Pore chip shell and microparticle measuring system

Abstract

The aperture chip housing (700) accommodates the aperture chip (110). The main body (710) comprises a chip accommodating space (720), a first space (722) and a second space (724). The aperture chip (110) is housed in the chip housing space (720) and is supported on the vertical surface. The first space (722) and the second space (724) are adjacent to each other in the horizontal direction and are divided by the aperture chip (110).

Description

Technical Field

[0001] This disclosure relates to measurement using a pore device. Background Art

[0002] A particle size distribution measurement method called the resistance method (Coulter principle) is known. In this measurement method, an electrolyte solution containing particles is passed through a fine pore called a nanopore. When a particle passes through the fine pore, the amount of electrolyte solution in the fine pore decreases by an amount corresponding to the volume of the particle, increasing the resistance of the fine pore. Therefore, by measuring the resistance of the fine pore, the volume (i.e., particle size) of the particle can be measured.

[0003] Figure 1 is a block diagram of a microparticle measurement system 1R using the resistance method. The microparticle measurement system 1R includes a pore device 100, a measurement device 200R, and a data processing device 300.

[0004] The inside of the pore device 100 is filled with an electrolyte solution 2 containing particles 4 to be detected. The inside of the pore device 100 is divided into two spaces by a pore chip 102, and electrodes 106 and 108 are provided in the two spaces. If a potential difference is generated between electrode 106 and electrode 108, an ionic current flows between the electrodes, and particles 4 move from one space to the other through the fine pore 104 by electrophoresis.

[0005] The measurement device 200R generates a potential difference between electrode pair 106, 108 and obtains information related to the resistance value Rp between the electrode pair. The measurement device 200R includes a transimpedance amplifier 210, a voltage source 220, and a digitizer 230. The voltage source 220 generates a potential difference Vb between electrode pair 106, 108. This potential difference Vb serves as a driving source for electrophoresis and as a bias signal for measuring the resistance value Rp.

[0006] A minute current Is that is inversely proportional to the resistance of the fine pore 104 flows between electrode pair 106, 108.

[0007] Is = Vb / Rp...(1)

[0008] The transimpedance amplifier 210 converts the minute current Is into a voltage signal Vs. If the conversion gain is set to r, the following equation holds.

[0009] Vs = -r × Is...(2)

[0010] If Equation (1) is substituted into Equation (2), Equation (3) is obtained.

[0011] Vs = -Vb × r / Rp...(3)

[0012] The digitizer 230 converts the voltage signal Vs into digital data Ds. In this way, the voltage signal Vs inversely proportional to the resistance value Rp of the micropore 104 can be obtained by the measuring device 200R.

[0013] Figure 2 It is a waveform diagram of an exemplary minute current Is measured by the measuring device 200R. It should be noted that, in this specification, the vertical and horizontal axes of the waveform diagrams and time charts are appropriately enlarged or reduced for easy understanding, and each waveform shown is also simplified, exaggerated, or highlighted for easy understanding.

[0014] During the short period when the particle passes through, the resistance value Rp of the micropore 104 increases. Therefore, each time a particle passes through, the current Is decreases in a pulsed manner. The amplitude of each pulsed current is related to the particle size. The data processing device 300 processes the digital data Ds and analyzes the number, particle size distribution, etc. of the particles 4 contained in the electrolyte 2.

[0015] Prior Art Documents

[0016] Patent Documents

[0017] Patent Document 1: Japanese Unexamined Patent Application Publication No. 2017-016881

[0018] Patent Document 2: Japanese Unexamined Patent Application Publication No. 2014-219235

[0019] Patent Document 3: Japanese Unexamined Patent Application Publication No. 2018-054594

[0020] Patent Document 4: International Publication No. 2002 / 084306 Summary of the Invention

[0021] Outline of the Invention

[0022] Problems to be Solved by the Invention

[0023] Figure 3 It is a cross-sectional view of a pore device studied by the inventors. The pore device 100R includes a pore chip 110 and a pore chip housing 800R. The pore chip 110 has pores 112.

[0024] The pore chip housing 800R supports the pore chip 110 on a horizontal plane. The pore chip housing 800R has a first space 802 and a second space 804 divided by the pore chip 110 inside it. The first space 802 communicates with the outside via a flow path 806, and the second space 804 communicates with the outside via a flow path 808.

