# US 2014/0154790 A1 · Biomolecule information analysis device

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- Number: US 2014/0154790 A1
- Document ID: US20140154790A1
- Status: Published application
- Kind: A1
- Application number: 14/122,206
- Filed: 2011-05-31
- Published: 2014-06-05
- Earliest claimed: 2011-05-31
- Assignees: Hitachi, Ltd.
- Applicants: Hitachi, Ltd.
- Inventors: Kazuo Ono; Tatsuo Nakagawa; Yoshimitsu Yanagawa; Takayuki Kawahara; Akira Kotabe; Riichiro Takemura
- Web page: https://patentgrep.com/patent/US20140154790A1

## CPC

- C12Q 1/68: involving nucleic acids
- C12Q 1/6869: Methods for sequencing
- G01N 33/48721: {Investigating individual macromolecules, e.g. by translocation through nanopores (Coulter counters in general G01N15/12; fabrication methods for nanoscale apertures B81B1/00; sequencing of nucleic acids C12Q1/68)}
- C12Q: MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS (immunoassay G01N33/53); COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
- G01N: INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES (measuring or testing apparatus or processes other than immunoassay, involving enzymes or microorganisms C12M, C12Q)

## Abstract

Provided is a device that, on the basis of a measurement result of a current that has a low value and a wide distribution, identifies the composition of biological molecules passing through a nanoparticle path. This biomolecule information analysis device obtains a current value by applying an electrical field to biomolecules passing through a gap between a first electrode and a second electrode, and identifies the structure of the biomolecules by integrating the current value and making a comparison with a reference value (see FIG. 1).

## Claims

### Claim 1

A biomolecule information analysis apparatus, comprising:
a first and a second electrodes forming a molecule path through which a biomolecule passes;
an electric voltage application circuit that applies an electric voltage to the first and the second electrodes when the biomolecule passes through the molecule path;
an integration circuit that integrates an electric current caused to flow by an application of an electric voltage by the electric voltage application circuit to the first and the second electrodes; and
a comparison circuit that identifies a structure of the biomolecule by comparing an integration result of the integration circuit with a predetermined reference value.

### Claim 2 (depends on 1)

The biomolecule information analysis apparatus according to claim 1, wherein:
the integration circuit outputs a plurality of the integration result that are different for each of types of molecules constructing the biomolecule after a predetermined duration has passed from starting the integration;
the comparison circuit acquires the integration result of the integration circuit at a time point after the predetermined duration has passed from when the integration circuit started the integration; and
the comparison circuit identifies a type of a molecule constructing the biomolecule according to a number of the integration result exceeding the reference value.

### Claim 3 (depends on 1)

The biomolecule information analysis apparatus according to claim 1, wherein:
the biomolecule is a DNA molecule;
the molecule path includes a first molecule path through which a chain among two chains forming the DNA molecule passes and a second molecule path through which another chain among the two chains of the DNA molecule passes;
the integration circuit performs the integration for each of the DNA molecule passing through the first molecule path and the DNA molecule passing through the second molecule path; and
the comparison circuit identifies a base of the DNA molecule passing through the first molecule path and a base of the DNA molecule passing through the second molecule path respectively by comparing the integration result of the integration circuit with the reference value for each of the DNA molecule passing through the first molecule path and the DNA molecule passing through the second molecule path respectively.

### Claim 4 (depends on 3)

The biomolecule information analysis apparatus according to claim 3, wherein:
the comparison circuit identifies a base of the DNA molecule passing through any one of the first or the second molecule path and then identifies another base by specifying a base which is a complementary pair of the identified base.

### Claim 5 (depends on 1)

The biomolecule information analysis apparatus according to claim 1, further comprising a logarithm conversion circuit that outputs an electric voltage value proportional to a logarithm of the integration result of the integration circuit, wherein:
the comparison circuit compares an output of the logarithm conversion circuit with the reference value.

### Claim 6 (depends on 1)

The biomolecule information analysis apparatus according to claim 1, further comprising a capacitor that connects the first and the second electrodes with the integration circuit by a capacitive coupling.

### Claim 7 (depends on 1)

The biomolecule information analysis apparatus according to claim 1, further comprising:
a memory that stores the integration result of the integration circuit; and
a circuit that adjusts the reference value using the integration result stored in the memory.

### Claim 8 (depends on 1)

The biomolecule information analysis apparatus according to claim 1, further comprising a calibration circuit that calibrates electric currents outputted from the first and the second electrodes;
wherein:
the integration circuit performs the integration before the biomolecule passes through the molecule path, and the integration circuit stores the integration result into the memory; and
the calibration circuit calibrates, using the integration result stored in the memory, the integration result performed by the integration circuit after the biomolecule passes through the molecule path.

### Claim 9 (depends on 1)

The biomolecule information analysis apparatus according to claim 1, further comprising:
a third and a fourth electrodes forming the molecule path in conjunction with the first and the second electrodes; and
a control circuit that controls the third and the fourth electrodes;
wherein:
the control circuit adjusts an electric field applied to the biomolecule passing through the molecule path by adjusting an electric voltage applied to the third and the fourth electrodes; and
the control circuit controls a motion of the biomolecule within the molecule path using the adjusted electric field.

### Claim 10 (depends on 1)

The biomolecule information analysis apparatus according to claim 1, wherein:
a plurality of the first and the second electrodes are disposed along the molecule path; and
at least one of an electrode pair formed by the first and the second electrodes is different in thickness from other pair of the first and the second electrodes.

### Claim 11 (depends on 1)

The biomolecule information analysis apparatus according to claim 1, wherein:
a material reacting to the biomolecule passing through the molecule path is attached to the first and the second electrodes.

### Claim 12 (depends on 11)

The biomolecule information analysis apparatus according to claim 11, wherein:
a plurality of the first and the second electrodes are disposed along the molecule path; and
the material attached to at least one of electrode pairs formed by the first and the second electrodes is different from the material attached to other pair of the first and the second electrodes.

### Claim 13 (depends on 1)

The biomolecule information analysis apparatus according to claim 1, wherein:
a molecule path substrate on which the first and the electrodes are formed is configured to be removable from the biomolecule information analysis apparatus.

### Claim 14 (depends on 13)

The biomolecule information analysis apparatus according to claim 13, further comprising a storage unit that stores an identifier identifying a molecule path substrate on which the first and the second electrodes are formed.

### Claim 15 (depends on 1)

The biomolecule information analysis apparatus according to claim 1, wherein:
the biomolecule is any one of DNA bases coupled in a form of chain.
