EP-4741485-A1 - MICROFLUIDIC CHIP

EP4741485A1EP 4741485 A1EP4741485 A1EP 4741485A1EP-4741485-A1

Abstract

Provided is a microfluidic chip having enhanced visibility and connection of an interface structure. The microfluidic chip includes a first substrate and a second substrate. The first substrate includes: a first groove part extending in a first direction; a second groove part, a portion of which extends in the first direction; a third groove part, a portion of which extends in the first direction; a first protrusion part; and a second protrusion part. The first groove part and the second groove part are adjacent to each other with the first protrusion part in between, in a second direction perpendicular to the first direction. The first groove part and the third groove part are adjacent to each other with the second protrusion part in between, on an opposite side in a direction in which the second groove part is adjacent to. The first groove part, the second groove part, and the third groove part each have, at opposite ends thereof, openings penetrating the first substrate. The first substrate and the second substrate are stacked in a third direction perpendicular to the first direction and to the second direction, so that the first groove part forms a first flow path, the second groove part forms a second flow path, and the third groove part forms a third flow path.

Inventors

FUJITA, SATOSHI
ZHANG, HUITING
ESPULGAR, Wilfred Villariza
MATSUSAKI, MICHIYA

Assignees

National Institute Of Advanced Industrial Science and Technology

Dates

Publication Date: 20260513
Application Date: 20240517

Claims (11)

A microfluidic chip comprising a first substrate and a second substrate, wherein the first substrate includes: a first groove part extending in a first direction; a second groove part, a portion of which extends in the first direction; a third groove part, a portion of which extends in the first direction; a first protrusion part; and a second protrusion part, the first groove part and the second groove part are adjacent to each other with the first protrusion part in between in a second direction perpendicular to the first direction, the first groove part and the third groove part are adjacent to each other with the second protrusion part in between, on an opposite side in a direction in which the second groove part is adjacent to, the first groove part, the second groove part, and the third groove part each have, at opposite ends thereof, openings penetrating the first substrate, and the first substrate and the second substrate are stacked in a third direction perpendicular to the first direction and to the second direction, so that the first groove part forms a first flow path, the second groove part forms a second flow path, and the third groove part forms a third flow path.
The microfluidic chip according to claim 1, wherein there is a space between the first and the second protrusion parts and the second substrate.
The microfluidic chip according to claim 1, wherein the first groove part further has a third protrusion part.
The microfluidic chip according to claim 3, wherein a height of the third protrusion part is shorter than heights of the first protrusion part and the second protrusion part.
The microfluidic chip according to claim 1, wherein the first protrusion part and the second protrusion part each have a rail-like shape extending in the first direction.
The microfluidic chip according to claim 1, wherein the first protrusion part and the second protrusion part are each in a shape of a plurality of pillars standing in a row in the first direction, the plurality of pillars each having a circular or polygonal cross-section perpendicular to the third direction.
The microfluidic chip according to claim 1, wherein the second substrate is translucent.
The microfluidic chip according to claim 1, wherein the second substrate is oxygen-permeable.
The microfluidic chip according to claim 1, wherein the first substrate is translucent.
The microfluidic chip according to claim 1, wherein the first substrate is oxygen-permeable.
A microphysiological chip manufacturing method comprising: a step of installing the microfluidic chip according to any one of claims 1 to 10 in such a manner that the third direction is a direction opposite from a gravity direction, and the second substrate is on a lower side; a step of injecting, into the first flow path, and gelling a fluid containing at least one type of cells and a gelling agent; and a step of injecting a culture medium solution into the second flow path and the third flow path and carrying out cell culture.

Description

Technical Field The present invention relates to a microfluidic chip, in particular, to a Microphysiological System (MPS) chip. Background Art In recent years, microfluidic chips formed a Microphysiological System (MPS) therein (MPS chips) are attracting attention as an organ model to replace animal testing. An MPS chip, in which an organ tissue and a lumen structure are constructed, is used for a pharmacokinetic analysis or the like by observing molecules entering and exiting at an interface. A commonly MPS chip in one form has a structure in which two or three flow path structures are connected at a central part (see Patent Literature 1, etc.). In the case of two flow paths, an organ is created in one of the flow paths, and a lumen structure is created in the other flow path. In the case of three flow paths, an organ is created in a central channel, and a lumen structure is created on either side thereof. In Patent Literature 1, an MPS chip is formed by providing three flow paths as a relief pattern on a film surface and joining a cover therewith. In Patent Literature 1, cell culture is carried out by using the produced MPS chip so as to observe mass transfer in a Rhodamine perfusion. Citation List Patent Literature Patent Literature 1: Japanese Translation of PCT International Application Publication No. 2021-513856 Summary of Invention Technical Problem However, in the chip disclosed in Patent Literature 1, because the flow paths are provided on the side of a lower layer film, there is a possibility that the relief pattern formed on the lower layer may reduce visibility of the structures when the observation is made from the lower surface of the chip, by using an inverted microscope, an Optical Coherence Tomography (OCT), or the like. Further, when a fence partitioning the flow paths is too high, contact surfaces between two flow paths become small, leading to difficulty of connections at the interface. In view of the above, an object of the present invention is to provide a microfluidic chip having enhanced visibility and connection of an interface structure. Solution to Problem To solve the abovementioned problem, a microfluidic chip of the present invention includes a first substrate and a second substrate. The first substrate includes: a first groove part extending in a first direction; a second groove part, a portion of which extends in the first direction; a third groove part, a portion of which extends in the first direction; a first protrusion part; and a second protrusion part. The first groove part and the second groove part are adjacent to each other with the first protrusion part in between in a second direction perpendicular to the first direction. The first groove part and the third groove part are adjacent to each other with the second protrusion part in between, on an opposite side in a direction in which the second groove part is adjacent to. The first groove part, the second groove part, and the third groove part each have, at opposite ends thereof, openings penetrating the first substrate. The first substrate and the second substrate are stacked in a third direction perpendicular to the first direction and to the second direction, so that the first groove part forms a first flow path, the second groove part forms a second flow path, and the third groove part forms a third flow path. Further, another embodiment of the present invention relates to a microphysiological chip manufacturing method including: a step of installing a microfluidic chip according to the present embodiment in such a manner that the third direction is a direction opposite from a gravity direction, and the second substrate is on a lower side; a step of injecting, into the first flow path, and gelling a fluid containing at least one type of cells and a gelling agent; and a step of injecting a culture medium solution into the second flow path and the third flow path and carrying out cell culture. Advantageous Effects of Invention The present invention is able to provide the microfluidic chip having enhanced visibility and connection of an interface structure. Brief Description of Drawings [Figure 1] Figure 1(a) is an exterior view of a microfluidic chip according to an embodiment of the present invention; Figure 1(b) is a sectional view taken at line Ib-Ib in Figure 1(a); and Figure 1(c) is a sectional view taken at line Ic-Ic in Figure 1(a).[Figure 2] Figure 2(a) is a top view of a microfluidic chip according to Example 1 of the present invention; Figure 2(b) is a top view of the vicinity of a center part of Figure 2(a); and Figure 2(c) is a sectional view taken at line IIc-IIc in Figure 2(a).[Figure 3] Figure 3(a) is a top view of a microfluidic chip according to Example 2 of the present invention; Figure 3(b) is a top view of the vicinity of a center part of Figure 3(a); and Figure 3(c) is a sectional view taken at line IIIc-IIIc in Figure 3(a).[Figure 4] Figure 4(a) is a top view of a microfluidic chip according