[0025] Before measurement, a solution is injected into the first space 802 via the flow path 806, and a solution is injected into the second space 804 via the flow path 808.

[0026] As Figure 3 shown, in the package in which the pore chip 110 is disposed horizontally, the pore opening axis faces the vertical direction. Therefore, if a solution is introduced into the spaces 802 and 804, the pores 112 are clamped by the liquid from above and below, and thus an air accumulation 8 is likely to be formed in the pores 112.

[0027] If an air accumulation 8 is generated in the pores 112, the solution cannot enter the pores 112, and thus the current flowing through the pores 112 no longer flows. Moreover, the particles cannot pass through the pores. Further, it is not easy to remove the already generated air accumulation 8. Although there is a method of removing the air accumulation using ultrasonic cleaning or the like, it cannot be said to be highly reliable, and moreover, the membrane having pores formed due to ultrasonic vibration may be damaged.

[0028] As a method for suppressing the generation of air accumulation, a countermeasure of subjecting the pore chip to plasma treatment or the like to make it hydrophilic can be considered, but not only does the treatment take time, but it also becomes a main cause of cost increase.

[0029] The present disclosure has been made in view of such a situation, and one exemplary object of one aspect thereof is to provide a pore chip housing that suppresses the generation of air accumulation.

[0030] Solution to the problem

[0031] One aspect of the pore chip housing of the present disclosure relates to a pore chip housing that houses a pore chip. The main body of the pore chip housing supports the pore chip on a vertical plane. The main body has a first space and a second space that are adjacent to each other in the horizontal direction and are partitioned by the pore chip.

[0032] It should be noted that a mode in which the above-described constituent elements are arbitrarily combined and a mode in which the constituent elements and expressions are mutually replaced between methods, devices, etc. are also effective as aspects of the present invention.

[0033] Advantageous effects of the invention

[0034] According to one aspect of the present disclosure, the generation of air accumulation can be suppressed. Description of the drawings

[0035] Figure 1 is a block diagram of a microparticle measurement system using the resistance method.

[0036] Figure 2 is a waveform diagram of an exemplary minute current Is measured by a measuring device.

[0037] Figure 3 is a cross-sectional view of a pore device studied by the inventors.

[0038] Figure 4 It is a perspective view of the pore chip housing of the embodiment.

[0039] Figure 5 It is a cross-sectional view of the pore chip housing.

[0040] Figure 6 It is a cross-sectional view showing the case where the pore chip housing houses the pore chip.

[0041] Figure 7 It is a cross-sectional view of the periphery of the pore chip of the pore chip housing.

[0042] Figure 8 It is a graph showing the relationship between the water pressure p and the number of passing particles. Detailed Embodiments

[0043] (Summary of the Embodiment)

[0044] The summary of several exemplary embodiments of the present disclosure is described. This summary is a prelude to the detailed description below and is for the purpose of a basic understanding of the embodiment. It simplifies the description of several concepts of one or more embodiments and does not limit the scope of the invention or disclosure. This summary is not an inclusive summary of all the embodiments to be considered, nor does it delimit the scope of a part or all of the forms by identifying important elements of all the embodiments. For simplicity, "one embodiment" is sometimes used to indicate one embodiment (example, variant) or multiple embodiments (examples, variants) disclosed in this specification.

[0045] The pore chip housing of one embodiment houses the pore chip. The pore chip housing includes a main body that supports the pore chip on a vertical plane. The main body has a first space and a second space inside that are adjacent to each other in the horizontal direction and are divided by the pore chip.

[0046] According to this structure, if the solution is filled into the first space and the second space, the liquid level rises from bottom to top. Therefore, it is possible to suppress the accumulation of air in the pores.

[0047] In one embodiment, when the pore chip housing is filled with liquid, the height of the liquid level can be 10 mm or more higher than the height of the pores.

[0048] According to this structure, the water pressure at the pores can be increased compared with the prior art, so that the particle permeability can be improved and the measurement efficiency can be improved.

[0049] In one embodiment, the main body may include: a first flow path that communicates with the upper surface of the main body at a position lower than the position of the pores of the pore chip in the first space; a second flow path that communicates with the upper surface of the main body at a position higher than the position of the pores of the first space; a third flow path that communicates with the upper surface of the main body at a position lower than the position of the pores of the second space; and a fourth flow path that communicates with the upper surface of the main body at a position higher than the position of the pores of the second space.

