JP2015108590A - Measurement unit, analyzer and analysis method - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide an analyzer capable of detecting and analyzing a polymer with high throughput and a high spatial resolution, a measurement unit used for the analyzer, and an analysis method.SOLUTION: The measurement unit for the analyzer comprises: a first thin film including a first opening; and a second thin film including a second opening which is connected with the first opening and has a larger diameter than that of the first opening. Around the second opening, an FET structure is provided which includes a source electrode, a drain electrode and a channel. This measurement unit is used to detect a potential change in the vicinity of the FET structure with partial closing of the first opening caused by a measurement object.

Description

  The present invention relates to an apparatus for analyzing by passing a polymer through a nanopore, a measurement unit used in the apparatus, and an analysis method.

  The nanopore type analyzer is an analyzer that electrically detects a polymer by passing a polymer such as nucleic acid or protein through the nanopore. A blocking current method is known as a detection method of a nanopore analyzer (Non-Patent Document 1). As a specific detection method, first, a thin film having nanopores is placed between two solution tanks. By applying a potential gradient between the solution tanks, ions of the solution contained in the solution tank move in the nanopore, and an ionic current is generated. Next, when a charged polymer is added to one solution tank, the polymer passes through the nanopore due to a potential gradient. When the polymer passes through the inside of the nanopore, the movement of ions inside the nanopore is partially blocked, so that the current value decreases. This is a method for detecting a polymer by reducing the current value.

  In order to improve measurement throughput, parallel nanopores are required. However, in the blocking current method, it is necessary to prevent the mixing of signals between the nanopores by providing a partition between the nanopores of at least one solution tank and isolating the solution between the nanopores. Since partition walls are required between the nanopores, it is difficult to highly integrate the nanopores.

  When a nanopore type analyzer using a blocking current method is used as a DNA sequencer, base identification and sequence decoding are performed by detecting the difference in the blocking current amount of the four bases when DNA passes through the nanopore.

  Further, as a detection method other than the blocking current method, a method of detecting a potential change in the vicinity of the nanopore opening end when a polymer passes through the nanopore is also known (Patent Document 1, Non-Patent Document 2). An apparatus for carrying out this method includes, as constituent elements, two solution tanks, a thin film having nanopores, an electrode for applying a potential gradient between the solution tanks, and a field effect transistor for measuring the potential in the vicinity of the nanopore opening end ( Field effect transistor (FET) structure. The polymer closes the inside of the nanopore, so that the potential near the open end changes. This potential change is detected by the FET structure. Since the polymer is detected based on the electric potential, it is possible to detect a signal independently for each nanopore without isolating the solution between the nanopores. Therefore, a partition between nanopores is unnecessary and high integration is easy.

  Non-Patent Document 2 (FIG. 3c) shows the calculated value of potential change in the vicinity of the nanopore due to the passage of double-stranded DNA through the nanopore, and the salt concentration of the solution on the polymer introduction side is 100 times that on the derivation side. In this case, the potential change is maximum. Non-Patent Document 2 (FIG. 1a) shows that an FET signal accompanying the passage of double-stranded DNA cannot be detected when the salt concentration is the same in the solution on the polymer introduction side and the solution on the delivery side. ing. Therefore, in order to detect the polymer with high sensitivity, it is necessary to make the salt concentration of the solution on the polymer introduction side higher than that on the derivation side.

  However, when the salt concentration on the introduction side of the polymer is increased, the conductivity on the introduction side is increased and the potential change is reduced. Thereby, the electric field near the nanopore opening end on the introduction side becomes weak (Non-patent Document 2, Supplementary FIGS. 5c, d). As a result, since the force for introducing the polymer into the nanopore is weaker than before the gradient of the salt concentration is provided, there is a problem that the frequency of the polymer passing through the nanopore is reduced and the measurement throughput is reduced.

US Patent Application Publication No. 2010/0327847

NANO LETTERS 2010, Vol. 10, pp. 2915-2922 Nature Nanotechnology 2011, Vol. 7, pp. 119-25

  The spatial resolution of the nanopore analyzer depends on the length of the nanopore (the length in the passing direction of the measurement target). For example, when a nanopore analyzer is used as a DNA sequencer, it is necessary to determine the sequence for each base, and it is desirable to obtain a spatial resolution for one base. In order to reduce the spatial resolution to one base, the length of the site blocked by DNA needs to be one base (0.34 nm) or less. In Patent Document 1 (FIG. 1), nanopores are formed in a laminated portion of a thin film (substrate) and an electrode. Therefore, the length of the nanopore is obtained by adding the thickness of the electrode to the thickness of the thin film, and it is difficult to shorten the length of the nanopore.

