US20100025249A1 - Systems and Methods for Controlling the Position of a Charged Polymer Inside a Nanopore - Google Patents
Systems and Methods for Controlling the Position of a Charged Polymer Inside a Nanopore Download PDFInfo
- Publication number
- US20100025249A1 US20100025249A1 US12/540,553 US54055309A US2010025249A1 US 20100025249 A1 US20100025249 A1 US 20100025249A1 US 54055309 A US54055309 A US 54055309A US 2010025249 A1 US2010025249 A1 US 2010025249A1
- Authority
- US
- United States
- Prior art keywords
- electrode
- locking
- charged polymer
- nanopore
- time
- 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.)
- Abandoned
Links
Images
Classifications
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
- G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
- G01N33/483—Physical analysis of biological material
- G01N33/487—Physical analysis of biological material of liquid biological material
- G01N33/48707—Physical analysis of biological material of liquid biological material by electrical means
- G01N33/48721—Investigating individual macromolecules, e.g. by translocation through nanopores
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B82—NANOTECHNOLOGY
- B82Y—SPECIFIC USES OR APPLICATIONS OF NANOSTRUCTURES; MEASUREMENT OR ANALYSIS OF NANOSTRUCTURES; MANUFACTURE OR TREATMENT OF NANOSTRUCTURES
- B82Y15/00—Nanotechnology for interacting, sensing or actuating, e.g. quantum dots as markers in protein assays or molecular motors
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B82—NANOTECHNOLOGY
- B82Y—SPECIFIC USES OR APPLICATIONS OF NANOSTRUCTURES; MEASUREMENT OR ANALYSIS OF NANOSTRUCTURES; MANUFACTURE OR TREATMENT OF NANOSTRUCTURES
- B82Y30/00—Nanotechnology for materials or surface science, e.g. nanocomposites
-
- 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
- C12Q1/6869—Methods for sequencing
-
- 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
- C12Q1/6816—Hybridisation assays characterised by the detection means
- C12Q1/6825—Nucleic acid detection involving sensors
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N15/00—Investigating characteristics of particles; Investigating permeability, pore-volume, or surface-area of porous materials
- G01N2015/0038—Investigating nanoparticles
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y10—TECHNICAL SUBJECTS COVERED BY FORMER USPC
- Y10S—TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y10S977/00—Nanotechnology
- Y10S977/902—Specified use of nanostructure
- Y10S977/904—Specified use of nanostructure for medical, immunological, body treatment, or diagnosis
- Y10S977/924—Specified use of nanostructure for medical, immunological, body treatment, or diagnosis using nanostructure as support of dna analysis
Definitions
- the present invention relates to polymer characterization and, more particularly, to systems and methods for controlling the position of a charged polymer inside a nanopore.
- polymer characterization Rapid, reliable, and inexpensive characterization of polymers, particularly the sequencing of nucleic acids, has become increasingly important.
- One potential application of polymer characterization is in the field of personalized medicine.
- potential benefits of polymer characterization may include treatment of disease by identifying patients who will gain the greatest benefit from a particular medicine, and those who are most at risk of adverse reactions.
- the ability to read individual genomes quickly and economically would be a beneficial tool in the development of personalized medicine.
- nanopore sequencing which includes driving DNA through a nanopore and measuring the electrical current in the DNA as a function of the nucleotides inside the nanopore.
- Some existing approaches attempt to thread a long DNA molecule through a few nanometer-wide nanopore and use physical differences between the four base types to read the sequence of bases in DNA The price of nanopore sequencing is expected to be very low since the method needs neither expensive chemical reagents nor expensive optical readout.
- single nucleotide resolution has not yet been achieved.
- Existing approaches using nanopore sequencing cannot resolve a single base, but, rather, require at least a few dozen bases.
- Some existing approaches rely on using a readily available-in-nature biological nanopore, that is, ⁇ -hemolysin channel (for example, U.S. Pat. No. 5,795,782 entitled “Characterization of individual polymer molecules based on monomer-interface interactions.”).
- Some existing approaches detect events of DNA translocation through a nanopore by measuring sub-millisecond blockades of ionic current through the nanopore but fail to resolve single bases within the translocated molecule.
- the difficulties of dealing with unreliable and poorly understood membrane proteins lead many researches to use solid-state nanopores.
- Nanopores with diameters of between two and three nanometers (nm), fabricated by using such materials as Si 3 N 4 or SiO 2 (for example, U.S. Pat. No. 6,627,067 entitled “Molecular and atomic scale evaluation of biopolymers,” and U.S. Patent Application No. 2006/0063171 entitled “Methods and apparatus for characterizing polynucleotides.”).
- Solid-state nanopores also provide the possibility of placing metal electrodes in the vicinity of probed DNA. This arrangement, in theory, allows researchers to measure the tunnel current through a single base, and, consequentially, potentially discriminate the bases of different types. In existing approaches, however, repetitive measurements of tunnel current are necessary to provide enough statistics to determine the base type with a high degree of accuracy.
- Principles of the present invention provide techniques for controlling the position of a charged polymer inside a nanopore.
- a technique for controlling the position of a linear charged polymer inside a nanopore includes the following steps. Electrostatic control is used to position a linear charged polymer inside a nanopore. Also, an electrostatic potential well is created inside the nanopore, wherein the electrostatic potential well controls a position of the linear charged polymer inside the nanopore.
- a technique for characterizing a linear charged polymer includes the following steps.
- a time-dependent voltage is applied to each of two or more drag electrodes to attract a linear charged polymer from a part of a reservoir preceding a nanopore (that is, a CIS part) to a part of a reservoir following the nanopore (that is, a TRANS part). Entry of the linear charged polymer inside the nanopore is detected.
- the time-dependent voltages are reduced or removed from the two or more drag electrodes.
- a time-dependent voltage is applied to each of one or more locking electrodes to create an electrostatic potential well, wherein the electrostatic potential well controls a position of the linear charged polymer.
- One or more characterization activities are performed on one or more monomers of the linear charged polymer.
- the time-dependent voltage is reduced from each of the locking electrodes and the electrostatic potential well.
- the time-dependent voltages are increased or reapplied to each drag electrode to translocate the linear charge polymer by one or more monomers.
- an apparatus for controlling the position of a linear charged polymer inside a nanopore includes the following components.
- a reservoir is included that is separated by a membrane into two parts (that is, the CIS part and the TRANS part), wherein the membrane is formed as a stack of one or more locking electrodes.
- a nanopore is included in the membrane, wherein the nanopore connects the two parts of the reservoir.
- a drag electrode is in each part of the reservoir.
- the apparatus includes a control unit, wherein the control unit outputs time-dependent voltages to each drag electrode and each locking electrode.
- principles of the invention overcome such shortcomings by, for example, controlling the position of a polymer (for example, DNA) inside a nanopore with single monomer (for example, nucleotide) accuracy.
- a polymer for example, DNA
- single monomer for example, nucleotide
- FIG. 1 is a diagram illustrating a cross-section of an exemplary polymer position control device, according to an embodiment of the present invention
- FIG. 2 is a diagram illustrating exemplary applications of time-dependent voltages, according to an embodiment of the present invention
- FIG. 3 is a diagram illustrating exemplary locking electrode geometries, according to an embodiment of the present invention.
- FIG. 4 is a flow diagram illustrating techniques for controlling the position of a linear charged polymer inside a nanopore, according to an embodiment of the present invention.
- FIG. 5 is a flow diagram illustrating techniques for characterizing a linear charged polymer, according to an embodiment of the present invention.
- Electrostatic control is used to position and move a polymer such as, for example, deoxyribonucleic acid (DNA), inside a nanopore.
- Principles of the present invention apply varying voltages to metal layers in order to produce sensitive control of the position of negatively-charged nucleotides.
- the control may be similar to the charge control in charge-coupled device (CDD) sensors.
- CDD charge-coupled device
- One or more embodiments of the present invention detect nucleotide type by measuring tunnel current of capacitance change between layers. Also, layer voltages may be modulated with high frequency signals in order to utilize lock-in measurement techniques.
- Principles of the present invention are applicable to all linear polymers carrying localized charges along their chain.
- such polymers may include DNA in solution, which is a charged polymer, carrying negative electrical charges on phosphate groups in the double helix of the molecule.
- FIG. 1 is a diagram illustrating a cross-section of an exemplary polymer position control device, according to an embodiment of the present invention.
- FIG. 1 depicts an apparatus for controlling the position of a linear charged polymer inside a nanopore including a reservoir 101 that is divided by a membrane 102 into two parts, the CIS part 103 (preceding the nanopore) and the TRANS part 104 (following the nanopore).
- a membrane 102 is formed as a stack of one or more electrodes 106 , 107 , 108 separated by insulators 115 and 116 .
- the electrical potential of each electrode (V 1 , V 2 , V 3 ) is set independently by control unit 109 .
- Electrodes 106 , 107 , and 108 are referred to as locking electrodes.
- V 1 , V 2 , V 3 are the respective voltages for electrodes 106 , 107 , 108 .
- the voltages connect to the locking electrodes via wires 120 , 121 and 122 , respectively.
- the stack of locking electrodes can include a first locking electrode and a second locking electrode separated by one or more insulators.
- Locking electrodes are capable of creating the electrostatic potential well 114 inside the nanopore by, for example, creating a potential difference between the electrodes.
- electrode 106 may receive a voltage of 0 volts
- electrode 107 may receive a voltage of 1 volts
- electrode 108 may receive a voltage of 0 volts, resulting in the creation of a potential well.
- Control unit 109 provides bias Cis voltage (V c ) to electrode 110 in the CIS part 103 via wire 123 , and also provides Trans voltage (V t ) to electrode 111 in the TRANS part of the reservoir 104 via wire 124 .
- Electrodes 110 and 111 are referred to as drag electrodes. It is to be appreciated, however, that other embodiments of the present invention may include two or more drag electrodes.
- Linear polymer 112 with localized charges 113 may be, for example, originally located in the CIS part 103 .
- the voltage difference V t ⁇ V c (drag voltage) attracts the polymer from CIS 103 to the TRANS part 104 .
- Control unit 109 detects the entrance of polymer inside the nanopore 105 . The detection can be accomplished, for example, by measuring the variation of ion current between drag electrodes 110 and 111 , or locking electrodes 106 , 107 and 108 . In a preferred embodiment, the measurement is made between drag electrode 110 and drag electrode 111 . It is to be appreciated, however, that measurements can also made using any combination of locking and drag electrodes.
- the drag voltage is reduced or removed and voltages are applied to locking electrodes (for example, 106 , 107 and 108 ) to create a potential well 114 .
- the drag electrodes and locking electrodes can be controlled independently, or can be connected in parallel.
- the locking and drag electrodes may be made or created from any conductive material (for example, gold, carbon, etc.).
- the locking electrodes may have one or more geometries, as illustrated by FIG. 3 below.
- the above apparatus can be used to sequence polymers such as, for example, DNA, ribonucleic acid (RNA), protein molecules and other charged polymers, as well as in processes such as, for example, chemical modification of polymers.
- sequence polymers such as, for example, DNA, ribonucleic acid (RNA), protein molecules and other charged polymers, as well as in processes such as, for example, chemical modification of polymers.
- Principles of the present invention may also be used to count the number of polymers with a given characteristic that are present in the solution originally in the CIS reservoir, such as would be needed to measure the number of RNA transcripts in cellular extract.
- One or more embodiments of the present invention may also be used to separate polymers with one or more specific characteristics from the solution on the CIS part to the solution on the TRANS part.