[0050] In one embodiment, the height of the upper surface of the main body may be 10 mm or more higher than the height of the pores of the pore chip.

[0051] In one embodiment, the main body may further have a convex portion formed on the upper surface of the main body and separating the first flow path and the second flow path from the third flow path and the fourth flow path. Thereby, it is possible to prevent the solution on the first space side from short-circuiting with the solution on the second space side.

[0052] In one embodiment, the pore housing may further include a first electrode provided on the wall surface of the first flow path and a second electrode provided on the wall surface of the third flow path.

[0053] In one embodiment, the pore housing may further include an electrode plate connected to the bottom surface of the main body. The first electrode and the second electrode may be formed on the electrode plate.

[0054] In one embodiment, the main body may be capable of being divided into a first part and a second part with a vertical plane as the boundary.

[0055] In one embodiment, it may further include: a pore device including a pore chip and a pore chip housing for housing the pore chip; and a measuring device having an interface socket for assembling the pore device.

[0056] (Embodiment)

[0057] Hereinafter, with reference to the drawings, preferred embodiments will be described. The same or equivalent components, members, and processes shown in the respective drawings are denoted by the same reference numerals, and repeated descriptions are appropriately omitted. Moreover, the embodiments are illustrative and not restrictive of the invention, and all the features and combinations thereof described in the embodiments are not necessarily the essential features and combinations of the invention.

[0058] In this specification, the "state in which member A is connected to member B" includes not only the case where member A is physically directly connected to member B, but also the case where member A and member B are indirectly connected via other members that do not substantially affect their electrical connection state or do not impair the functions and effects exerted by their combination.

[0059] Similarly, the state where "component C is disposed between component A and component B" includes not only the cases where component A is directly connected to component C or component B is directly connected to component C, but also the cases where they are indirectly connected via other components that do not substantially affect their electrical connection state or impair the functions and effects achieved through their combination.

[0060] In addition, the dimensions (thickness, length, width, etc.) of the components shown in the drawings are sometimes appropriately enlarged or reduced for ease of understanding. Moreover, the dimensions of multiple components do not necessarily represent their size relationships. In the drawings, even if a certain component A is depicted as thicker than another component B, component A may actually be thinner than component B.

[0061] Figure 4 It is a perspective view of the porous chip housing 700 of the embodiment. The porous chip housing 700 includes a main body 710 and an electrode sheet 760. The main body 710 houses and supports a porous chip in its internal chip accommodation space 720.

[0062] Figure 5 It is a cross-sectional view of the porous chip housing 700. The main body 710 includes a first space 722, a chip accommodation space 720, and a second space 724 that are adjacent to each other in the horizontal direction. In a state where a porous chip is housed in the chip accommodation space 720, the first space 722 and the second space 724 are divided by the porous chip.

[0063] A first flow path 741 and a second flow path 742 that communicate from the first space 722 toward the upper surface S1 of the main body 710 are formed inside the main body 710. Specifically, the first flow path 741 communicates from a position lower than the position 721 of the pores of the porous chip in the first space 722 to the first opening 431 on the upper surface S1. The second flow path 742 communicates from a position higher than the position 721 of the pores in the first space 722 to the second opening 732 on the upper surface S1. The first flow path 741 and the third flow path 743 are each L-shaped, having a portion 741a, 743a that extends in the horizontal direction and a portion 741b, 743b that extends in the vertical direction.

[0064] Similarly, a third flow path 743 and a fourth flow path 744 that communicate from the second space 724 toward the upper surface S1 of the main body 710 are formed inside the main body 710. Specifically, the third flow path 743 communicates from a position lower than the position 721 of the pores of the porous chip in the second space 724 to the third opening 433 on the upper surface S1. The fourth flow path 744 communicates from a position higher than the position 721 of the pores in the second space 724 to the fourth opening 734 on the upper surface S1. The second flow path 742 and the fourth flow path 744 are also L-shaped.

[0065] The main body 710 includes a first electrode E1 and a second electrode E2. The first electrode E1 is disposed in the first space 722 or the first flow path 741. Moreover, the second electrode E2 is disposed in the second space 724 or the second flow path 742. The first electrode E1 and the second electrode E2 correspond to Figure 1 the electrodes 106 and 108.