  Moreover, in patent document 1 (FIG. 2C), although the nanopore is formed in the thin film adjacent to an electrode, there is no structure which supports a thin film in the nanopore vicinity. Therefore, it is difficult to produce a thinner thin film and shorten the length of the nanopore. Therefore, it is difficult to sufficiently improve the spatial resolution with the configuration disclosed in Patent Document 1.

  An object of the present invention is to provide an analyzer capable of detecting and analyzing a polymer with high throughput and high spatial resolution, a measurement unit used in the analyzer, and an analysis method.

The inventors have a first thin film having a first opening, and a second opening connected to the first opening and having a diameter larger than the diameter of the first opening. The above-described problem can be solved by providing a measurement unit including a second thin film having a FET structure including a source electrode, a drain electrode, and a channel around the second opening. I found.
That is, the present invention includes the following inventions.

(1) a first thin film having a first opening;
A second thin film having a second opening connected to the first opening and having a diameter larger than the diameter of the first opening;
A measurement unit for an analyzer, wherein an FET structure including a source electrode, a drain electrode, and a channel is provided around the second opening.

(2) When the cross-sectional shape of the first opening is circular, the diameter is 1.0 nm, the short diameter is elliptical, and the inscribed circle diameter is 1.0 nm to 10 nm when polygonal. The measuring unit according to (1).

(3) The measurement unit according to (1), wherein the thickness of the first thin film is 0.335 to 200 nm.

(4) The value obtained by dividing the height of the first opening by the square of the diameter of the first opening is 2 as the height of the second opening is the diameter of the second opening. The measurement unit according to (1), which is 0.01 to 100 times the value divided by the power.

(5) The measurement unit according to (1), wherein a height of the second opening is not more than 100 times a diameter of the second opening.

(6) The measurement unit according to (1), wherein the material of the first thin film is graphene.

(7) The measuring unit according to (1), wherein the second thin film is provided with a plurality of the FET structures.

(8) a first solution tank;
A second solution tank;
At least one measuring unit disposed between the first solution tank and the second solution tank;
A control unit,
The measurement unit includes a first thin film having a first opening, and a second opening connected to the first opening and having a diameter larger than the diameter of the first opening. An FET structure including a source electrode, a drain electrode, and a channel is provided around the second opening.
The said control part is an analyzer which detects the electrical potential change of the said FET structure vicinity accompanying the partial blockade of the said 1st opening part by a measuring object.

(9) When the cross-sectional shape of the first opening is circular, the diameter is 1.0 nm, the short diameter is elliptical, and the diameter of the inscribed circle is 1.0 nm to 10 nm when polygonal. The analyzer according to (8).

(10) The analyzer according to (8), wherein the thickness of the first thin film is 0.335 to 200 nm.

(11) The value obtained by dividing the height of the first opening by the square of the diameter of the first opening is 2 as the height of the second opening. The analyzer according to (8), which is 0.01 to 100 times the value divided by the power.

(12) The analyzer according to (8), wherein the height of the second opening is not more than 100 times the diameter of the second opening.

(13) The analyzer according to (8), wherein the material of the first thin film is graphene.

(14) The analyzer according to (8), wherein a plurality of the FET structures are provided in the second thin film.

(15) A step of passing a measurement object through at least one measurement unit disposed between the first solution tank and the second solution tank, wherein the measurement unit has a first opening. A first thin film, and a second thin film having a second opening connected to the first opening and having a diameter larger than that of the first opening. An FET structure including a source electrode, a drain electrode, and a channel is provided around the portion, and the measurement object passes through the first opening by an electric field passing through the first opening. To control, step, and
Detecting a potential change in the vicinity of the FET structure due to partial blockage of the first opening by the measurement object.

According to the present invention, it is possible to detect and analyze a polymer with high throughput and high spatial resolution.
Further features related to the present invention will become apparent from the description of the present specification and the accompanying drawings. Further, problems, configurations and effects other than those described above will be clarified by the description of the following examples.