- three locking electrodes are used. It is to be appreciated, however, that one or more locking electrodes may be used in other embodiments.
- a potential well is created as a result of the voltage of the locking electrode. For example, a locking electrode with a voltage of 1 volt may create a potential well in a surrounding environment of lower or neutral voltage.
- locking electrodes 106 , 107 and 108 are shown to have cylindrical geometry (for example, metal plain with a hole). In other embodiments of the present invention, however, the geometry of the locking electrodes and drag electrodes can vary.
- an illustrative embodiment may include two electrodes per layer, each occupying a half plain with a hole in the center.
- a hole is representative of a nanopore
- a layer represents electrodes without a hole
- a half plain represents a geometry that has been divided into two sections.
- a potential well can have one or more spatially dependent profiles.
- FIG. 1 depicts a potential well 114 having a trapezoidal spatially dependent profile.
- one nanopore is used. It is to be appreciated, however, that one or more nanopores can be used in other embodiments wherein, for example, more than one polymer is being positionally controlled and/or more than one portion of a polymer is being positionally controlled.
- a preferred embodiment of the present invention includes a control unit. It is to be appreciated, however, that other embodiments may include one or more control units.
- a control unit may include, for example, a computer that connects to a specialized board with an application-specific integrated circuit (ASIC), wherein the board connects to the device.
- a control unit may also, for example, be integrated with the device by way of a Nano-Electro-Mechanical System (NEMS), wherein a nanofluidics part (for example, a reservoir with DNA) can be combined with electronics (for example, a control unit).
- NEMS Nano-Electro-Mechanical System
- a control unit implements the step of applying time-dependent voltages to the drag electrodes to attract a linear charged polymer from a CIS part of a reservoir to a TRANS part of a reservoir, as well as the step of applying a time-dependent voltage to each locking electrode to create an electrostatic potential well, wherein the electrostatic potential well controls the position of the linear charged polymer.
- control unit implements the steps of detecting entry of the linear charged polymer inside the nanopore, and reducing the time-dependent voltages from the drag electrodes.
- a control unit may also implement the steps of performing one or more characterization activities on a monomer of the linear charged polymer, reducing the time-dependent voltage from each locking electrode and the electrostatic potential well, and increasing or re-applying the time-dependent voltages to the drag electrodes to translocate the linear charge polymer by one or more monomers.
- control unit may implement repetition of one or more actions.
- Such actions may include, for example, reducing or removing the time-dependent voltages from the drag electrodes, and increasing or re-applying the time-dependent voltage to each locking electrode to create an electrostatic potential well.
- Such repeated actions may also include, for example, performing one or more characterization activities on a monomer of the linear charged polymer, reducing or removing the time-dependent voltage from each locking electrode and the electrostatic potential well, and increasing or re-applying the time-dependent voltages to the drag electrodes to translocate the linear charge polymer by one or more monomers.
- control unit implements repetition of the above steps for an entire polymer.
- FIG. 2 is a diagram illustrating exemplary applications of time-dependent voltages, according to an embodiment of the present invention.
- FIG. 2 depicts three positions, a lock position 204 , a move position 205 and a lock position 206 . Moving a potential wave drags the one or more trapped charges, and stopping the wave localizes the one or more charges.
- FIG. 2 also depicts application of time-depiction voltages to three separate electrodes.
- a preferred embodiment of the present invention includes two drag electrodes (V c 110 and V t 111 ) and three locking electrodes ( 106 , 107 and 108 ) with corresponding electrical potential (V 1 , V 2 and V 3 , respectively).
- FIG. 2 exemplary application of time-dependent voltages are depicted for each drag electrode ( 202 and 203 ) as well as for the second or middle locking electrode ( 201 ). As way of example only, application of time-dependent voltages may proceed as follows.
- the voltage application (V 2 ) for the second or middle locking electrode may include 1 volt in lock position 204 , 0 volts in move position 205 , and 1 volt in lock position 206 (the first and third locking electrodes, for example, 106 and 108 , would have voltage levels that remain constant).
- the voltage application (V c ) for drag electrode 110 may include 0 volts in lock position 204 , ⁇ 1 volt in move position 205 , and 0 volts in lock position 206 .
- the voltage application (V t ) for drag electrode 111 may include 0 volts in lock position 204 , 1 volt in move position 205 , and 0 volts in lock position 206 .
- FIG. 3 is a diagram illustrating exemplary locking electrode geometries, according to an embodiment of the present invention.
- FIG. 3 depicts two exemplary locking electrode geometries, namely, a cylindrical geometry 302 and a half plain geometry 306 , both of which include a nanopore 301 .
- the exemplary half plain geometry 306 includes an insulator 305 separating independently-controlled locking electrodes 303 and 304 .
- FIG. 4 is a flow diagram illustrating techniques for controlling the position of a linear charged polymer inside a nanopore, according to an embodiment of the present invention.
- Step 402 includes using electrostatic control to position a linear charged polymer inside a nanopore.
- Step 404 includes creating an electrostatic potential well inside the nanopore, wherein the electrostatic potential well controls a position of the linear charged polymer inside the nanopore.
- the linear charged polymer may include, for example, DNA, RNA and/or one or more protein molecules.
- One or more embodiments of the present invention may also include the step of detecting entry of the linear charged polymer inside the nanopore. Detecting entry of the linear charged polymer may include measuring a variation of ion current between the drag electrodes.
- FIG. 5 is a flow diagram illustrating techniques for characterizing a linear charged polymer, according to an embodiment of the present invention.
- Step 502 includes applying a time-dependent voltage to each of two or more drag electrodes to attract a linear charged polymer from a first part of a reservoir to a second part of a reservoir.
- the first part of the reservoir may include a CIS part and the second part of the reservoir may include a TRANS part.
- Step 504 includes detecting entry of the linear charged polymer inside a nanopore.
- Step 506 includes reducing the time-dependent voltage from each drag electrode.
- Step 508 includes applying a time-dependent voltage to each of one or more locking electrodes to create an electrostatic potential well, wherein the electrostatic potential well controls a position of the linear charged polymer.
- Step 510 includes performing one or more characterization activities on a monomer of the linear charged polymer.
- An illustrative embodiment of the invention may also include the step of reducing the time-dependent voltage from each locking electrode and the electrostatic potential well, as well as the step of increasing the time-dependent voltage to each drag electrode to translocate the linear charged polymer by one or more monomers.
- One or more embodiments of the present invention may also include repetition of one or more steps. Steps to be considered for repetition may include, for example, reducing or removing the time-dependent voltage from each drag electrode, and applying a time-dependent voltage to each locking electrode to create an electrostatic potential well. Steps to be considered for repetition may also include, for example, performing one or more characterization activities on a monomer of the linear charged polymer, reducing or removing the time-dependent voltage from each locking electrode and the electrostatic potential well, and increasing the time-dependent voltage to each drag electrode to translocate the linear charge polymer by one or more monomers. Also, in an illustrative embodiment of the present invention, the above-mentioned steps are repeated for an entire polymer.
- Characterization activities may include, for example, DNA sequencing, counting the number of polymers with a given characteristic that are present in a solution originally in the CIS part of a reservoir, counting the number of monomers in each polymer, as well as separating two or more polymers according to one or more characteristics.
- Other characterization activities may include chemical modification of the linear charged polymer may occur, as well as measuring tunnel current between a first locking electrode and a second locking electrode, and measuring capacitance change between a first locking electrode and a second locking electrode.
- the step of increasing the time-dependent voltage to each drag electrode may include re-applying each time-dependent voltage. Also, increasing the time-dependent voltage to each drag electrodes may be performed for the duration of a selected time interval, wherein the time interval is sufficient to translocate each polymer by one monomer. A linear charged polymer may be translocated in both directions.
- the step of reducing the time-dependent voltage from each drag electrode may include removing each time-dependent voltage completely.
- an exemplary technique for characterizing a linear charged polymers may occur as follows.
- a linear polymer with localized charges may be, for example, originally located in the CIS part of the reservoir.
- the voltage difference of V t ⁇ V c drag voltage attracts the polymer from CIS part to the TRANS part of the reservoir.
- a control unit detects the entrance of the polymer inside the nanopore, wherein the detection can be accomplished, for example, by measuring the variation of ion current between drag electrodes or locking electrodes.
- the drag voltage is reduced or removed and a voltage is applied to each locking electrode to create an electrostatic potential well.
- the depth of a potential well can be, for example, sufficient to lock at least one point charge or monomer. After the polymer is locked, measurements of the monomer contained in the potential well are initiated.
- T is selected on a basis that would translocate the polymer by a certain required distance such as, for example, the distance between localized charges. In a preferred embodiment of the present invention, this distance corresponds to the length of a single monomer.
- Translocation of a polymer may be executed in both directions in order to double-check the measured DNA sequence.
- the above-described steps are repeated until the polymer completely translocates from the CIS part of the reservoir to the TRANS part of the reservoir and leaves the nanopore.
- the sequence of drag and locking voltage application illustrated in FIG. 5 is an exemplary embodiment of the invention. It is to be appreciated that the sequence of drag and locking voltage application can vary.
Abstract
Description
- This application is a divisional application under 37 CFR §1.53(b) of U.S. application Ser. No. 11/670,621 filed Feb. 2, 2007, incorporated by reference herein.
- The present invention relates to polymer characterization and, more particularly, to systems and methods for controlling the position of a charged polymer inside a nanopore.
- Rapid, reliable, and inexpensive characterization of polymers, particularly the sequencing of nucleic acids, has become increasingly important. One potential application of polymer characterization is in the field of personalized medicine. For example, potential benefits of polymer characterization may include treatment of disease by identifying patients who will gain the greatest benefit from a particular medicine, and those who are most at risk of adverse reactions. The ability to read individual genomes quickly and economically would be a beneficial tool in the development of personalized medicine.
- Existing approaches have attempted to address the need for rapid, reliable and inexpensive polymer characterization. For example, some existing approaches use sequencing by synthesis, which includes detection of optical signals during synthesis of complementary deoxyribonucleic acid (DNA) strands. However, sequencing by synthesis produces problems such as, for example, slow reagent cycling times (tens of seconds), short read lengths (tens to hundreds of bases) and expensive reagents. Slow reagent cycling times is a fundamental problem because it results in a need to change chemistry in a flow cell to remove fluorophore from each incorporated base.
- Also, other exiting approaches use nanopore sequencing, which includes driving DNA through a nanopore and measuring the electrical current in the DNA as a function of the nucleotides inside the nanopore. Some existing approaches attempt to thread a long DNA molecule through a few nanometer-wide nanopore and use physical differences between the four base types to read the sequence of bases in DNA The price of nanopore sequencing is expected to be very low since the method needs neither expensive chemical reagents nor expensive optical readout. However, single nucleotide resolution has not yet been achieved. Existing approaches using nanopore sequencing cannot resolve a single base, but, rather, require at least a few dozen bases.
- Some existing approaches rely on using a readily available-in-nature biological nanopore, that is, α-hemolysin channel (for example, U.S. Pat. No. 5,795,782 entitled “Characterization of individual polymer molecules based on monomer-interface interactions.”). Some existing approaches detect events of DNA translocation through a nanopore by measuring sub-millisecond blockades of ionic current through the nanopore but fail to resolve single bases within the translocated molecule. Despite the ease of obtaining biological nanopores, the difficulties of dealing with unreliable and poorly understood membrane proteins lead many researches to use solid-state nanopores.