[0066] Return Figure 4 . The electrode sheet 760 is mounted on the bottom surface of the main body 710. The electrode sheet 760 also serves as the inner wall of a part 741a that extends horizontally of the first flow path 741 and a part 743a that extends horizontally of the third flow path 743. The electrode sheet 760 has a first electrode E1 formed in a part corresponding to the inner wall of the first flow path 741 and a second electrode E2 formed in a part corresponding to the inner wall of the third flow path 743.

[0067] The electrode sheet 760 has a contact electrode Ec1 electrically connected to the first electrode E1 and a contact electrode Ec2 electrically connected to the second electrode E2. During measurement, a voltage signal is applied to the contact electrodes Ec1 and Ec2.

[0068] The main body 710 can be divided into a first part 712 and a second part 714. A chip accommodation space 720 is formed on the side of the first part 712.

[0069] On the upper surface S1 of the main body 710, a convex portion 750 is formed at the boundary between the first part 712 and the second part 714, and the first flow path 741 and the second flow path 742 are separated from the third flow path 743 and the fourth flow path 744 by the convex portion 750. The convex portion 750 can prevent a short circuit between the solution on the first space 722 side and the solution on the second space 424 side.

[0070] In a state where the pore chip housing is filled with liquid, the height of the liquid surface is preferably 10 mm or more higher than the position 721 of the pores. The height of the liquid surface can be considered as the height of the upper surface S1.

[0071] Figure 6 is a cross-sectional view showing a case where the pore chip housing 700 accommodates the pore chip 110. The pore chip 110 has pores 112. The pore chip 110 is vertically erected and accommodated in the chip accommodation space 720 of the pore chip housing 700.

[0072] The above is the structure of the pore chip housing 700. Next, its advantages will be described.

[0073] Figure 7It is a cross-sectional view of the periphery of the pore chip 110 of the pore chip housing 700. In the preparation stage of the measurement, the electrolyte 2 is injected from the first opening 731. The electrolyte 2a enters the first space 722 via the first flow path 741. Similarly, the electrolyte 2b is injected from the third opening 733. The electrolyte 2b enters the second space 724 via the third flow path 743. In the first space 722 and the second space 724, the liquid levels 6 of the electrolytes 2a and 2b rise from bottom to top. There is air 7 in the pores 112 of the pore chip 110, but as the liquid level 6 rises, the air 7 can escape upward. Thus, the generation of air accumulation can be suppressed.

[0074] In addition, the pore chip housing 700 also has the following advantages. In this pore chip housing 700, the height difference between the pores 112 and the upper surface S1 is 10 mm or more. This indicates that the water pressure inside the pores 112 increases. The water pressure p is determined by the height h from the pores to the water surface and can be expressed by the following formula.

[0075] p = ρ·gh

[0076] ρ is the density of water and g is the acceleration due to gravity.

[0077] In the microparticle detection system, electrolytes used are mostly chloride-based solutions of less than 1 mol (such as NaCl, KCl, PBS, etc.). Therefore, even if the density hardly changes compared to water, it will not have a great impact.

[0078] ρ = 997 kg / m 3

[0079] g = 9.81 m / s 2

[0080] When ρ = 997 kg / m³ and g = 9.81 m / s², the water pressure p becomes 9781×h [kPa]. If h = 10 mm = 0.01 m, then p = 0.09781 kPa.

[0081] Figure 8 It is a graph showing the relationship between the water pressure p and the number of particles passing through. The horizontal axis represents time and the vertical axis represents the number of particles passing through. It can be seen that when the water pressure p increases, the number of particles passing through per unit time (1 minute) increases. When h = 10 mm and p ≈ 0.1 kPa, more than 6.6 particles can be detected per minute. In order to achieve sufficient measurement accuracy, the total number of particles needs to be about 200. In this embodiment, the measurement can be completed in 30 minutes.

[0082] In the conventional pore chip, the number of particles passing through per unit time is about 3 particles / minute. This indicates that the measurement takes 1 hour. If the pore chip housing 700 of the embodiment is used, the measurement time can be reduced to about half.

[0083] The above describes the embodiments. These embodiments are illustrative, and various variations exist in the combination of these respective constituent elements and processing steps. It is self-evident to those skilled in the art that such variations also fall within the scope of the present invention. Hereinafter, such variations will be described.