It is a figure which shows 1st Example of this invention, and is a perspective view of an example of the measurement unit used for an analyzer. It is a figure which shows 1st Example of this invention and is a perspective view of another example of the measurement unit used for an analyzer. It is AA sectional view taken on the line of FIG. 1A. FIG. 1B is a top view of FIG. 1A. FIG. 1B is a top view of FIG. 1B. It is an expansion perspective view of the 1st opening part vicinity of a 1st thin film. It is a graph which shows the electric potential change when DNA passes the 1st opening part. It is a graph which shows the relationship between the resistance ratio (1st opening part / 2nd opening part) of an opening part, and the electric potential change when DNA passes the 1st opening part. It is a figure which shows the structure of 2nd Example of this invention. It is a figure which shows the electric system in 2nd Example of this invention. It is a figure which shows the structure of 3rd Example of this invention. It is the sectional view on the AA line of FIG. 6A.

  Embodiments of the present invention will be described below with reference to the accompanying drawings. The accompanying drawings show specific embodiments in accordance with the principle of the present invention, but these are for the understanding of the present invention, and are never used to interpret the present invention in a limited manner. is not. In addition, the same reference number is attached | subjected about the common component in each figure.

The “nanopore” described in each example is a nano-sized hole provided in the thin film and penetrates the front and back of the thin film. A thin film having nanopores is mainly formed from an inorganic material. Examples of the thin film material include SiN, SiO ₂ , graphene, graphite, and Si. In addition, the thin film material may include an organic substance, a polymer material, and the like.

[First embodiment]
FIG. 1A is a perspective view illustrating an example of a measurement unit used in an analyzer, and a shape of a second opening described below is a rectangular parallelepiped. FIG. 1B shows another example of the measurement unit, and is a perspective view when the shape of the second opening is a cylinder. 1C is a cross-sectional view taken along the line AA of FIG. 1A and is a cross-sectional view of a plane parallel to the XY plane and passing through the nanopore. 1D is a top view of FIG. 1A, and FIG. 1E is a top view of FIG. 1B.

  1A, the measurement unit includes a first thin film 100 and a second thin film 104 stacked on the first thin film 100. The first thin film 100 has a first opening 105, and the first opening 105 corresponds to the nanopore described above. The second thin film 104 has a second opening 106. As the material of the second thin film 104, the same material as the material for the first thin film 100 described above may be used, or other materials may be used. The second opening 106 is connected to the first opening 105, and the diameter of the second opening 106 is larger than the diameter of the first opening 105. In the example of FIGS. 1D and 1E, the first opening 105 is disposed at a substantially central position of the second opening 106 in a top view. However, the first opening 105 is not limited to this configuration. The part 105 and the 2nd opening part 106 should just be connected. A plurality of first openings 105 may be provided.

  The second thin film 104 has an FTE structure around the second opening 106. The FTE structure includes a channel 101, a source electrode 102, and a drain electrode 103. The source electrode 102 and the drain electrode 103 are disposed at positions facing each other with the second opening 106 interposed therebetween. The channel 101 is disposed so as to connect the source electrode 102 and the drain electrode 103. The second opening 106 passes through the position of the channel 101. For example, the channel 101 is non-doped silicon, P-type silicon, or low-concentration N-type silicon, and the source electrode 102 and the drain electrode 103 are N-type silicon (Si). Note that a wiring or the like serving as a contact to the source electrode 102 and the drain electrode 103 is provided, but is omitted in FIGS. 1A to 1E.

  FIG. 1F is an enlarged perspective view of the vicinity of the first opening 105 of the first thin film 100. As shown in FIG. 1F, the DNA 107 to be measured passes through the first opening 105 (a series of blocks of the DNA 107 in FIG. 1F represents a series of bases).

  By filling the entire configuration of this embodiment with a conductive solution and applying a potential gradient in the Y-axis direction, a potential gradient is formed in the first opening 105 and the second opening 106. When a potential gradient is applied in the Y-axis positive direction and DNA 107 is added to the conductive solution, DNA 107 has a negative charge, and thus passes through the first opening 105 in the Y-axis negative direction. In this way, the DNA 107 that is the measurement target is controlled to pass through the first opening 105 by the electric field in the direction penetrating the first opening 105. In this configuration, detection and analysis of DNA are performed by detecting a change in potential of the second opening 106 accompanying the passage of DNA through the first opening 105 as a change in the channel current value of the FET.

