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EP-4455656-B1 - CHANNEL DEVICE

EP4455656B1EP 4455656 B1EP4455656 B1EP 4455656B1EP-4455656-B1

Inventors

  • NAKATANI, NORIYUKI

Dates

Publication Date
20260513
Application Date
20221116

Claims (14)

  1. A channel device (1, 1a) for application to measurement of electrical resistance of cellular tissue (9), comprising: an intermediate member (10) including a measurement chamber (100) formed by a through hole passing therethrough in a first direction; a first lid member (21) positioned on a surface of said intermediate member (10) which is on a first side as seen in said first direction and closing an opening at a first edge of said measurement chamber (100) as seen in said first direction; a second lid member (22) positioned on a surface of said intermediate member (10) which is on a second side as seen in said first direction and closing an opening at a second edge of said measurement chamber (100) as seen in said first direction; a porous membrane (30) positioned in said measurement chamber (100) and partitioning said measurement chamber (100) into a first chamber (101) on the first side and a second chamber (102) on the second side as seen in said first direction, said porous membrane (30) being permeable to liquid; a first-side working electrode (61) and a first-side reference electrode (71) both positioned on a surface of said first lid member (21) which is on the second side as seen in said first direction and overlapping said measurement chamber (100) as seen in said first direction; and a second-side working electrode (63) and a second-side reference electrode (73) both positioned on a surface of said second lid member (22) which is on the first side as seen in said first direction and overlapping said measurement chamber (100) as seen in said first direction, wherein said first-side working electrode (61) includes a first first-side working portion (611), and a second first-side working portion (612) spaced toward a first side in a second direction intersecting said first direction apart from said first first-side working portion (611), characterized in that a dimension from an edge of said first first-side working portion (611) which is on a second side as seen in said second direction to an edge of said second first-side working portion (612) which is on the first side as seen in said second direction is greater than the width of said measurement chamber (100) as measured in said second direction, and wherein a distance between said first first-side working portion (611) and said second first-side working portion (612) as measured in said second direction is smaller than the width of said measurement chamber (100).
  2. The channel device (1, 1a) according to Claim 1, wherein said first-side reference electrode (71) includes a first first-side reference portion (711), and a second first-side reference portion (712) spaced toward the first side in said second direction apart from said first first-side reference portion (711), and wherein said first first-side reference portion (711) and said second first-side reference portion (712) are positioned between said first first-side working portion (611) and said second first-side working portion (612) as seen in said second direction.
  3. The channel device (1, 1a) according to Claim 2, wherein said first-side working electrode (61) further includes a third first-side working portion (613) positioned between said first first-side reference portion (711) and said second first-side reference portion (712) as seen in said second direction.
  4. The channel device (1, 1a) according to Claim 3, wherein the width of said first first-side working portion (611) as measured in said second direction is greater than the width of said third first-side working portion (613) as measured in said second direction.
  5. The channel device (1, 1a) according to Claim 3 or 4, wherein said first-side working electrode (61) further includes a fourth first-side working portion (614) positioned between said first first-side reference portion (711) and said second first-side reference portion (712) as seen in said second direction and spaced toward the first side in said second direction apart from said third first-side working portion (613).
  6. The channel device (1, 1a) according to Claim 5, wherein said second-side working electrode (63) includes a first second-side working portion (631), and a second second-side working portion (632) spaced toward the first side in said second direction apart from said first second-side working portion (631), wherein said first second-side working portion (631) is in opposed relation to said first first-side working portion (611) as seen in said first direction, wherein said second second-side working portion (632) is in opposed relation to said second first-side working portion (612) as seen in said first direction, wherein a dimension from an edge of said first second-side working portion (631) which is on the second side as seen in said second direction to an edge of said second second-side working portion (632) which is on the first side as seen in said second direction is greater than the width of said measurement chamber (100) as measured in said second direction, and wherein a distance between said first second-side working portion (631) and said second second-side working portion (632) as measured in said second direction is smaller than the width of said measurement chamber (100) as measured in said second direction.
  7. The channel device (1, 1a) according to Claim 6, wherein said second-side reference electrode (73) includes a first second-side reference portion (731), and a second second-side reference portion (732) spaced toward the first side in said second direction apart from said first second-side reference portion (731), and wherein said first second-side reference portion (731) and said second second-side reference portion (732) are positioned between said first second-side working portion (631) and said second second-side working portion (632) as seen in said second direction.
  8. The channel device (1, 1a) according to Claim 7, wherein said second-side working electrode (63) further includes a third second-side working portion (633) positioned between said first second-side reference portion (731) and said second second-side reference portion (732) as seen in said second direction.
  9. The channel device (1, 1a) according to Claim 8, wherein said second-side working electrode (63) further includes a fourth second-side working portion (634) positioned between said first second-side reference portion (731) and said second second-side reference portion (732) as seen in said second direction and spaced toward the first side in said second direction apart from said third second-side working portion (633).
  10. The channel device (1, 1a) according to any one of Claims 1 to 9, wherein said intermediate member (10) includes a first intermediate member (11), and a second intermediate member (12) positioned on the first side of said first intermediate member (11) as seen in said first direction, wherein said first intermediate member (11) includes said first chamber (101), wherein said second intermediate member (12) includes said second chamber (102), and wherein said porous membrane (30) is positioned between said first intermediate member (11) and said second intermediate member (12) as seen in said first direction.
  11. The channel device (1, 1a) according to any one of Claims 1 to 10, wherein said intermediate member (10) includes a first channel (51) in communication with said first chamber (101), and a second channel (53) in communication with said second chamber (102).
  12. The channel device (1, 1a) according to Claim 11, wherein said first lid member (21) includes a first through hole (43) in communication with said first channel (51), and a second through hole (45) in communication with said second channel (53).
  13. The channel device (1, 1a) according to any one of Claims 1 to 12, wherein said measurement chamber (100), said first first-side working portion (611), and said second first-side working portion (612) extend in a third direction intersecting said first and second directions.
  14. The channel device (1, 1a) according to Claim 13, wherein said first first-side working portion (611) and said second first-side working portion (612) extend from a position spaced toward a first side in said third direction apart from said measurement chamber (100) to a position spaced toward a second side in said third direction apart from said measurement chamber (100).