[0084] In the embodiment, electrodes E1 and E2 are formed on the electrode sheet 760, but the positions and shapes of electrodes E1 and E2 are not limited. For example, electrode E1 may be formed in the first space 722 or in the second flow path 742. Similarly, electrode E2 may be formed in the second space 724 or in the fourth flow path 744.

[0085] In addition, electrodes E1 and E2 may be rod-shaped detection electrodes. In this case, electrode E1 may be inserted from the first opening 731 or the second opening 732, or at least a part of the detection electrode may be inserted from another opening provided on the side surface of the first part 712 so as to be exposed to any one of the first flow path 741, the first space 722, and the second flow path 742. The same applies to electrode E2.

[0086] Although a microparticle measurement device has been described in this specification, the use of the present invention is not limited thereto, and it can be widely used in measuring devices accompanied by microcurrent measurement using pore devices such as DNA sequencers.

[0087] Although the present invention has been described based on the embodiments, the embodiments merely illustrate the principles and applications of the present invention. In the embodiments, within the scope not departing from the idea of the present invention defined in the claims, many variations and configuration changes are admissible.

[0088] Industrial Applicability

[0089] The present invention relates to measurement using a pore device.

[0090] Reference Signs

[0091] 1 Microparticle Measurement System

[0092] 2 Electrolyte

[0093] 4 Particle

[0094] 8 Air Accumulation

[0095] 100 Pore Device

[0096] 200R Measurement Device

[0097] 210 Transimpedance Amplifier

[0098] 220 Voltage Source

[0099] 230 Digitalizer

[0100] 300 Data processing device

[0101] 100 Pore device

[0102] 110 Pore chip

[0103] 112 Pore

[0104] 700 Pore chip housing

[0105] 710 Main body

[0106] 712 First part

[0107] 714 Second part

[0108] 720 Chip accommodation space

[0109] 722 First space

[0110] 724 Second space

[0111] S1 Upper surface

[0112] 731 First opening

[0113] 732 Second opening

[0114] 733 Third opening

[0115] 734 Fourth opening

[0116] 741 First flow path

[0117] 742 Second flow path

[0118] 743 Third flow path

[0119] 744 Fourth flow path

[0120] 750 Convex part

[0121] 760 Electrode sheet

[0122] E1 First electrode

[0123] E2 Second electrode

Claims

1. A pore chip housing that houses a pore chip, characterized in that, The pore chip housing includes a main body that supports the pore chip in a vertical plane, and the main body has a first space and a second space that are adjacent in the horizontal direction and are divided by the pore chip.

2. The pore chip housing according to claim 1, characterized in that, When the inside of the pore chip housing is filled with a liquid, the height of the liquid level is 10 mm or more higher than the height of the pores of the pore chip.

3. The pore chip housing according to claim 1, characterized in that, The main body includes: A first flow path that communicates with the upper surface of the main body starting from a position lower than the position of the pores of the pore chip in the first space; A second flow path that communicates with the upper surface of the main body starting from a position higher than the position of the pores in the first space; A third flow path that communicates with the upper surface of the main body starting from a position lower than the position of the pores of the pore chip in the second space; And A fourth flow path that communicates with the upper surface of the main body starting from a position higher than the position of the pores in the second space.

4. The pore chip housing according to claim 3, characterized in that, The height of the upper surface of the main body is 10 mm or more higher than the height of the pores of the pore chip.

5. The pore chip housing according to claim 3 or 4, characterized in that, The main body further has a convex portion on the upper surface of the main body, and the convex portion separates the first flow path and the second flow path from the third flow path and the fourth flow path.

6. The pore chip housing according to claim 3 or 4, characterized in that, The pore chip housing further includes: A first electrode provided on the wall surface of the first flow path; and A second electrode provided on the wall surface of the third flow path.

7. The pore chip housing according to claim 6, characterized in that, The pore chip housing further has an electrode plate connected to the bottom surface of the main body, and the first electrode and the second electrode are formed on the electrode plate.

8. The pore chip housing according to claim 1 or 2, characterized in that, The main body can be divided into a first part and a second part with the vertical plane as the boundary.

9. A microparticle measurement system, characterized in that, It includes: A pore device that includes the pore chip and the pore chip housing according to claim 1 or 2 that houses the pore chip; and A measuring device that has an interface socket for assembling the pore device.

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