  When DNA passes through the first opening 105, the movement of ions contained in the solution of the first opening 105 is partially blocked. Therefore, the resistance value of the first opening 105 increases. Since the entire potential difference does not change, the potential difference of the first opening 105 increases and the potential difference of the second opening 106 decreases by blocking the first opening 105. As a result, the potential in the vicinity of the FET installed on the second thin film 104 changes, and the channel current value of the FET changes.

  FIG. 2 is a diagram illustrating an example of potential changes in the first opening and the second opening. FIG. 2 shows a voltage of 1.0 V, a DNA diameter of 1.4 nm, a diameter of the first opening 105 of 2 nm, and a height of the first opening 105 (the length in the direction in which the measurement object passes) is 10 nm. In the example, the diameter of the second opening 106 is 10 nm, and the height of the second opening 106 (the length in the direction in which the measurement target passes) is 100 nm.

  It is considered that the difference between the potential with DNA passing and the potential without DNA passing is proportional to the detection sensitivity of the FET. In the second opening 106, the difference between the potential with DNA passing and the potential without DNA passing becomes large at a position close to the first opening 105 (position where the Y coordinate is small), so that the FET of the second opening 106 If the position where the structure is installed is close to the first opening 105, the detection sensitivity is considered to be high.

  In order to detect DNA with the conventional configuration shown in Non-Patent Document 2, a salt concentration gradient is required in the solution before and after the first opening (nanopore), and the salt concentration on the DNA introduction side is derived. It is necessary to make it higher than the side. Since the potential difference on the DNA introduction side is lower than that on the derivation side, the electric field in the vicinity of the opening end on the introduction side of the first opening is weaker than that on the derivation side, and the frequency of passage through the first opening of DNA is reduced. . On the other hand, in the configuration of this embodiment, the DNA 107 can be detected and analyzed without providing a gradient in the salt concentration of the solution around the first opening 105. Therefore, the electric field in the vicinity of the opening end of the first opening 105 is strong, and the passing frequency of the DNA 107 through the first opening 105 increases. For this reason, the detection frequency of the DNA 107 is increased, and the measurement throughput is improved.

  In the present embodiment, the first opening 105 is formed in the first thin film 100, and the length of the first opening 105 (the length in the direction in which the measurement target passes) is the first thin film. The thickness is 100. Further, the second thin film 104 is provided in the vicinity of the first opening 105, and the first thin film 100 has a stable structure. Therefore, it is easy to produce a thinner first thin film 100. Since the diameter of the first opening 105 is smaller than the diameter of the second opening 106, the spatial resolution is determined by the thickness of the first thin film 100 in which the first opening 105 is installed. Therefore, the spatial resolution can be improved by reducing the thickness of the first thin film 100. In particular, the material of the first thin film 100 may be one layer of graphene, and the thickness of the first thin film 100 may be 0.335 nm which is equal to or less than one base (0.34 nm). Specifically, the thickness of the thin film portion is 0.335 nm to 200 nm, preferably 0.335 nm to 100 nm, and more preferably 0.335 to 0.34 nm.

  An appropriate size can be selected as the diameter of the first opening 105 depending on the type of polymer to be analyzed. The diameter of the single-stranded DNA to be analyzed by the DNA sequencer is about 1.4 nm in an unstretched state, and an appropriate range of the first opening diameter for analyzing the single-stranded DNA is 1.0 nm. About 10 nm, preferably about 1.0 nm to 2.0 nm.

  The diameter of the double-stranded DNA is about 2.6 nm in an unstretched state, and an appropriate range of the diameter of the first opening 105 for analyzing the dsDNA is about 2.0 nm to 10 nm, preferably 2. It is about 0 nm to 4 nm. In addition, the cross-sectional shape of the first opening 105 is not limited to a circle, and may be an ellipse or a polygon. The diameter size described above may be applied to the minor diameter when applied to an ellipse, and may be applied to the diameter of the inscribed circle in the case of a polygon.

  FIG. 3 shows that when the diameter of the first opening 105 is 1.45 to 3 nm, the resistance ratio of the opening (first opening 105 / second opening 106) and DNA are the first opening. FIG. 6 is a diagram showing an example of the relationship of potential change of the second opening 106 when passing through 105. The voltage applied to the entire first opening 105 and second opening 106 was 1 V, and the DNA diameter was 1.4 nm. The resistance ratio was calculated by the ratio of the value obtained by dividing the height of the opening by the square of the diameter. The potential change showed the potential change at the boundary position between the first opening 105 and the second opening 106. The potential change is proportional to the detection sensitivity of DNA passage, and becomes maximum at a resistance ratio of 0.1 to 1. A suitable range of the resistance ratio is 0.01 to 100, preferably 0.1 to 10.