- Other existing approaches use nanopores with diameters of between two and three nanometers (nm), fabricated by using such materials as Si3N4 or SiO2 (for example, U.S. Pat. No. 6,627,067 entitled “Molecular and atomic scale evaluation of biopolymers,” and U.S. Patent Application No. 2006/0063171 entitled “Methods and apparatus for characterizing polynucleotides.”). Solid-state nanopores also provide the possibility of placing metal electrodes in the vicinity of probed DNA. This arrangement, in theory, allows researchers to measure the tunnel current through a single base, and, consequentially, potentially discriminate the bases of different types. In existing approaches, however, repetitive measurements of tunnel current are necessary to provide enough statistics to determine the base type with a high degree of accuracy.
- Existing approaches in the area of mechanical polymer characterization include U.S. Patent Application No. 2006/0057585 entitled “Nanostepper/Sensor Systems and Methods of Use Thereof,” filed Sep. 10, 2004. This approach includes a nanopore system and a first nanostepper system, wherein the nanopore system includes a structure having a nanopore aperture, and the first nanostepper system includes an x-/y-direction moving structure and a first nanostepper arm positioned adjacent the structure.
- At present, nanopore sequencing is still theoretical, as single nucleotide resolution has not yet been achieved. One of the possible reasons for such unsuccessful experimental results in existing approaches is that the translocation of DNA through the nanopore is too fast and erratic for current measurement methods to reliably resolve the type of a single nucleotide. Despite attempts to slow down the translocation speed by optimization of various parameters (for example, electrolyte temperature, salt concentration, viscosity, and the electrical bias voltage across the nanopore), existing approaches have still been unsuccessful in attaining single nucleotide resolution.
- It would thus be desirable to overcome these and other limitations in existing polymer characterization approaches.
- Principles of the present invention provide techniques for controlling the position of a charged polymer inside a nanopore.
- For example, in one aspect of the invention, a technique for controlling the position of a linear charged polymer inside a nanopore includes the following steps. Electrostatic control is used to position a linear charged polymer inside a nanopore. Also, an electrostatic potential well is created inside the nanopore, wherein the electrostatic potential well controls a position of the linear charged polymer inside the nanopore.
- In another aspect of the invention, a technique for characterizing a linear charged polymer includes the following steps. A time-dependent voltage is applied to each of two or more drag electrodes to attract a linear charged polymer from a part of a reservoir preceding a nanopore (that is, a CIS part) to a part of a reservoir following the nanopore (that is, a TRANS part). Entry of the linear charged polymer inside the nanopore is detected. The time-dependent voltages are reduced or removed from the two or more drag electrodes. A time-dependent voltage is applied to each of one or more locking electrodes to create an electrostatic potential well, wherein the electrostatic potential well controls a position of the linear charged polymer. One or more characterization activities are performed on one or more monomers of the linear charged polymer. The time-dependent voltage is reduced from each of the locking electrodes and the electrostatic potential well. Also, the time-dependent voltages are increased or reapplied to each drag electrode to translocate the linear charge polymer by one or more monomers.
- In another aspect of the invention, an apparatus for controlling the position of a linear charged polymer inside a nanopore includes the following components. A reservoir is included that is separated by a membrane into two parts (that is, the CIS part and the TRANS part), wherein the membrane is formed as a stack of one or more locking electrodes. A nanopore is included in the membrane, wherein the nanopore connects the two parts of the reservoir. A drag electrode is in each part of the reservoir. Also, the apparatus includes a control unit, wherein the control unit outputs time-dependent voltages to each drag electrode and each locking electrode.
- In contrast to the above-mentioned limitations in existing approaches, principles of the invention overcome such shortcomings by, for example, controlling the position of a polymer (for example, DNA) inside a nanopore with single monomer (for example, nucleotide) accuracy.
- These and other objects, features and advantages of the present invention will become apparent from the following detailed description of illustrative embodiments thereof, which is to be read in connection with the accompanying drawings.
-
FIG. 1 is a diagram illustrating a cross-section of an exemplary polymer position control device, according to an embodiment of the present invention; -
FIG. 2 is a diagram illustrating exemplary applications of time-dependent voltages, according to an embodiment of the present invention; -
FIG. 3 is a diagram illustrating exemplary locking electrode geometries, according to an embodiment of the present invention; -
FIG. 4 is a flow diagram illustrating techniques for controlling the position of a linear charged polymer inside a nanopore, according to an embodiment of the present invention; and -
FIG. 5 is a flow diagram illustrating techniques for characterizing a linear charged polymer, according to an embodiment of the present invention. - As noted above, it would be beneficial to not only slow down the translocation of charged polymers, but to control the position of a polymer inside a nanopore with single nucleotide accuracy. Principles of the present invention use an electrostatic potential well to lock the positions of linear polymers carrying localized charges along their chain. Electrostatic control (ESC) is used to position and move a polymer such as, for example, deoxyribonucleic acid (DNA), inside a nanopore.
- Principles of the present invention apply varying voltages to metal layers in order to produce sensitive control of the position of negatively-charged nucleotides. The control may be similar to the charge control in charge-coupled device (CDD) sensors.
- One or more embodiments of the present invention detect nucleotide type by measuring tunnel current of capacitance change between layers. Also, layer voltages may be modulated with high frequency signals in order to utilize lock-in measurement techniques.
- Principles of the present invention are applicable to all linear polymers carrying localized charges along their chain. For example, such polymers may include DNA in solution, which is a charged polymer, carrying negative electrical charges on phosphate groups in the double helix of the molecule.
- Given the above realizations made in accordance with one or more embodiments of the present invention, and general features associated therewith, the remainder of the detailed description will provide an illustrative explanation of techniques for implementing such realizations and features in the context of
FIGS. 1 through 5 . -
FIG. 1 is a diagram illustrating a cross-section of an exemplary polymer position control device, according to an embodiment of the present invention. By way of illustration,FIG. 1 depicts an apparatus for controlling the position of a linear charged polymer inside a nanopore including areservoir 101 that is divided by amembrane 102 into two parts, the CIS part 103 (preceding the nanopore) and the TRANS part 104 (following the nanopore). Amembrane 102 is formed as a stack of one ormore electrodes insulators control unit 109.Electrodes electrodes wires -
CIS 103 andTRANS 104 parts are connected by ananopore 105 in themembrane 102. Locking electrodes (for example, 106, 107, 108) are capable of creating the electrostaticpotential well 114 inside the nanopore by, for example, creating a potential difference between the electrodes. As way of example,electrode 106 may receive a voltage of 0 volts,electrode 107 may receive a voltage of 1 volts, andelectrode 108 may receive a voltage of 0 volts, resulting in the creation of a potential well. -
Control unit 109 provides bias Cis voltage (Vc) toelectrode 110 in theCIS part 103 viawire 123, and also provides Trans voltage (Vt) toelectrode 111 in the TRANS part of thereservoir 104 viawire 124.Electrodes -
Linear polymer 112 withlocalized charges 113 may be, for example, originally located in theCIS part 103. The voltage difference Vt−Vc (drag voltage) attracts the polymer fromCIS 103 to theTRANS part 104.Control unit 109 detects the entrance of polymer inside thenanopore 105. The detection can be accomplished, for example, by measuring the variation of ion current betweendrag electrodes electrodes drag electrode 110 anddrag electrode 111. It is to be appreciated, however, that measurements can also made using any combination of locking and drag electrodes. - Once the polymer is inside the
nanopore 105, the drag voltage is reduced or removed and voltages are applied to locking electrodes (for example, 106, 107 and 108) to create apotential well 114. - The drag electrodes and locking electrodes can be controlled independently, or can be connected in parallel. In addition, the locking and drag electrodes may be made or created from any conductive material (for example, gold, carbon, etc.). Also, the locking electrodes may have one or more geometries, as illustrated by
FIG. 3 below. - In one or more embodiments of the present invention, the above apparatus can be used to sequence polymers such as, for example, DNA, ribonucleic acid (RNA), protein molecules and other charged polymers, as well as in processes such as, for example, chemical modification of polymers.
- Principles of the present invention may also be used to count the number of polymers with a given characteristic that are present in the solution originally in the CIS reservoir, such as would be needed to measure the number of RNA transcripts in cellular extract. One or more embodiments of the present invention may also be used to separate polymers with one or more specific characteristics from the solution on the CIS part to the solution on the TRANS part.
- In a preferred embodiment, three locking electrodes are used. It is to be appreciated, however, that one or more locking electrodes may be used in other embodiments. In an embodiment wherein one locking electrode is used, a potential well is created as a result of the voltage of the locking electrode. For example, a locking electrode with a voltage of 1 volt may create a potential well in a surrounding environment of lower or neutral voltage. In
FIG. 1 , lockingelectrodes FIG. 3 below, a hole is representative of a nanopore, a layer represents electrodes without a hole, and a half plain represents a geometry that has been divided into two sections. - A potential well can have one or more spatially dependent profiles. As way of example,
FIG. 1 depicts apotential well 114 having a trapezoidal spatially dependent profile. In a preferred embodiment, one nanopore is used. It is to be appreciated, however, that one or more nanopores can be used in other embodiments wherein, for example, more than one polymer is being positionally controlled and/or more than one portion of a polymer is being positionally controlled. - A preferred embodiment of the present invention includes a control unit. It is to be appreciated, however, that other embodiments may include one or more control units. A control unit may include, for example, a computer that connects to a specialized board with an application-specific integrated circuit (ASIC), wherein the board connects to the device. A control unit may also, for example, be integrated with the device by way of a Nano-Electro-Mechanical System (NEMS), wherein a nanofluidics part (for example, a reservoir with DNA) can be combined with electronics (for example, a control unit). A control unit implements the step of applying time-dependent voltages to the drag electrodes to attract a linear charged polymer from a CIS part of a reservoir to a TRANS part of a reservoir, as well as the step of applying a time-dependent voltage to each locking electrode to create an electrostatic potential well, wherein the electrostatic potential well controls the position of the linear charged polymer.
- Moreover, in an illustrative embodiment of the present invention, the control unit implements the steps of detecting entry of the linear charged polymer inside the nanopore, and reducing the time-dependent voltages from the drag electrodes.
- A control unit may also implement the steps of performing one or more characterization activities on a monomer of the linear charged polymer, reducing the time-dependent voltage from each locking electrode and the electrostatic potential well, and increasing or re-applying the time-dependent voltages to the drag electrodes to translocate the linear charge polymer by one or more monomers.
- Also, in one or more embodiments of the present invention, the control unit may implement repetition of one or more actions. Such actions may include, for example, reducing or removing the time-dependent voltages from the drag electrodes, and increasing or re-applying the time-dependent voltage to each locking electrode to create an electrostatic potential well. Such repeated actions may also include, for example, performing one or more characterization activities on a monomer of the linear charged polymer, reducing or removing the time-dependent voltage from each locking electrode and the electrostatic potential well, and increasing or re-applying the time-dependent voltages to the drag electrodes to translocate the linear charge polymer by one or more monomers.
- In an illustrative embodiment of the invention, the control unit implements repetition of the above steps for an entire polymer.
