nucleophilic addition reaction is carried out between the aldehyde groups and amino groups of the streptavidin, and the streptavidin is introduced on the surfaces of the magnetic beads.
The biomolecules pass through the capillary glass tube to be combined with the surface of the magnetic beads under the drive of an electric field, when the biomolecules pass through the capillary glass tube, the physical occupation of the molecules generates a blocking current signal, when one biomolecule passes through the capillary glass tube to generate a blocking current signal, the application of voltage is stopped, the nanometer motion platform moves to the position of the next magnetic bead, the accurate assembly of single biomolecules is realized, fluorescent marked streptavidin is used, or DNA long chains with biotin marks are used, the streptavidin on the magnetic beads is combined with the biotin, and if the magnetic beads drag only one DNA, only one streptavidin is bound on the magnetic beads. In this example, the biomolecules used are streptavidin, and as shown in FIG. 7, the blocking current decreases when a single streptavidin passes through the glass nanopore tunnel; the nano-motion platform movement is shown in fig. 8.
In summary, the invention provides a precise biomolecule modification method based on magnetophoresis separation, which realizes precise assembly of single biomolecules and magnetic beads. In the ideal DNA molecular mechanical property measurement, DNA molecular sequencing, DNA and protein interaction research and other DNA single molecule research based on the measurement, the assembly method provided by the invention realizes the accurate assembly of single biomolecules and magnetic beads, and avoids the influence of other biomolecules on the magnetic beads on experimental results. In addition, the assembly method is simple, the assembly efficiency is high, and the magnetic bead separation template is utilized, so that a plurality of magnetic beads and biomolecules can be assembled simultaneously, and the assembly efficiency is improved.
The above examples are preferred embodiments of the present invention, but the embodiments of the present invention are not limited to the above examples, and any other changes, modifications, substitutions, combinations, and simplifications that do not depart from the spirit and principle of the present invention should be made in the equivalent manner, and the embodiments are included in the protection scope of the present invention.
Claims (9)
1. The accurate biomolecule modifying method based on magnetophoresis separation includes the following steps:
s1, providing a glass nanopore sensor, wherein the glass nanopore sensor comprises a glass tube, a metal conducting layer is deposited on the glass tube, and the glass nanopore sensor is connected with a power supply;
s2, providing a separation template, wherein at least one groove is formed in the separation template;
s3, uniformly distributing magnetic beads on the separation template, wherein one magnetic bead is independently placed on each groove of the separation template;
and S4, providing a solution containing biomolecules, loading the solution into a glass tube of the glass nanopore sensor, conducting a circuit, stopping applying voltage when the biomolecules pass through the glass tube to generate a blocking current signal, combining the single biomolecules to the surface of the magnetic beads, and then assembling the next magnetic beads in the same way to obtain the magnetic beads combined with the single biomolecules.
2. The method for precisely modifying a biological molecule according to claim 1, wherein: in the step S1, the material of the metal conductive layer is at least one selected from gold, silver, aluminum, and platinum.
3. The method for precisely modifying a biological molecule according to claim 1, wherein: in the step S1, the inner diameter of the glass tube is smaller than the diameter of the magnetic beads.
4. The method for precisely modifying a biological molecule according to claim 1, wherein: in the step S1, the inner diameter of the glass tube is 200 nm-10 μm.
5. The method for precisely modifying a biological molecule according to claim 1, wherein: in the step S2, the diameter of the groove is marked as D, and the diameter of the magnetic bead is marked as D, wherein D is larger than D.
6. The method for precisely modifying a biological molecule according to claim 5, wherein: in the step S2, D is less than 1.5D.
7. The method for precisely modifying a biological molecule according to claim 1, wherein: in the step S4, the biomolecules include antigen molecules and/or DNA molecules.
8. The method for precisely modifying a biological molecule according to claim 7, wherein: the antigen molecule comprises streptavidin and digoxin.
9. The precise biomolecule modifying device based on magnetophoresis separation is characterized by comprising a separating mechanism (12) for separating magnetic beads, wherein the separating mechanism (12) is provided with a separating cavity (13) and a magnet (9) positioned outside the separating cavity (13), a separating template (2) is arranged in the separating cavity (13), a liquid supply container (6) is communicated with a liquid inlet of the separating cavity (13), a collecting container (8) is communicated with a liquid outlet of the separating cavity (13), and a groove (20) for adsorbing the magnetic beads is formed in the separating template (2); the magnetic bead sensor further comprises a glass nanopore sensor (1) for conveying single biomolecules to the surface of the magnetic bead, wherein the glass nanopore sensor (1) comprises a glass tube (10), and an electrode layer (11) is arranged on the outer surface of the glass tube (10).