  If an attempt is made to produce an opening having a large ratio of height to diameter in the production of the second opening 106, the second opening 106 may not reach the first thin film 100 due to the manufacturing method. Therefore, the height of the second opening 106 is preferably 100 times or less of the diameter.

  1A and 1B show perspective views in the case where the second opening 106 is a rectangular parallelepiped and a cylinder, but the cross-sectional shape of the second opening 106 in the XZ direction is not limited to a rectangle or a circle. It can also be a polygon or an ellipse. The installation position of the second thin film 104 having the second opening 106 may be on the DNA introduction side or the DNA lead-out side. Whether the second thin film 104 having the second opening 106 is installed on either the DNA introduction side or the DNA extraction side, the polymer contained in the first opening 105 can be detected. The position is not limited to either the DNA introduction side or the extraction side.

  According to this embodiment, it is possible to detect the polymer without applying a salt concentration gradient to the solution before and after the first opening. Compared with a detection method in which the salt concentration gradient is higher on the inlet side than on the polymer outlet side, the measurement throughput can be improved. Further, the spatial resolution can be improved by reducing the thickness of the first thin film. Although analysis of charged polymers is possible, it is particularly suitable for single-stranded DNA detection and DNA sequencing. As described above, it is possible to provide a measurement unit that does not require a salt concentration gradient for the detection of the polymer and can reduce the thickness of the blocking site by the polymer.

[Second Embodiment]
FIG. 4 shows a second embodiment. FIG. 4 is a diagram showing one configuration of a DNA base sequence measurement system using a nanopore FET array substrate (hereinafter referred to as an FET array substrate).

  A measurement unit in which two or more nanopore FETs 110 are arrayed is provided on the FET array substrate 201, and this measurement unit can be used as a disposable consumable. As shown in FIG. 4, the nanopore FET 110 corresponds to the measurement unit described as the first embodiment.

  The DNA base sequence measurement system includes a flow cell 230. The flow cell 230 includes a first solution tank 202, a second solution tank 203, and an FET array substrate 201 disposed between the first solution tank 202 and the second solution tank 203. The first solution tank 202 and the second solution tank 203 are separated by a partition body 250, and the FET array substrate 201 including the nanopore FET 110 is installed in the partition body 250. In this embodiment, the nanopore FET 110 is disposed so as to be in contact with the solution on the second solution tank 203 side. Therefore, as shown in FIG. 4, the nanopore FET 110 is installed in the partition 250 so that the first thin film 100 is on the upper side. The nanopore FET 110 may be disposed so as to be in contact with the solution on the first solution tank 202 side.

  The solution in the DNA sample solution container 206 or the buffer container 207 is injected into the first solution tank 202 by the pump 205 through the injection path 204. Valves 208 and 209 are attached to these containers 206 and 207, respectively, and the solution to be injected can be selected by opening and closing the valves 208 and 209.

  The solution in the first solution tank 202 passes through the discharge path 210 and is stored in the waste liquid container 211. A valve 212 is also attached to the waste liquid container 211, so that backflow of the waste liquid can be prevented. Similarly, the buffer solution is injected into the second solution tank 203 from the buffer container 213 through the injection path 215 by the pump 214. Excess waste liquid is discharged to the waste liquid container 217 through the discharge path 216. Although not shown in the drawing, the pumps 205 and 214 and the valves 208, 209 and 212 are all connected to the control unit 240, and their operations are automatically controlled.

  A negative electrode 219 is immersed in the first solution tank 202, and a positive electrode 218 is immersed in the second solution tank 203. The second solution tank 203 is filled with a buffer solution. In the first solution tank 202, the DNA to be decoded in this embodiment floats in the buffer solution. Since the buffer solution contains an ionic substance, an ionic current is generated between the negative electrode 219 and the positive electrode 218 by applying a voltage between the first solution tank 202 and the second solution tank 203. . Between the negative electrode 219 and the positive electrode 218, a first power source 220 for applying a voltage between both electrodes and an ammeter 221 for measuring an ion current value are installed. The ammeter 221 includes an amplifier and an analog / digital (AD) converter.