-
FIG. 2 is a diagram illustrating exemplary applications of time-dependent voltages, according to an embodiment of the present invention. By way of illustration,FIG. 2 depicts three positions, alock position 204, amove position 205 and alock position 206. Moving a potential wave drags the one or more trapped charges, and stopping the wave localizes the one or more charges.FIG. 2 also depicts application of time-depiction voltages to three separate electrodes. - As illustrated in
FIG. 1 , a preferred embodiment of the present invention includes two drag electrodes (V c 110 and Vt 111) and three locking electrodes (106, 107 and 108) with corresponding electrical potential (V1, V2 and V3, respectively). InFIG. 2 , exemplary application of time-dependent voltages are depicted for each drag electrode (202 and 203) as well as for the second or middle locking electrode (201). As way of example only, application of time-dependent voltages may proceed as follows. In 201, the voltage application (V2) for the second or middle locking electrode (for example, 107) may include 1 volt inlock position 204, 0 volts inmove position 205, and 1 volt in lock position 206 (the first and third locking electrodes, for example, 106 and 108, would have voltage levels that remain constant). In 202, the voltage application (Vc) fordrag electrode 110 may include 0 volts inlock position 204, −1 volt inmove position 205, and 0 volts inlock position 206. In 203, the voltage application (Vt) fordrag electrode 111 may include 0 volts inlock position 204, 1 volt inmove position 205, and 0 volts inlock position 206. -
FIG. 3 is a diagram illustrating exemplary locking electrode geometries, according to an embodiment of the present invention. By way of illustration,FIG. 3 depicts two exemplary locking electrode geometries, namely, acylindrical geometry 302 and a halfplain geometry 306, both of which include ananopore 301. Also, the exemplary halfplain geometry 306 includes aninsulator 305 separating independently-controlledlocking electrodes -
FIG. 4 is a flow diagram illustrating techniques for controlling the position of a linear charged polymer inside a nanopore, according to an embodiment of the present invention. Step 402 includes using electrostatic control to position a linear charged polymer inside a nanopore. Step 404 includes creating an electrostatic potential well inside the nanopore, wherein the electrostatic potential well controls a position of the linear charged polymer inside the nanopore. The linear charged polymer may include, for example, DNA, RNA and/or one or more protein molecules. - One or more embodiments of the present invention may also include the step of detecting entry of the linear charged polymer inside the nanopore. Detecting entry of the linear charged polymer may include measuring a variation of ion current between the drag electrodes.
-
FIG. 5 is a flow diagram illustrating techniques for characterizing a linear charged polymer, according to an embodiment of the present invention. Step 502 includes applying a time-dependent voltage to each of two or more drag electrodes to attract a linear charged polymer from a first part of a reservoir to a second part of a reservoir. The first part of the reservoir may include a CIS part and the second part of the reservoir may include a TRANS part. Step 504 includes detecting entry of the linear charged polymer inside a nanopore. Step 506 includes reducing the time-dependent voltage from each drag electrode. Step 508 includes applying a time-dependent voltage to each of one or more locking electrodes to create an electrostatic potential well, wherein the electrostatic potential well controls a position of the linear charged polymer. Step 510 includes performing one or more characterization activities on a monomer of the linear charged polymer. An illustrative embodiment of the invention may also include the step of reducing the time-dependent voltage from each locking electrode and the electrostatic potential well, as well as the step of increasing the time-dependent voltage to each drag electrode to translocate the linear charged polymer by one or more monomers. - One or more embodiments of the present invention may also include repetition of one or more steps. Steps to be considered for repetition may include, for example, reducing or removing the time-dependent voltage from each drag electrode, and applying a time-dependent voltage to each locking electrode to create an electrostatic potential well. Steps to be considered for repetition may also include, for example, performing one or more characterization activities on a monomer of the linear charged polymer, reducing or removing the time-dependent voltage from each locking electrode and the electrostatic potential well, and increasing the time-dependent voltage to each drag electrode to translocate the linear charge polymer by one or more monomers. Also, in an illustrative embodiment of the present invention, the above-mentioned steps are repeated for an entire polymer.
- Characterization activities may include, for example, DNA sequencing, counting the number of polymers with a given characteristic that are present in a solution originally in the CIS part of a reservoir, counting the number of monomers in each polymer, as well as separating two or more polymers according to one or more characteristics. Other characterization activities may include chemical modification of the linear charged polymer may occur, as well as measuring tunnel current between a first locking electrode and a second locking electrode, and measuring capacitance change between a first locking electrode and a second locking electrode.
- The step of increasing the time-dependent voltage to each drag electrode may include re-applying each time-dependent voltage. Also, increasing the time-dependent voltage to each drag electrodes may be performed for the duration of a selected time interval, wherein the time interval is sufficient to translocate each polymer by one monomer. A linear charged polymer may be translocated in both directions.
- The step of reducing the time-dependent voltage from each drag electrode may include removing each time-dependent voltage completely.
- In a preferred embodiment of the invention, an exemplary technique for characterizing a linear charged polymers may occur as follows. A linear polymer with localized charges may be, for example, originally located in the CIS part of the reservoir. The voltage difference of Vt−Vc (drag voltage) attracts the polymer from CIS part to the TRANS part of the reservoir. A control unit detects the entrance of the polymer inside the nanopore, wherein the detection can be accomplished, for example, by measuring the variation of ion current between drag electrodes or locking electrodes.
- Once the polymer is inside the nanopore, the drag voltage is reduced or removed and a voltage is applied to each locking electrode to create an electrostatic potential well. The depth of a potential well can be, for example, sufficient to lock at least one point charge or monomer. After the polymer is locked, measurements of the monomer contained in the potential well are initiated.
- Also, the potential well can be removed, and the drag voltage can be increased or re-applied for a time interval T. The value of T is selected on a basis that would translocate the polymer by a certain required distance such as, for example, the distance between localized charges. In a preferred embodiment of the present invention, this distance corresponds to the length of a single monomer.
- By changing the polarity of drag voltage, it is possible to translocate the polymer in both directions. Translocation of a polymer may be executed in both directions in order to double-check the measured DNA sequence.
- In an illustrative embodiment of the invention, the above-described steps are repeated until the polymer completely translocates from the CIS part of the reservoir to the TRANS part of the reservoir and leaves the nanopore. The sequence of drag and locking voltage application illustrated in
FIG. 5 is an exemplary embodiment of the invention. It is to be appreciated that the sequence of drag and locking voltage application can vary. - Although illustrative embodiments of the present invention have been described herein with reference to the accompanying drawings, it is to be understood that the invention is not limited to those precise embodiments, and that various other changes and modifications may be made by one skilled in the art without departing from the scope or spirit of the invention.
Claims (13)
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US12/540,553 US20100025249A1 (en) | 2007-02-02 | 2009-08-13 | Systems and Methods for Controlling the Position of a Charged Polymer Inside a Nanopore |
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US11/670,621 US8003319B2 (en) | 2007-02-02 | 2007-02-02 | Systems and methods for controlling position of charged polymer inside nanopore |
US12/540,553 US20100025249A1 (en) | 2007-02-02 | 2009-08-13 | Systems and Methods for Controlling the Position of a Charged Polymer Inside a Nanopore |
Related Parent Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
US11/670,621 Division US8003319B2 (en) | 2007-02-02 | 2007-02-02 | Systems and methods for controlling position of charged polymer inside nanopore |
Publications (1)
Publication Number | Publication Date |
---|---|
US20100025249A1 true US20100025249A1 (en) | 2010-02-04 |
Family
ID=39327362
Family Applications (2)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
US11/670,621 Active 2028-01-16 US8003319B2 (en) | 2007-02-02 | 2007-02-02 | Systems and methods for controlling position of charged polymer inside nanopore |
US12/540,553 Abandoned US20100025249A1 (en) | 2007-02-02 | 2009-08-13 | Systems and Methods for Controlling the Position of a Charged Polymer Inside a Nanopore |
Family Applications Before (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
US11/670,621 Active 2028-01-16 US8003319B2 (en) | 2007-02-02 | 2007-02-02 | Systems and methods for controlling position of charged polymer inside nanopore |
Country Status (4)
Country | Link |
---|---|
US (2) | US8003319B2 (en) |
EP (1) | EP2109685B1 (en) |
CA (1) | CA2708782A1 (en) |
WO (1) | WO2008092760A1 (en) |
Cited By (49)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US20090298072A1 (en) * | 2006-06-07 | 2009-12-03 | The Trustees Of Columbia University In The City Of | DNA Sequencing by Nanopore Using Modified Nucleotides |
US20110193570A1 (en) * | 2010-02-08 | 2011-08-11 | Genia Technologies, Inc. | Systems and methods for characterizing a molecule |
US20110201204A1 (en) * | 2010-02-12 | 2011-08-18 | International Business Machines Corporation | Precisely Tuning Feature Sizes on Hard Masks Via Plasma Treatment |
US20110224098A1 (en) * | 2010-03-15 | 2011-09-15 | International Business Machines Corporation | Nanopore Based Device for Cutting Long DNA Molecules into Fragments |