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202010039072.2A CN111235224B (en) | 2020-01-14 | 2020-01-14 | Accurate biomolecule modification method and device based on magnetophoresis separation |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202010039072.2A CN111235224B (en) | 2020-01-14 | 2020-01-14 | Accurate biomolecule modification method and device based on magnetophoresis separation |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN111235224A CN111235224A (en) | 2020-06-05 |
| CN111235224B true CN111235224B (en) | 2023-06-20 |
Family
ID=70867289
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202010039072.2A Active CN111235224B (en) | 2020-01-14 | 2020-01-14 | Accurate biomolecule modification method and device based on magnetophoresis separation |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN111235224B (en) |
Citations (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5795782A (en) * | 1995-03-17 | 1998-08-18 | President & Fellows Of Harvard College | Characterization of individual polymer molecules based on monomer-interface interactions |
| TWI236532B (en) * | 2001-08-28 | 2005-07-21 | Chien Hui Chuan | Multichannel polynucleotide molecule sequencing method |
| CN101619353A (en) * | 2009-08-13 | 2010-01-06 | 上海交通大学 | Method for linking monomolecular DNA to single magnetic bead |
| CN102216783A (en) * | 2008-09-22 | 2011-10-12 | 华盛顿大学 | Msp nanopores and related methods |
| CN107727705A (en) * | 2017-09-28 | 2018-02-23 | 东南大学 | A kind of enzyme reaction detects nano-pore electric sensor |
| CN109459287A (en) * | 2018-12-12 | 2019-03-12 | 浙江大学 | A kind of continuous magnetic separating device and method based on micro-fluidic chip |
| CN110607220A (en) * | 2019-08-01 | 2019-12-24 | 广东工业大学 | Array structure for accurately modifying biomolecules and modification method thereof |
Family Cites Families (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP5764296B2 (en) * | 2010-03-31 | 2015-08-19 | 株式会社日立ハイテクノロジーズ | Characterization of biopolymers |
| GB201313477D0 (en) * | 2013-07-29 | 2013-09-11 | Univ Leuven Kath | Nanopore biosensors for detection of proteins and nucleic acids |
| US10393726B2 (en) * | 2015-03-23 | 2019-08-27 | The University Of North Carolina At Chapel Hill | Universal molecular processor for precision medicine |
| US11639922B2 (en) * | 2017-07-17 | 2023-05-02 | President And Fellows Of Harvard College | Nanopore-matched protein shuttle for molecular characterization and methodology for data analysis thereof |
-
2020
- 2020-01-14 CN CN202010039072.2A patent/CN111235224B/en active Active
Patent Citations (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5795782A (en) * | 1995-03-17 | 1998-08-18 | President & Fellows Of Harvard College | Characterization of individual polymer molecules based on monomer-interface interactions |
| TWI236532B (en) * | 2001-08-28 | 2005-07-21 | Chien Hui Chuan | Multichannel polynucleotide molecule sequencing method |
| CN102216783A (en) * | 2008-09-22 | 2011-10-12 | 华盛顿大学 | Msp nanopores and related methods |
| CN101619353A (en) * | 2009-08-13 | 2010-01-06 | 上海交通大学 | Method for linking monomolecular DNA to single magnetic bead |
| CN107727705A (en) * | 2017-09-28 | 2018-02-23 | 东南大学 | A kind of enzyme reaction detects nano-pore electric sensor |
| CN109459287A (en) * | 2018-12-12 | 2019-03-12 | 浙江大学 | A kind of continuous magnetic separating device and method based on micro-fluidic chip |
| CN110607220A (en) * | 2019-08-01 | 2019-12-24 | 广东工业大学 | Array structure for accurately modifying biomolecules and modification method thereof |
Also Published As
| Publication number | Publication date |
|---|---|
| CN111235224A (en) | 2020-06-05 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| US10513434B2 (en) | Nanopipette apparatus for manipulating cells | |
| US6537433B1 (en) | Methods and apparatus for the location and concentration of polar analytes using an alternating electric field | |
| US6176990B1 (en) | Micro-electrophoresis chip for moving and separating nucleic acids and other charged molecules | |
| JP4034351B2 (en) | Light-controlled electrokinetic assembly of particle-proximal surfaces | |
| US7618807B2 (en) | Apparatus for electrophoretic in situ tissue staining | |
| CN101398436B (en) | Rotating micro-example auto-introducing device | |
| CN109709349B (en) | Chemiluminescent immunoassay system | |
| JPH11502618A (en) | Capillary electrophoresis apparatus and method | |
| US8211693B2 (en) | Device for separating and/or analyzing several molecular targets dissolved in a complex mixture | |
| US20110220498A1 (en) | Method for Building Massively-Parallel Preconcentration Device for Multiplexed, High-Throughput Applications | |
| JP2008070210A (en) | Sample analysis method and analyzer | |
| RU2280507C2 (en) | Process and apparatus for making biopolymer matrices | |
| CN111235224B (en) | Accurate biomolecule modification method and device based on magnetophoresis separation | |
| CN110646493A (en) | Microfluidic chip, protein detection method, device and system | |
| JP3977314B2 (en) | Microchip | |
| KR101770557B1 (en) | Biomolecular preconcentrating device | |
| JP2017187443A (en) | Polymer film for analyzer, substrate for analyzer, method of manufacturing polymer film for analyzer, and method of manufacturing substrate for analyzer | |
| KR101759894B1 (en) | Lab-on-a-chip and a method of fabricating thereof | |
| JP4189123B2 (en) | Bio-related substance detection method, chip device and device | |
| JP4608500B2 (en) | Apparatus for receiving fluid sample and method of use thereof | |
| CN114225983B (en) | Microfluidic chip and device for long DNA molecule length screening and application method thereof | |
| Yamamoto et al. | Nylon Monofilament Mold Three-dimensional Microfluidic Chips for Size-exclusion Microchip Electrophoresis: Application to Specific Online Preconcentration of Proteins | |
| JP2012029676A (en) | Cartridge for concentrating and collecting nucleic acid, method for concentrating and collecting nucleic acid and method for fabricating the cartridge | |
| US7871571B2 (en) | Biomolecule analyzing system | |
| KR100588335B1 (en) | Multiple channel electrophoresis chips using fused silica capillary and fabrication method its |
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 | ||
| GR01 | Patent grant | ||
| GR01 | Patent grant |