  As shown in FIG. 4, the first power supply 220 and the ammeter 221 are each connected to the control unit 240, and the control unit 240 controls the applied voltage and stores the acquired current value. It goes without saying that the control unit 240 can be configured by a computer having a normal central processing unit (CPU), a storage unit such as a memory, an input / output unit such as a keyboard and a display, and a communication interface.

  The ammeter 221 can measure an ion current and a blocking current when DNA passes through the first opening 105. A voltage higher than the negative electrode 219 by about 1 V is applied to the positive electrode 218. As a result, the potential of the second solution tank 203 is higher than that of the first solution tank 202. Since the DNA floating in the first solution tank 202 is negatively charged, it passes through the first opening 105 and moves to the second solution tank 203. A configuration may be adopted in which DNA is injected into the second solution tank 203 instead of the first solution tank 202. In that case, a voltage higher than that of the positive electrode 218 may be applied to the negative electrode 219. Thus, the DNA to be measured is controlled to pass through the first opening 105 by the electric field in the direction penetrating the first opening 105.

  In this configuration, the control unit 240 acquires from the ammeter 221 information on the ionic current and information on the blocking current when the DNA passes through the first opening 105. Then, the control unit 240 detects a change in the potential of the second opening 106 accompanying the DNA passage through the first opening 105 as a change in the channel current value of the FET. Thereby, the control unit 240 detects and analyzes DNA. Note that the detection result of the control unit 240 can be confirmed by an operator using the above-described display or the like.

  FIG. 5 is a circuit diagram showing an electrical system of the FET array substrate 201 of the present embodiment. In FIG. 5, three nanopore FETs 110 a, nanopore FET 110 b, and nanopore FET 110 c are arranged on the FET array substrate 201. The present invention is not limited to this, and it is sufficient that two or more nanopore FETs are arrayed. A number of nanopore FETs are preferably arranged as described above. In FIG. 5, nanopore FETs are arranged one-dimensionally, but they may be arranged two-dimensionally.

  In the nanopore FET 110a, the source electrode 102 is connected to the second power supply 301a. Similarly, in the other nanopore FET 110b and nanopore FET 110c, the source electrodes are connected to the second electrodes 301b and 301c, respectively. Different voltages can be independently applied to the electrodes of the nanopore FET 110a, the nanopore FET 110b, and the nanopore FET 110c.

  In the nanopore FET 110a, the channel current flowing between the source electrode 102 and the drain electrode 103 is converted into a digital signal by an amplifier and an analog-digital converter (AD converter) built in the ammeter 302a and sent to the memory of the control unit 240. It is done. All the power supplies 301a, 301b, 301c and the ammeters 302a, 302b, 302c are connected to the control unit 240 via the connector 310, and the voltage of each power supply is automatically controlled by the control unit 240.

  According to this embodiment, it is possible to detect the polymer without applying a salt concentration gradient to the solution before and after the first opening. By arranging the nanopore FET structure shown in the first embodiment in an array, it is possible to provide a DNA base sequence measurement system with further improved measurement throughput.

[Third embodiment]
6A and 6B show a third embodiment. 6A is a perspective view, and FIG. 6B is a cross-sectional view taken along line AA in FIG. 6A (a cross-sectional view taken along a plane parallel to the XY plane and passing through the first opening 105 in FIG. 6A). In the third embodiment, a plurality of FET structures shown in the first embodiment are provided. The FET structure shown in FIGS. 6A and 6B includes a channel 101, a source electrode 102, and a drain electrode 103, as described above.

  According to this example, two kinds of potential changes derived from the blockade of DNA in the same region can be detected as DNA passes through the first opening 105, so that the accuracy of analysis can be improved.

  In addition, this invention is not limited to the Example mentioned above, Various modifications are included. For example, the above-described embodiments have been described in detail for easy understanding of the present invention, and are not necessarily limited to those having all the configurations described. In addition, a part of the configuration of one embodiment may be replaced with the configuration of another embodiment, and the configuration of another embodiment may be added to the configuration of one embodiment. Further, it is possible to add, delete, and replace other configurations for a part of the configuration of each embodiment.