US20110223652A1 (en) * | 2010-03-15 | 2011-09-15 | International Business Machines Corporation | Piezoelectric-based nanopore device for the active control of the motion of polymers through the same |
WO2012173723A1 (en) * | 2011-06-17 | 2012-12-20 | International Business Machines Corp. | Molecular dispensers |
US8354336B2 (en) | 2010-06-22 | 2013-01-15 | International Business Machines Corporation | Forming an electrode having reduced corrosion and water decomposition on surface using an organic protective layer |
WO2013035064A1 (en) * | 2011-09-09 | 2013-03-14 | International Business Machines Corporation | Embedding nanotube inside nanopore for dna translocation |
US8598018B2 (en) | 2010-06-22 | 2013-12-03 | International Business Machines Corporation | Forming an electrode having reduced corrosion and water decomposition on surface using a custom oxide layer |
US8764968B2 (en) | 2011-01-28 | 2014-07-01 | International Business Machines Corporation | DNA sequencing using multiple metal layer structure with organic coatings forming transient bonding to DNA bases |
US8771491B2 (en) | 2009-09-30 | 2014-07-08 | Quantapore, Inc. | Ultrafast sequencing of biological polymers using a labeled nanopore |
US8845880B2 (en) | 2010-12-22 | 2014-09-30 | Genia Technologies, Inc. | Nanopore-based single DNA molecule characterization, identification and isolation using speed bumps |
US8852407B2 (en) | 2011-01-28 | 2014-10-07 | International Business Machines Corporation | Electron beam sculpting of tunneling junction for nanopore DNA sequencing |
US8926904B2 (en) | 2009-05-12 | 2015-01-06 | Daniel Wai-Cheong So | Method and apparatus for the analysis and identification of molecules |
US8962242B2 (en) | 2011-01-24 | 2015-02-24 | Genia Technologies, Inc. | System for detecting electrical properties of a molecular complex |
US8986629B2 (en) | 2012-02-27 | 2015-03-24 | Genia Technologies, Inc. | Sensor circuit for controlling, detecting, and measuring a molecular complex |
US8986524B2 (en) | 2011-01-28 | 2015-03-24 | International Business Machines Corporation | DNA sequence using multiple metal layer structure with different organic coatings forming different transient bondings to DNA |
US9046511B2 (en) | 2013-04-18 | 2015-06-02 | International Business Machines Corporation | Fabrication of tunneling junction for nanopore DNA sequencing |
US9097698B2 (en) | 2013-06-19 | 2015-08-04 | International Business Machines Corporation | Nanogap device with capped nanowire structures |
US9110478B2 (en) | 2011-01-27 | 2015-08-18 | Genia Technologies, Inc. | Temperature regulation of measurement arrays |
US9128078B2 (en) | 2013-06-19 | 2015-09-08 | International Business Machines Corporation | Manufacturable sub-3 nanometer palladium gap devices for fixed electrode tunneling recognition |
US9194838B2 (en) | 2010-03-03 | 2015-11-24 | Osaka University | Method and device for identifying nucleotide, and method and device for determining nucleotide sequence of polynucleotide |
US20160025702A1 (en) * | 2013-03-13 | 2016-01-28 | Arizona Board Of Regents On Behalf Of Arizona State University | Systems, devices and methods for translocation control |
US9322062B2 (en) | 2013-10-23 | 2016-04-26 | Genia Technologies, Inc. | Process for biosensor well formation |
US20160194698A1 (en) * | 2014-12-16 | 2016-07-07 | Arizona Board Of Regents On Behalf Of Arizona State University | Systems, apparatuses and methods for reading polymer sequence |
US9494554B2 (en) | 2012-06-15 | 2016-11-15 | Genia Technologies, Inc. | Chip set-up and high-accuracy nucleic acid sequencing |
US9506894B2 (en) | 2012-12-27 | 2016-11-29 | Quantum Biosystems Inc. | Method for controlling substance moving speed and apparatus for controlling the same |
US9535033B2 (en) | 2012-08-17 | 2017-01-03 | Quantum Biosystems Inc. | Sample analysis method |
US9551697B2 (en) | 2013-10-17 | 2017-01-24 | Genia Technologies, Inc. | Non-faradaic, capacitively coupled measurement in a nanopore cell array |
US9605307B2 (en) | 2010-02-08 | 2017-03-28 | Genia Technologies, Inc. | Systems and methods for forming a nanopore in a lipid bilayer |
US9605309B2 (en) | 2012-11-09 | 2017-03-28 | Genia Technologies, Inc. | Nucleic acid sequencing using tags |
US9624537B2 (en) | 2014-10-24 | 2017-04-18 | Quantapore, Inc. | Efficient optical analysis of polymers using arrays of nanostructures |
US9644236B2 (en) | 2013-09-18 | 2017-05-09 | Quantum Biosystems Inc. | Biomolecule sequencing devices, systems and methods |
US9651539B2 (en) | 2012-10-28 | 2017-05-16 | Quantapore, Inc. | Reducing background fluorescence in MEMS materials by low energy ion beam treatment |
US9678055B2 (en) | 2010-02-08 | 2017-06-13 | Genia Technologies, Inc. | Methods for forming a nanopore in a lipid bilayer |
US9759711B2 (en) | 2013-02-05 | 2017-09-12 | Genia Technologies, Inc. | Nanopore arrays |
US9862997B2 (en) | 2013-05-24 | 2018-01-09 | Quantapore, Inc. | Nanopore-based nucleic acid analysis with mixed FRET detection |
US9885079B2 (en) | 2014-10-10 | 2018-02-06 | Quantapore, Inc. | Nanopore-based polymer analysis with mutually-quenching fluorescent labels |
US9903820B2 (en) | 2007-05-08 | 2018-02-27 | The Trustees Of Boston University | Chemical functionalization of solid-state nanopores and nanopore arrays and applications thereof |
US10029915B2 (en) | 2012-04-04 | 2018-07-24 | International Business Machines Corporation | Functionally switchable self-assembled coating compound for controlling translocation of molecule through nanopores |
US10246479B2 (en) | 2012-04-09 | 2019-04-02 | The Trustees Of Columbia University In The City Of New York | Method of preparation of nanopore and uses thereof |
US10261066B2 (en) | 2013-10-16 | 2019-04-16 | Quantum Biosystems Inc. | Nano-gap electrode pair and method of manufacturing same |
US10421995B2 (en) | 2013-10-23 | 2019-09-24 | Genia Technologies, Inc. | High speed molecular sensing with nanopores |
US10438811B1 (en) | 2014-04-15 | 2019-10-08 | Quantum Biosystems Inc. | Methods for forming nano-gap electrodes for use in nanosensors |
US10443096B2 (en) | 2010-12-17 | 2019-10-15 | The Trustees Of Columbia University In The City Of New York | DNA sequencing by synthesis using modified nucleotides and nanopore detection |
US10732183B2 (en) | 2013-03-15 | 2020-08-04 | The Trustees Of Columbia University In The City Of New York | Method for detecting multiple predetermined compounds in a sample |
US10823721B2 (en) | 2016-07-05 | 2020-11-03 | Quantapore, Inc. | Optically based nanopore sequencing |
US11396677B2 (en) | 2014-03-24 | 2022-07-26 | The Trustees Of Columbia University In The City Of New York | Chemical methods for producing tagged nucleotides |
US11565258B2 (en) | 2016-10-03 | 2023-01-31 | Genvida Technology Company Limited | Method and apparatus for the analysis and identification of molecules |
Families Citing this family (104)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US20100216153A1 (en) | 2004-02-27 | 2010-08-26 | Helicos Biosciences Corporation | Methods for detecting fetal nucleic acids and diagnosing fetal abnormalities |
US7932034B2 (en) | 2006-12-20 | 2011-04-26 | The Board Of Trustees Of The Leland Stanford Junior University | Heat and pH measurement for sequencing of DNA |
US8003319B2 (en) | 2007-02-02 | 2011-08-23 | International Business Machines Corporation | Systems and methods for controlling position of charged polymer inside nanopore |
WO2008124706A2 (en) | 2007-04-06 | 2008-10-16 | Arizona Board Of Regents Acting For And On Behalf Of Arizona State University | Devices and methods for target molecule characterization |
EP2201136B1 (en) | 2007-10-01 | 2017-12-06 | Nabsys 2.0 LLC | Nanopore sequencing by hybridization of probes to form ternary complexes and variable range alignment |
US8628649B2 (en) * | 2008-03-18 | 2014-01-14 | Arizona Board Of Regents Acting For And On Behalf Of Arizona State University | Nanopore and carbon nanotube based DNA sequencer and a serial recognition sequencer |
US8961757B2 (en) * | 2008-03-18 | 2015-02-24 | Arizona Board Of Regents, A Body Corporate Of The State Of Arizona Acting For And On Behalf Of Arizona State University | Nanopore and carbon nanotube based DNA sequencer |
US9650668B2 (en) | 2008-09-03 | 2017-05-16 | Nabsys 2.0 Llc | Use of longitudinally displaced nanoscale electrodes for voltage sensing of biomolecules and other analytes in fluidic channels |
CN102186989B (en) | 2008-09-03 | 2021-06-29 | 纳伯塞斯2.0有限责任公司 | Use of longitudinally displaced nanoscale electrodes for voltage sensing of biomolecules and other analytes in fluidic channels |
US8262879B2 (en) | 2008-09-03 | 2012-09-11 | Nabsys, Inc. | Devices and methods for determining the length of biopolymers and distances between probes bound thereto |
US8968540B2 (en) | 2008-10-06 | 2015-03-03 | Arizona Board Of Regents, A Body Corporate Of The State Of Arizona Acting For And On Behalf Of Arizona State University | Trans-base tunnel reader for sequencing |
WO2010111605A2 (en) * | 2009-03-27 | 2010-09-30 | Nabsys, Inc. | Devices and methods for analyzing biomolecules and probes bound thereto |
US8455260B2 (en) | 2009-03-27 | 2013-06-04 | Massachusetts Institute Of Technology | Tagged-fragment map assembly |
US8246799B2 (en) | 2009-05-28 | 2012-08-21 | Nabsys, Inc. | Devices and methods for analyzing biomolecules and probes bound thereto |
US8864969B2 (en) | 2009-06-25 | 2014-10-21 | The Board Of Trustees Of The Leland Stanford Junior University | Electro-diffusion enhanced bio-molecule charge detection using electrostatic interaction |
WO2011082419A2 (en) * | 2010-01-04 | 2011-07-07 | Life Technologies Corporation | Dna sequencing methods and detectors and systems for carrying out the same |
KR20110100963A (en) * | 2010-03-05 | 2011-09-15 | 삼성전자주식회사 | Microfluidic device and method for deterimining sequences of target nucleic acids using the same |
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 |
US8557529B2 (en) * | 2010-04-09 | 2013-10-15 | International Business Machines Corporation | Nanopore capture system |
US8940148B2 (en) | 2010-06-22 | 2015-01-27 | International Business Machines Corporation | Nano-fluidic field effective device to control DNA transport through the same |
US8715933B2 (en) | 2010-09-27 | 2014-05-06 | Nabsys, Inc. | Assay methods using nicking endonucleases |
WO2012044857A2 (en) * | 2010-09-30 | 2012-04-05 | California Institute Of Technology | Devices and methods for sequencing nucleic acids |
US9089819B2 (en) | 2010-09-30 | 2015-07-28 | California Institute Of Technology | Particulate nanosorting stack |
US9184099B2 (en) | 2010-10-04 | 2015-11-10 | The Board Of Trustees Of The Leland Stanford Junior University | Biosensor devices, systems and methods therefor |
JP6114694B2 (en) | 2010-10-04 | 2017-04-12 | ジナプシス インコーポレイテッド | Systems and methods for automated reusable parallel biological reactions |
EP2640849B1 (en) | 2010-11-16 | 2016-04-06 | Nabsys 2.0 LLC | Methods for sequencing a biomolecule by detecting relative positions of hybridized probes |
WO2012109574A2 (en) | 2011-02-11 | 2012-08-16 | Nabsys, Inc. | Assay methods using dna binding proteins |