Description

Technical Field The present invention relates to a channel device for application to measurement of electrical resistance of cellular tissue. Background Art Transepithelial electrical resistance (TEER) measurement has been known as a method of evaluating the barrier function of cell layers that form a membrane structure. In the TEER measurement, an insert having a tubular shape with a bottom formed by a porous membrane is placed in a recessed portion of a culture plate, and cells are cultured on the porous membrane. Working electrodes for applying current and reference electrodes for measuring a potential difference are placed inside and outside the insert. The potential difference generated between the reference electrodes is measured while the current is applied between the working electrodes, whereby electrical resistance of the cell layers is calculated. For example, Patent Literature 1 discloses that the electrical resistance is measured by inserting electrodes (10A and 10B) from one side inside and outside a culture insertion dish (21). For the insertion of the electrodes from one side, it is however necessary to open the top of the culture insertion dish (21). This technique is not applicable to a device which does not have such an opening at the top. JP2020146015A also discloses a channel device for application to measurement of electrical resistance of cellular tissue. On the other hand, Non Patent Literature 1 discloses a channel device in which electrodes are placed on a lid which closes a top opening of a culture vessel. Placing the electrodes on the lid in this manner allows the measurement of the electrical resistance of cell layers being cultured in a measurement chamber. Citation List Patent Literature Patent Literature 1: Japanese Patent Application Laid-Open No. 2005-137307 Non Patent Literature Non Patent Literature 1: Booth R, Kim H. Characterization of a microfluidic in vitro model of the blood-brain barrier (mu BBB) Lab Chip. 2012 Apr. 24;12(10):1784-92. Summary of Invention Technical Problem During the assembly of the channel device as disclosed in Non Patent Literature 1, the electrodes are misaligned relative to the measurement chamber if the lid is mounted in a position misaligned relative to the measurement chamber. Also, when the electrodes are positioned near an edge of the measurement chamber, there have been cases in which the misalignment of the lid fluctuates the area (contact area) of the electrodes in contact with a liquid in the measurement chamber. Thus, the misalignment of the electrodes or the fluctuations in contact area causes fluctuations in current density distribution in the measurement chamber. This results in a danger that measurement results of the electrical resistance fluctuate. It is an object of the present invention to provide a technique capable of reducing variations in measurement results of electrical resistance due to the assembly accuracy of a channel device. Solution to Problem To solve the aforementioned problem, a first aspect is intended for a channel device for application to measurement of electrical resistance of cellular tissue, comprising: an intermediate member including a measurement chamber formed by a through hole passing therethrough in a first direction; a first lid member positioned on a surface of the intermediate member which is on a first side as seen in the first direction and closing an opening at a first edge of the measurement chamber as seen in the first direction; a second lid member positioned on a surface of the intermediate member which is on a second side as seen in the first direction and closing an opening at a second edge of the measurement chamber as seen in the first direction; a porous membrane positioned in the measurement chamber and partitioning the measurement chamber into a first chamber on the first side and a second chamber on the second side as seen in the first direction, the porous membrane being permeable to liquid; a first-side working electrode and a first-side reference electrode both positioned on a surface of the first lid member which is on the second side as seen in the first direction and overlapping the measurement chamber as seen in the first direction; and a second-side working electrode and a second-side reference electrode both positioned on a surface of the second lid member which is on the first side as seen in the first direction and overlapping the measurement chamber as seen in the first direction, wherein the first-side working electrode includes a first first-side working portion, and a second first-side working portion spaced toward a first side in a second direction intersecting the first direction apart from the first first-side working portion, wherein a dimension from an edge of the first first-side working portion which is on a second side as seen in the second direction to an edge of the second first-side working portion which is on the first side as seen in the second direction