  The processing, functions, and the like of the control unit 240 may be realized by hardware by designing a part or all of them, for example, with an integrated circuit. The processing, functions, and the like of the control unit 240 may be realized by software by the processor interpreting and executing a program that realizes each function. Information such as programs, tables, and files that realize each function can be stored in a storage device such as a memory, a hard disk, or an SSD (Solid State Drive), or a storage medium such as an IC card, an SD card, or a DVD.

  In the above-described embodiments, control lines and information lines are those that are considered necessary for the explanation, and not all control lines and information lines on the product are necessarily shown. Actually, it may be considered that almost all the components are connected to each other.

100 first thin film 101 channel 102 source electrode 103 drain electrode 104 second thin film 105 first opening 106 second opening 107 DNA
110, 110a, 110b, 110c Nanopore FET
201 FET array substrate 202 First solution tank 203 Second solution tank 204, 215 Injection path 205, 214 Pump 206 DNA sample solution container 207, 213 Buffer container 208, 209, 212 Valve 210, 216 Discharge path 211, 217 Waste liquid Container 218 Positive electrode 219 Negative electrode 220 Power supply 221 Ammeter 230 Flow cell 240 Control unit 250 Partitions 301a, 301b, 301c Power supplies 302a, 302b, 302c Ammeter 310 Connector

Claims (15)

A first thin film having a first opening;
A second thin film having a second opening connected to the first opening and having a diameter larger than the diameter of the first opening;
A measurement unit for an analyzer, wherein an FET structure including a source electrode, a drain electrode, and a channel is provided around the second opening. The measuring unit according to claim 1,
The diameter of the first opening is circular when the cross-sectional shape is circular, the short diameter is elliptical, and the diameter of the inscribed circle is 1.0 nm to 10 nm when polygonal. Characteristic measuring unit. The measuring unit according to claim 1,
The thickness of said 1st thin film is 0.335-200 nm, The measuring unit characterized by the above-mentioned. The measuring unit according to claim 1,
The value obtained by dividing the height of the first opening by the square of the diameter of the first opening is obtained by dividing the height of the second opening by the square of the diameter of the second opening. A measurement unit characterized by being 0.01 to 100 times the measured value. The measuring unit according to claim 1,
The measurement unit, wherein the height of the second opening is not more than 100 times the diameter of the second opening. The measuring unit according to claim 1,
The measurement unit, wherein the material of the first thin film is graphene. The measuring unit according to claim 1,
A measuring unit comprising a plurality of the FET structures provided on the second thin film. A first solution tank;
A second solution tank;
At least one measuring unit disposed between the first solution tank and the second solution tank;
A control unit,
The measurement unit includes a first thin film having a first opening, and a second opening connected to the first opening and having a diameter larger than the diameter of the first opening. An FET structure including a source electrode, a drain electrode, and a channel is provided around the second opening.
The control unit detects an electrical potential change in the vicinity of the FET structure due to partial blockage of the first opening by a measurement target. The analyzer according to claim 8, wherein
The diameter of the first opening is circular when the cross-sectional shape is circular, the short diameter is elliptical, and the diameter of the inscribed circle is 1.0 nm to 10 nm when polygonal. Characteristic analyzer. The analyzer according to claim 8, wherein
An analyzer characterized in that the thickness of the first thin film is 0.335 to 200 nm. The analyzer according to claim 8, wherein
The value obtained by dividing the height of the first opening by the square of the diameter of the first opening is obtained by dividing the height of the second opening by the square of the diameter of the second opening. The analyzer is 0.01 to 100 times the measured value. The analyzer according to claim 8, wherein
The analyzer according to claim 1, wherein the height of the second opening is not more than 100 times the diameter of the second opening. The analyzer according to claim 8, wherein
An analysis apparatus, wherein the material of the first thin film is graphene. The analyzer according to claim 8, wherein
An analysis apparatus comprising a plurality of the FET structures provided on the second thin film. A step of passing a measurement object through at least one measurement unit disposed between the first solution tank and the second solution tank, wherein the measurement unit includes a first thin film having a first opening; And a second thin film coupled to the first opening and having a second opening having a diameter larger than the diameter of the first opening, and surrounding the second opening Is provided with a FET structure including a source electrode, a drain electrode, and a channel, and is controlled so that the measurement object passes through the first opening by an electric field passing through the first opening. Step,
Detecting a potential change in the vicinity of the FET structure due to partial blockage of the first opening by the measurement object.

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