US9362568B2 (en) | 2011-02-18 | 2016-06-07 | The Board Of Trustees Of The Leland Stanford Junior University | Battery with hybrid electrocatalysts |
US8558326B2 (en) * | 2011-04-06 | 2013-10-15 | International Business Machines Corporation | Semiconductor devices having nanochannels confined by nanometer-spaced electrodes |
US8585973B2 (en) | 2011-05-27 | 2013-11-19 | The Board Of Trustees Of The Leland Stanford Junior University | Nano-sensor array |
US9926596B2 (en) | 2011-05-27 | 2018-03-27 | Genapsys, Inc. | Systems and methods for genetic and biological analysis |
EP3633370A1 (en) | 2011-05-27 | 2020-04-08 | Oxford Nanopore Technologies Limited | Coupling method |
US20140235474A1 (en) | 2011-06-24 | 2014-08-21 | Sequenom, Inc. | Methods and processes for non invasive assessment of a genetic variation |
KR102023754B1 (en) * | 2011-07-27 | 2019-09-20 | 더 보오드 오브 트러스티스 오브 더 유니버시티 오브 일리노이즈 | Nanopore sensors for biomolecular characterization |
JP5670278B2 (en) * | 2011-08-09 | 2015-02-18 | 株式会社日立ハイテクノロジーズ | Nanopore analyzer |
US8691067B2 (en) * | 2011-09-16 | 2014-04-08 | International Business Machines Corporation | Charged entities as locomotive to control motion of polymers through a nanochannel |
WO2013041878A1 (en) * | 2011-09-23 | 2013-03-28 | Oxford Nanopore Technologies Limited | Analysis of a polymer comprising polymer units |
US10424394B2 (en) | 2011-10-06 | 2019-09-24 | Sequenom, Inc. | Methods and processes for non-invasive assessment of genetic variations |
US9984198B2 (en) | 2011-10-06 | 2018-05-29 | Sequenom, Inc. | Reducing sequence read count error in assessment of complex genetic variations |
US10196681B2 (en) | 2011-10-06 | 2019-02-05 | Sequenom, Inc. | Methods and processes for non-invasive assessment of genetic variations |
CA2850785C (en) | 2011-10-06 | 2022-12-13 | Sequenom, Inc. | Methods and processes for non-invasive assessment of genetic variations |
US9367663B2 (en) | 2011-10-06 | 2016-06-14 | Sequenom, Inc. | Methods and processes for non-invasive assessment of genetic variations |
CN104105797B (en) | 2011-12-01 | 2016-08-31 | 吉纳普赛斯股份有限公司 | System and method for efficent electronic order-checking with detection |
KR101933619B1 (en) | 2011-12-26 | 2018-12-31 | 삼성전자주식회사 | Nanopore device, method of fabricating the same, and DNA detection apparatus including the same |
WO2013109981A1 (en) | 2012-01-20 | 2013-07-25 | Sequenom, Inc. | Diagnostic processes that factor experimental conditions |
CN107828877A (en) * | 2012-01-20 | 2018-03-23 | 吉尼亚科技公司 | Molecular Detection and sequencing based on nano-pore |
US9920361B2 (en) | 2012-05-21 | 2018-03-20 | Sequenom, Inc. | Methods and compositions for analyzing nucleic acid |
US10504613B2 (en) | 2012-12-20 | 2019-12-10 | Sequenom, Inc. | Methods and processes for non-invasive assessment of genetic variations |
US10497461B2 (en) | 2012-06-22 | 2019-12-03 | Sequenom, Inc. | Methods and processes for non-invasive assessment of genetic variations |
WO2014052616A2 (en) | 2012-09-27 | 2014-04-03 | The Trustees Of The University Of Pennsylvania | Insulated nanoelectrode-nanopore devices and related methods |
US10482994B2 (en) | 2012-10-04 | 2019-11-19 | Sequenom, Inc. | Methods and processes for non-invasive assessment of genetic variations |
US9274430B2 (en) | 2012-10-10 | 2016-03-01 | Arizona Board Of Regents On Behalf Of Arizona State University | Systems and devices for molecule sensing and method of manufacturing thereof |
US8906215B2 (en) * | 2012-11-30 | 2014-12-09 | International Business Machines Corporation | Field effect based nanosensor for biopolymer manipulation and detection |
GB201222928D0 (en) | 2012-12-19 | 2013-01-30 | Oxford Nanopore Tech Ltd | Analysis of a polynucleotide |
US9914966B1 (en) | 2012-12-20 | 2018-03-13 | Nabsys 2.0 Llc | Apparatus and methods for analysis of biomolecules using high frequency alternating current excitation |
US10294516B2 (en) | 2013-01-18 | 2019-05-21 | Nabsys 2.0 Llc | Enhanced probe binding |
US20130309666A1 (en) | 2013-01-25 | 2013-11-21 | Sequenom, Inc. | Methods and processes for non-invasive assessment of genetic variations |
EP2965073B1 (en) * | 2013-03-05 | 2018-10-31 | Arizona Board Of Regents Acting For And On Behalf Of State Arizona University | Translocation of a polymer through a nanopore |
US9689829B2 (en) | 2013-03-12 | 2017-06-27 | New Jersey Institute Of Technology | Nanoprobe and methods of use |
EP2971141B1 (en) | 2013-03-15 | 2018-11-28 | Genapsys, Inc. | Systems for biological analysis |
EP2981921B1 (en) | 2013-04-03 | 2023-01-18 | Sequenom, Inc. | Methods and processes for non-invasive assessment of genetic variations |
US10345289B2 (en) * | 2013-04-18 | 2019-07-09 | The Board Of Trustees Of The University Of Illinois | Method and apparatus for analyzing a target material |
US10677752B2 (en) | 2013-04-18 | 2020-06-09 | The Board Of Trustees Of The University Of Illinois | Method and apparatus analyzing a target material |
IL309903A (en) | 2013-05-24 | 2024-03-01 | Sequenom Inc | Methods and processes for non-invasive assessment of genetic variations |
EP3540076A1 (en) | 2013-06-21 | 2019-09-18 | Sequenom, Inc. | Methods and processes for non-invasive assessment of genetic variations |
US10041930B2 (en) * | 2013-06-28 | 2018-08-07 | Globalfoundries Inc. | Tunneling junction to distinguish targeted DNA segment |
IL295860B2 (en) | 2013-10-04 | 2024-01-01 | Sequenom Inc | Methods and processes for non-invasive assessment of genetic variations |
JP6680680B2 (en) | 2013-10-07 | 2020-04-15 | セクエノム, インコーポレイテッド | Methods and processes for non-invasive assessment of chromosomal alterations |
US10125393B2 (en) | 2013-12-11 | 2018-11-13 | Genapsys, Inc. | Systems and methods for biological analysis and computation |
GB201406155D0 (en) | 2014-04-04 | 2014-05-21 | Oxford Nanopore Tech Ltd | Method |
US10336713B2 (en) | 2014-02-27 | 2019-07-02 | Arizona Board Of Regents, Acting For And On Behalf Of, Arizona State University | Triazole-based reader molecules and methods for synthesizing and use thereof |
US9765326B2 (en) * | 2014-04-03 | 2017-09-19 | Stmicroelectronics S.R.L. | Apparatus and method for nucleic acid sequencing based on nanochannels |
US10190161B2 (en) | 2014-04-03 | 2019-01-29 | Stmicroelectronics S.R.L. | Apparatus and method for nucleic acid sequencing based on nanowire detectors |
WO2015150786A1 (en) | 2014-04-04 | 2015-10-08 | Oxford Nanopore Technologies Limited | Method for characterising a double stranded nucleic acid using a nano-pore and anchor molecules at both ends of said nucleic acid |
US10612084B2 (en) | 2014-04-08 | 2020-04-07 | International Business Machines Corporation | Reduction of entropic barrier of polyelectrolyte molecules in a nanopore device with agarose gel |
EP3132060B1 (en) | 2014-04-18 | 2019-03-13 | Genapsys Inc. | Methods and systems for nucleic acid amplification |
US9658184B2 (en) | 2014-05-07 | 2017-05-23 | International Business Machines Corporation | Increasing the capture zone by nanostructure patterns |
US9921181B2 (en) | 2014-06-26 | 2018-03-20 | International Business Machines Corporation | Detection of translocation events using graphene-based nanopore assemblies |
US11783911B2 (en) | 2014-07-30 | 2023-10-10 | Sequenom, Inc | Methods and processes for non-invasive assessment of genetic variations |
CN107109490B (en) | 2014-10-16 | 2022-12-02 | 牛津楠路珀尔科技股份有限公司 | Analysis of polymers |
GB201418469D0 (en) | 2014-10-17 | 2014-12-03 | Oxford Nanopore Tech Ltd | Method |
KR101666725B1 (en) * | 2014-12-18 | 2016-10-17 | 고려대학교 산학협력단 | Nanopore device and method of manufacturing the same |
US9863904B2 (en) | 2014-12-19 | 2018-01-09 | Genia Technologies, Inc. | Nanopore-based sequencing with varying voltage stimulus |
US9557294B2 (en) | 2014-12-19 | 2017-01-31 | Genia Technologies, Inc. | Nanopore-based sequencing with varying voltage stimulus |
BR112017021256A2 (en) | 2015-04-03 | 2018-06-26 | Abbott Laboratories | devices and methods for sample analysis |
CN107690582B (en) | 2015-04-03 | 2023-10-20 | 雅培制药有限公司 | Apparatus and method for sample analysis |
WO2017004463A1 (en) | 2015-07-01 | 2017-01-05 | Abbott Laboratories | Devices and methods for sample analysis |
US10126262B2 (en) | 2015-09-24 | 2018-11-13 | Genia Technologies, Inc. | Differential output of analog memories storing nanopore measurement samples |
EP3368178A4 (en) * | 2015-10-30 | 2019-04-17 | Universal Sequencing Technology Corporation | Methods and systems for controlling dna, rna and other biological molecules passing through nanopores |
CN108473933A (en) | 2015-12-08 | 2018-08-31 | 昆塔波尔公司 | The method for making nucleic acid be shifted through nano-pore |
JP6967006B2 (en) | 2016-01-15 | 2021-11-17 | クアンタポール, インコーポレイテッド | Nanopore analysis based on reduced background optics |
US10859562B2 (en) | 2016-02-29 | 2020-12-08 | Iridia, Inc. | Methods, compositions, and devices for information storage |
US10640822B2 (en) | 2016-02-29 | 2020-05-05 | Iridia, Inc. | Systems and methods for writing, reading, and controlling data stored in a polymer |
US10438662B2 (en) | 2016-02-29 | 2019-10-08 | Iridia, Inc. | Methods, compositions, and devices for information storage |
JP2019517252A (en) | 2016-05-31 | 2019-06-24 | クアンタポール, インコーポレイテッド | Two-color nanopore sequencing |
EP3488017A4 (en) | 2016-07-20 | 2020-02-26 | Genapsys Inc. | Systems and methods for nucleic acid sequencing |
WO2018022890A1 (en) | 2016-07-27 | 2018-02-01 | Sequenom, Inc. | Genetic copy number alteration classifications |
CN109804087A (en) | 2016-08-19 | 2019-05-24 | 昆塔波尔公司 | Using quencher based on optical nano-pore sequencing |
CN109863391B (en) | 2016-10-05 | 2021-11-05 | 雅培实验室 | Device and method for sample analysis |
EP3574424A1 (en) | 2017-01-24 | 2019-12-04 | Sequenom, Inc. | Methods and processes for assessment of genetic variations |
MX2020003113A (en) | 2017-09-21 | 2020-09-07 | Genapsys Inc | Systems and methods for nucleic acid sequencing. |
US11049727B2 (en) | 2019-06-03 | 2021-06-29 | International Business Machines Corporation | Interleaved structure for molecular manipulation |
US11738995B2 (en) | 2019-06-21 | 2023-08-29 | International Business Machines Corporation | Manipulation of a molecule using dipole moments |
US11837302B1 (en) | 2020-08-07 | 2023-12-05 | Iridia, Inc. | Systems and methods for writing and reading data stored in a polymer using nano-channels |
Citations (10)
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 |
US20030141189A1 (en) * | 2002-01-28 | 2003-07-31 | Lee James W. | DNA and RNA sequencing by nanoscale reading through programmable electrophoresis and nanoelectrode-gated tunneling and dielectric detection |
US6627067B1 (en) * | 1999-06-22 | 2003-09-30 | President And Fellows Of Harvard College | Molecular and atomic scale evaluation of biopolymers |
US20040011650A1 (en) * | 2002-07-22 | 2004-01-22 | Frederic Zenhausern | Method and apparatus for manipulating polarizable analytes via dielectrophoresis |
US20060019259A1 (en) * | 2004-07-22 | 2006-01-26 | Joyce Timothy H | Characterization of biopolymers by resonance tunneling and fluorescence quenching |
US20060057585A1 (en) * | 2004-09-10 | 2006-03-16 | Mcallister William H | Nanostepper/sensor systems and methods of use thereof |
US20060063171A1 (en) * | 2004-03-23 | 2006-03-23 | Mark Akeson | Methods and apparatus for characterizing polynucleotides |
US20060068401A1 (en) * | 2004-09-30 | 2006-03-30 | Flory Curt A | Biopolymer resonant tunneling with a gate voltage source |
US7279337B2 (en) * | 2004-03-10 | 2007-10-09 | Agilent Technologies, Inc. | Method and apparatus for sequencing polymers through tunneling conductance variation detection |
US7468271B2 (en) * | 2005-04-06 | 2008-12-23 | President And Fellows Of Harvard College | Molecular characterization with carbon nanotube control |
Family Cites Families (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US6193866B1 (en) | 1996-03-27 | 2001-02-27 | Curagen Corporation | Separation of charged particles by a spatially and temporally varying electric field |
AU2001259128A1 (en) | 2000-04-24 | 2001-11-07 | Eagle Research And Development, Llc | An ultra-fast nucleic acid sequencing device and a method for making and using the same |
US7786086B2 (en) * | 2004-09-08 | 2010-08-31 | Ramot At Tel-Aviv University Ltd. | Peptide nanostructures containing end-capping modified peptides and methods of generating and using the same |
US8003319B2 (en) | 2007-02-02 | 2011-08-23 | International Business Machines Corporation | Systems and methods for controlling position of charged polymer inside nanopore |
-
2007
- 2007-02-02 US US11/670,621 patent/US8003319B2/en active Active
-
2008
- 2008-01-18 WO PCT/EP2008/050562 patent/WO2008092760A1/en active Application Filing
- 2008-01-18 CA CA2708782A patent/CA2708782A1/en not_active Abandoned
- 2008-01-18 EP EP08701574.9A patent/EP2109685B1/en not_active Not-in-force
-
2009
- 2009-08-13 US US12/540,553 patent/US20100025249A1/en not_active Abandoned
Patent Citations (10)
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 |
US6627067B1 (en) * | 1999-06-22 | 2003-09-30 | President And Fellows Of Harvard College | Molecular and atomic scale evaluation of biopolymers |
US20030141189A1 (en) * | 2002-01-28 | 2003-07-31 | Lee James W. | DNA and RNA sequencing by nanoscale reading through programmable electrophoresis and nanoelectrode-gated tunneling and dielectric detection |
US20040011650A1 (en) * | 2002-07-22 | 2004-01-22 | Frederic Zenhausern | Method and apparatus for manipulating polarizable analytes via dielectrophoresis |
US7279337B2 (en) * | 2004-03-10 | 2007-10-09 | Agilent Technologies, Inc. | Method and apparatus for sequencing polymers through tunneling conductance variation detection |
US20060063171A1 (en) * | 2004-03-23 | 2006-03-23 | Mark Akeson | Methods and apparatus for characterizing polynucleotides |
US20060019259A1 (en) * | 2004-07-22 | 2006-01-26 | Joyce Timothy H | Characterization of biopolymers by resonance tunneling and fluorescence quenching |
US20060057585A1 (en) * | 2004-09-10 | 2006-03-16 | Mcallister William H | Nanostepper/sensor systems and methods of use thereof |
US20060068401A1 (en) * | 2004-09-30 | 2006-03-30 | Flory Curt A | Biopolymer resonant tunneling with a gate voltage source |
US7468271B2 (en) * | 2005-04-06 | 2008-12-23 | President And Fellows Of Harvard College | Molecular characterization with carbon nanotube control |
Cited By (108)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US8889348B2 (en) | 2006-06-07 | 2014-11-18 | The Trustees Of Columbia University In The City Of New York | DNA sequencing by nanopore using modified nucleotides |
US20090298072A1 (en) * | 2006-06-07 | 2009-12-03 | The Trustees Of Columbia University In The City Of | DNA Sequencing by Nanopore Using Modified Nucleotides |
US9903820B2 (en) | 2007-05-08 | 2018-02-27 | The Trustees Of Boston University | Chemical functionalization of solid-state nanopores and nanopore arrays and applications thereof |
US11002724B2 (en) | 2007-05-08 | 2021-05-11 | Trustees Of Boston University | Chemical functionalization of solid-state nanopores and nanopore arrays and applications thereof |
US10101315B2 (en) | 2007-05-08 | 2018-10-16 | Trustees Of Boston University | Chemical functionalization of solid-state nanopores and nanopore arrays and applications thereof |
US9738927B2 (en) | 2009-05-12 | 2017-08-22 | Daniel Wai-Cheong So | Method and apparatus for the analysis and identification of molecules |
US8926904B2 (en) | 2009-05-12 | 2015-01-06 | Daniel Wai-Cheong So | Method and apparatus for the analysis and identification of molecules |
US9279153B2 (en) | 2009-09-30 | 2016-03-08 | Quantapore, Inc. | Ultrafast sequencing of biological polymers using a labeled nanopore |
US8771491B2 (en) | 2009-09-30 | 2014-07-08 | Quantapore, Inc. | Ultrafast sequencing of biological polymers using a labeled nanopore |
US10343350B2 (en) | 2010-02-08 | 2019-07-09 | Genia Technologies, Inc. | Systems and methods for forming a nanopore in a lipid bilayer |
US9678055B2 (en) | 2010-02-08 | 2017-06-13 | Genia Technologies, Inc. | Methods for forming a nanopore in a lipid bilayer |
US11027502B2 (en) | 2010-02-08 | 2021-06-08 | Roche Sequencing Solutions, Inc. | Systems and methods for forming a nanopore in a lipid bilayer |
US8324914B2 (en) * | 2010-02-08 | 2012-12-04 | Genia Technologies, Inc. | Systems and methods for characterizing a molecule |
US9605307B2 (en) | 2010-02-08 | 2017-03-28 | Genia Technologies, Inc. | Systems and methods for forming a nanopore in a lipid bilayer |
US10926486B2 (en) | 2010-02-08 | 2021-02-23 | Roche Sequencing Solutions, Inc. | Systems and methods for forming a nanopore in a lipid bilayer |
US10371692B2 (en) | 2010-02-08 | 2019-08-06 | Genia Technologies, Inc. | Systems for forming a nanopore in a lipid bilayer |
US9041420B2 (en) | 2010-02-08 | 2015-05-26 | Genia Technologies, Inc. | Systems and methods for characterizing a molecule |
US20110193570A1 (en) * | 2010-02-08 | 2011-08-11 | Genia Technologies, Inc. | Systems and methods for characterizing a molecule |
US20110201204A1 (en) * | 2010-02-12 | 2011-08-18 | International Business Machines Corporation | Precisely Tuning Feature Sizes on Hard Masks Via Plasma Treatment |
US8084319B2 (en) | 2010-02-12 | 2011-12-27 | International Business Machines Corporation | Precisely tuning feature sizes on hard masks via plasma treatment |
US9194838B2 (en) | 2010-03-03 | 2015-11-24 | Osaka University | Method and device for identifying nucleotide, and method and device for determining nucleotide sequence of polynucleotide |
US10876159B2 (en) | 2010-03-03 | 2020-12-29 | Quantum Biosystems Inc. | Method and device for identifying nucleotide, and method and device for determining nucleotide sequence of polynucleotide |
US10202644B2 (en) | 2010-03-03 | 2019-02-12 | Quantum Biosystems Inc. | Method and device for identifying nucleotide, and method and device for determining nucleotide sequence of polynucleotide |
US20110223652A1 (en) * | 2010-03-15 | 2011-09-15 | International Business Machines Corporation | Piezoelectric-based nanopore device for the active control of the motion of polymers through the same |
WO2011115709A1 (en) * | 2010-03-15 | 2011-09-22 | International Business Machines Corp. | Nanopore based device for cutting long dna molecules into fragments |
US8039250B2 (en) | 2010-03-15 | 2011-10-18 | International Business Machines Corporation | Piezoelectric-based nanopore device for the active control of the motion of polymers through the same |
GB2511720A (en) * | 2010-03-15 | 2014-09-17 | Ibm | Nanopore based device for cutting long DNA molecules into fragments |
US8641877B2 (en) | 2010-03-15 | 2014-02-04 | International Business Machines Corporation | Nanopore based device for cutting long DNA molecules into fragments |
TWI510614B (en) * | 2010-03-15 | 2015-12-01 | Ibm | Nanopore based device for cutting long dna molecules into fragments |
US20110224098A1 (en) * | 2010-03-15 | 2011-09-15 | International Business Machines Corporation | Nanopore Based Device for Cutting Long DNA Molecules into Fragments |
DE112011100919B4 (en) * | 2010-03-15 | 2013-08-08 | International Business Machines Corp. | Nanopore unit for cutting long DNA molecules into fragments |
US8603303B2 (en) | 2010-03-15 | 2013-12-10 | International Business Machines Corporation | Nanopore based device for cutting long DNA molecules into fragments |
US8598018B2 (en) | 2010-06-22 | 2013-12-03 | International Business Machines Corporation | Forming an electrode having reduced corrosion and water decomposition on surface using a custom oxide layer |
US8354336B2 (en) | 2010-06-22 | 2013-01-15 | International Business Machines Corporation | Forming an electrode having reduced corrosion and water decomposition on surface using an organic protective layer |
US11499186B2 (en) | 2010-12-17 | 2022-11-15 | The Trustees Of Columbia University In The City Of New York | DNA sequencing by synthesis using modified nucleotides and nanopore detection |
US10443096B2 (en) | 2010-12-17 | 2019-10-15 | The Trustees Of Columbia University In The City Of New York | DNA sequencing by synthesis using modified nucleotides and nanopore detection |
US8845880B2 (en) | 2010-12-22 | 2014-09-30 | Genia Technologies, Inc. | Nanopore-based single DNA molecule characterization, identification and isolation using speed bumps |
US9121059B2 (en) | 2010-12-22 | 2015-09-01 | Genia Technologies, Inc. | Nanopore-based single molecule characterization |
US10920271B2 (en) | 2010-12-22 | 2021-02-16 | Roche Sequencing Solutions, Inc. | Nanopore-based single DNA molecule characterization, identification and isolation using speed bumps |
US10400278B2 (en) | 2010-12-22 | 2019-09-03 | Genia Technologies, Inc. | Nanopore-based single DNA molecule characterization, identification and isolation using speed bumps |
US9617593B2 (en) | 2010-12-22 | 2017-04-11 | Genia Technologies, Inc. | Nanopore-based single DNA molecule characterization, identification and isolation using speed bumps |
US9581563B2 (en) | 2011-01-24 | 2017-02-28 | Genia Technologies, Inc. | System for communicating information from an array of sensors |
US10156541B2 (en) | 2011-01-24 | 2018-12-18 | Genia Technologies, Inc. | System for detecting electrical properties of a molecular complex |
US8962242B2 (en) | 2011-01-24 | 2015-02-24 | Genia Technologies, Inc. | System for detecting electrical properties of a molecular complex |
US9110478B2 (en) | 2011-01-27 | 2015-08-18 | Genia Technologies, Inc. | Temperature regulation of measurement arrays |
US10010852B2 (en) | 2011-01-27 | 2018-07-03 | Genia Technologies, Inc. | Temperature regulation of measurement arrays |
US8986524B2 (en) | 2011-01-28 | 2015-03-24 | International Business Machines Corporation | DNA sequence using multiple metal layer structure with different organic coatings forming different transient bondings to DNA |
US8858764B2 (en) | 2011-01-28 | 2014-10-14 | International Business Machines Corporation | Electron beam sculpting of tunneling junction for nanopore DNA sequencing |
US8852407B2 (en) | 2011-01-28 | 2014-10-07 | International Business Machines Corporation | Electron beam sculpting of tunneling junction for nanopore DNA sequencing |
US9285339B2 (en) | 2011-01-28 | 2016-03-15 | International Business Machines Corporation | DNA sequencing using multiple metal layer structure with different organic coatings forming different transient bondings to DNA |
US8764968B2 (en) | 2011-01-28 | 2014-07-01 | International Business Machines Corporation | DNA sequencing using multiple metal layer structure with organic coatings forming transient bonding to DNA bases |
US9513277B2 (en) | 2011-01-28 | 2016-12-06 | International Business Machines Corporation | DNA sequencing using multiple metal layer structure with different organic coatings forming different transient bondings to DNA |
US10267784B2 (en) | 2011-01-28 | 2019-04-23 | International Business Machines Corporation | DNA sequencing using multiple metal layer structure with different organic coatings forming different transient bondings to DNA |
GB2510484B (en) * | 2011-06-17 | 2019-08-28 | Ibm | Nanopore-based molecular dispensers |
GB2510484A (en) * | 2011-06-17 | 2014-08-06 | Ibm | Molecular Dispensers |
KR101581099B1 (en) * | 2011-06-17 | 2015-12-29 | 인터내셔널 비지네스 머신즈 코포레이션 | Molecular dispensers |
US8546080B2 (en) | 2011-06-17 | 2013-10-01 | International Business Machines Corporation | Molecular dispensers |
US8574894B2 (en) | 2011-06-17 | 2013-11-05 | International Business Machines Corporation | Molecular dispensers |
CN103562138A (en) * | 2011-06-17 | 2014-02-05 | 国际商业机器公司 | Molecular dispensers |
KR20140007936A (en) * | 2011-06-17 | 2014-01-20 | 인터내셔널 비지네스 머신즈 코포레이션 | Molecular dispensers |
WO2012173723A1 (en) * | 2011-06-17 | 2012-12-20 | International Business Machines Corp. | Molecular dispensers |
WO2013035064A1 (en) * | 2011-09-09 | 2013-03-14 | International Business Machines Corporation | Embedding nanotube inside nanopore for dna translocation |
US11275052B2 (en) | 2012-02-27 | 2022-03-15 | Roche Sequencing Solutions, Inc. | Sensor circuit for controlling, detecting, and measuring a molecular complex |
US8986629B2 (en) | 2012-02-27 | 2015-03-24 | Genia Technologies, Inc. | Sensor circuit for controlling, detecting, and measuring a molecular complex |
US10029915B2 (en) | 2012-04-04 | 2018-07-24 | International Business Machines Corporation | Functionally switchable self-assembled coating compound for controlling translocation of molecule through nanopores |
US10040682B2 (en) | 2012-04-04 | 2018-08-07 | International Business Machines Corporation | Functionally switchable self-assembled coating compound for controlling translocation of molecule through nanopores |
US10246479B2 (en) | 2012-04-09 | 2019-04-02 | The Trustees Of Columbia University In The City Of New York | Method of preparation of nanopore and uses thereof |
US11795191B2 (en) | 2012-04-09 | 2023-10-24 | The Trustees Of Columbia University In The City Of New York | Method of preparation of nanopore and uses thereof |
US9494554B2 (en) | 2012-06-15 | 2016-11-15 | Genia Technologies, Inc. | Chip set-up and high-accuracy nucleic acid sequencing |
US9535033B2 (en) | 2012-08-17 | 2017-01-03 | Quantum Biosystems Inc. | Sample analysis method |
US9651539B2 (en) | 2012-10-28 | 2017-05-16 | Quantapore, Inc. | Reducing background fluorescence in MEMS materials by low energy ion beam treatment |
US10526647B2 (en) | 2012-11-09 | 2020-01-07 | The Trustees Of Columbia University In The City Of New York | Nucleic acid sequences using tags |
US9605309B2 (en) | 2012-11-09 | 2017-03-28 | Genia Technologies, Inc. | Nucleic acid sequencing using tags |
US11674174B2 (en) | 2012-11-09 | 2023-06-13 | The Trustees Of Columbia University In The City Of New York | Nucleic acid sequences using tags |
US10822650B2 (en) | 2012-11-09 | 2020-11-03 | Roche Sequencing Solutions, Inc. | Nucleic acid sequencing using tags |
US9506894B2 (en) | 2012-12-27 | 2016-11-29 | Quantum Biosystems Inc. | Method for controlling substance moving speed and apparatus for controlling the same |
US10012637B2 (en) | 2013-02-05 | 2018-07-03 | Genia Technologies, Inc. | Nanopore arrays |
US9759711B2 (en) | 2013-02-05 | 2017-09-12 | Genia Technologies, Inc. | Nanopore arrays |
US10809244B2 (en) | 2013-02-05 | 2020-10-20 | Roche Sequencing Solutions, Inc. | Nanopore arrays |
US20160025702A1 (en) * | 2013-03-13 | 2016-01-28 | Arizona Board Of Regents On Behalf Of Arizona State University | Systems, devices and methods for translocation control |
US10732183B2 (en) | 2013-03-15 | 2020-08-04 | The Trustees Of Columbia University In The City Of New York | Method for detecting multiple predetermined compounds in a sample |
US9046511B2 (en) | 2013-04-18 | 2015-06-02 | International Business Machines Corporation | Fabrication of tunneling junction for nanopore DNA sequencing |
US9222930B2 (en) | 2013-04-18 | 2015-12-29 | Globalfoundries Inc. | Fabrication of tunneling junction for nanopore DNA sequencing |
US9862997B2 (en) | 2013-05-24 | 2018-01-09 | Quantapore, Inc. | Nanopore-based nucleic acid analysis with mixed FRET detection |
US9097698B2 (en) | 2013-06-19 | 2015-08-04 | International Business Machines Corporation | Nanogap device with capped nanowire structures |
US9188578B2 (en) | 2013-06-19 | 2015-11-17 | Globalfoundries Inc. | Nanogap device with capped nanowire structures |
US9182369B2 (en) | 2013-06-19 | 2015-11-10 | Globalfoundries Inc. | Manufacturable sub-3 nanometer palladium gap devices for fixed electrode tunneling recognition |
US9128078B2 (en) | 2013-06-19 | 2015-09-08 | International Business Machines Corporation | Manufacturable sub-3 nanometer palladium gap devices for fixed electrode tunneling recognition |
EP3578987A1 (en) | 2013-09-18 | 2019-12-11 | Quantum Biosystems Inc. | Biomolecule sequencing devices, systems and methods |
US10557167B2 (en) | 2013-09-18 | 2020-02-11 | Quantum Biosystems Inc. | Biomolecule sequencing devices, systems and methods |
US9644236B2 (en) | 2013-09-18 | 2017-05-09 | Quantum Biosystems Inc. | Biomolecule sequencing devices, systems and methods |
US10261066B2 (en) | 2013-10-16 | 2019-04-16 | Quantum Biosystems Inc. | Nano-gap electrode pair and method of manufacturing same |
US10466228B2 (en) | 2013-10-16 | 2019-11-05 | Quantum Biosystems Inc. | Nano-gap electrode pair and method of manufacturing same |
US9551697B2 (en) | 2013-10-17 | 2017-01-24 | Genia Technologies, Inc. | Non-faradaic, capacitively coupled measurement in a nanopore cell array |
US10393700B2 (en) | 2013-10-17 | 2019-08-27 | Roche Sequencing Solutions, Inc. | Non-faradaic, capacitively coupled measurement in a nanopore cell array |
US10421995B2 (en) | 2013-10-23 | 2019-09-24 | Genia Technologies, Inc. | High speed molecular sensing with nanopores |
US9567630B2 (en) | 2013-10-23 | 2017-02-14 | Genia Technologies, Inc. | Methods for forming lipid bilayers on biochips |
US9322062B2 (en) | 2013-10-23 | 2016-04-26 | Genia Technologies, Inc. | Process for biosensor well formation |
US11021745B2 (en) | 2013-10-23 | 2021-06-01 | Roche Sequencing Solutions, Inc. | Methods for forming lipid bilayers on biochips |
US11396677B2 (en) | 2014-03-24 | 2022-07-26 | The Trustees Of Columbia University In The City Of New York | Chemical methods for producing tagged nucleotides |
US10438811B1 (en) | 2014-04-15 | 2019-10-08 | Quantum Biosystems Inc. | Methods for forming nano-gap electrodes for use in nanosensors |
US10597712B2 (en) | 2014-10-10 | 2020-03-24 | Quantapore, Inc. | Nanopore-based polymer analysis with mutually-quenching fluorescent labels |
US9885079B2 (en) | 2014-10-10 | 2018-02-06 | Quantapore, Inc. | Nanopore-based polymer analysis with mutually-quenching fluorescent labels |
US11041197B2 (en) | 2014-10-24 | 2021-06-22 | Quantapore, Inc. | Efficient optical analysis of polymers using arrays of nanostructures |
US9624537B2 (en) | 2014-10-24 | 2017-04-18 | Quantapore, Inc. | Efficient optical analysis of polymers using arrays of nanostructures |
US20160194698A1 (en) * | 2014-12-16 | 2016-07-07 | Arizona Board Of Regents On Behalf Of Arizona State University | Systems, apparatuses and methods for reading polymer sequence |
US10823721B2 (en) | 2016-07-05 | 2020-11-03 | Quantapore, Inc. | Optically based nanopore sequencing |
US11565258B2 (en) | 2016-10-03 | 2023-01-31 | Genvida Technology Company Limited | Method and apparatus for the analysis and identification of molecules |
Also Published As
Publication number | Publication date |
---|---|
US8003319B2 (en) | 2011-08-23 |
CA2708782A1 (en) | 2008-08-07 |
WO2008092760A1 (en) | 2008-08-07 |
US20080187915A1 (en) | 2008-08-07 |
EP2109685B1 (en) | 2014-10-15 |
EP2109685A1 (en) | 2009-10-21 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
US8003319B2 (en) | Systems and methods for controlling position of charged polymer inside nanopore | |
US10495628B2 (en) | Multiplexed biomarker quantitation by nanopore analysis of biomarker-polymer complexes | |
US9528152B2 (en) | DNA sequencing methods and detectors and systems for carrying out the same | |
US20200348293A1 (en) | Target Detection with Nanopore | |
US7947485B2 (en) | Method and apparatus for molecular analysis using nanoelectronic circuits | |
US8273532B2 (en) | Capture, recapture, and trapping of molecules with a nanopore | |
US7410564B2 (en) | Apparatus and method for biopolymer identification during translocation through a nanopore | |
US20060275779A1 (en) | Method and apparatus for molecular analysis using nanowires | |
US20070178507A1 (en) | Method and apparatus for detection of molecules using nanopores | |
US8999130B2 (en) | Field effect based nanosensor for biopolymer manipulation and detection | |
EP2734840B1 (en) | Dual-pore device | |
KR20160130380A (en) | Devices, systems and methods for sequencing biomolecules | |
WO2017087908A1 (en) | Nanochannel devices and methods for analysis of molecules | |
US20050202446A1 (en) | Methods for biopolymer sequencing using metal inclusions | |
US20130252235A1 (en) | Mobility Controlled Single Macromolecule in Nanofluidic System and its Application as Macromolecule Sequencer | |
JP2024512838A (en) | Scalable circuit for molecular detection | |
Ding et al. | Wednesday, March 4, 2009 647a |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
AS | Assignment |
Owner name: GLOBALFOUNDRIES U.S. 2 LLC, NEW YORK Free format text: ASSIGNMENT OF ASSIGNORS INTEREST;ASSIGNOR:INTERNATIONAL BUSINESS MACHINES CORPORATION;REEL/FRAME:036550/0001 Effective date: 20150629 |
|
AS | Assignment |
Owner name: GLOBALFOUNDRIES INC., CAYMAN ISLANDS Free format text: ASSIGNMENT OF ASSIGNORS INTEREST;ASSIGNORS:GLOBALFOUNDRIES U.S. 2 LLC;GLOBALFOUNDRIES U.S. INC.;REEL/FRAME:036779/0001 Effective date: 20150910 |
|
STCB | Information on status: application discontinuation |
Free format text: ABANDONED -- AFTER EXAMINER'S ANSWER OR BOARD OF APPEALS DECISION |
|
AS | Assignment |
Owner name: GLOBALFOUNDRIES U.S. INC., NEW YORK Free format text: RELEASE BY SECURED PARTY;ASSIGNOR:WILMINGTON TRUST, NATIONAL ASSOCIATION;REEL/FRAME:056987/0001 Effective date: 20201117 |