Micro-well array chip, method of using the same and detection device
By setting up regular N-sided reaction chambers and virtual idle areas on the microporous array substrate, the chamber layout is optimized, solving the problems of insufficient sensitivity and wasted chamber volume in existing digital PCR chips, and achieving efficient sensitivity improvement and detection limit reduction.
Patent Information
- Authority / Receiving Office
- CN · China
- Patent Type
- Patents(China)
- Current Assignee / Owner
- BOE TECHNOLOGY GROUP CO LTD
- Filing Date
- 2022-04-20
- Publication Date
- 2026-05-01
AI Technical Summary
Existing digital PCR chips have insufficient sensitivity, high detection limits, and significant waste of chamber volume per unit area.
A microporous array chip is designed by setting up regular N-sided reaction chambers and virtual idle areas around them on a microporous array substrate. The chamber layout is optimized to improve the chamber volume utilization, satisfy a specific volume formula, increase the number of reaction chambers, and reduce the detection limit.
This improved the chip's sensitivity, lowered the detection limit, effectively utilized the substrate area, increased the volume of the reaction chamber, and improved detection accuracy.
Smart Images

Figure CN117279714B_ABST
Abstract
Description
Technical Field
[0001] Embodiments of this disclosure relate to a microporous array chip, a method of using the chip, and a detection device thereof. Background Technology
[0002] Polymerase chain reaction (PCR) is a molecular biotechnology that amplifies DNA fragments in vitro. Digital PCR (dPCR) is a new technique for absolute quantification of nucleic acid molecules. It does not rely on a standard curve or reference sample, requires no control, and can directly detect the copy number of the target molecule. The principle of digital PCR is to distribute reagents with low template content into a large number of microwells. After statistical analysis, most wells contain little or no target molecule. After amplification, the initial template amount is counted using an optical detection module. Compared to traditional quantitative PCR, digital PCR technology has higher sensitivity, specificity, high tolerance, and accuracy. This technology has been widely used in the detection of trace amounts of nucleic acid samples, CNV analysis, and gene expression detection in complex samples.
[0003] A microwell array chip is a substrate comprising an array of multiple microwells, each of which can act as a small test tube for detecting or selecting specific compounds from a large number of compounds. Therefore, digital PCR technology can utilize microwell array chips for detection, by squeezing reagents into the chip's channels, thus distributing the reagents to a large number of microwells. Summary of the Invention
[0004] This disclosure provides a microporous array chip, its usage method, and a detection device. The microporous array chip includes a microporous array substrate, which includes a first main surface and a second main surface disposed opposite to each other, n reaction chambers, and a virtual idle region. The n reaction chambers are arrayed within the microporous array substrate, and the virtual idle region surrounds the n reaction chambers. Each reaction chamber is configured to accommodate a sample to be tested. The area of the virtual idle region is divided into n' virtual units. The orthographic projection of each reaction chamber onto a first reference plane containing the first main surface is a regular N-gon, and the orthographic projection of each virtual unit onto the first reference plane is identical to the orthographic projection of the reaction chamber onto the first reference plane. By efficiently utilizing the area of the microporous array substrate, this microporous array chip increases the volume of a single reaction chamber, thereby improving its sensitivity and reducing its detection limit.
[0005] At least one embodiment of this disclosure provides a microporous array chip, comprising: a microporous array substrate including a first main surface and a second main surface disposed opposite to each other; n reaction chambers arrayed in the microporous array substrate and configured to accommodate a sample to be tested, wherein the orthographic projection of each reaction chamber onto a first reference plane containing the first main surface is a regular N-gon; and a virtual idle region disposed around the n reaction chambers; the area of the virtual idle region is divided into n' virtual units, wherein the orthographic projection of each virtual unit onto the first reference plane has the same shape as the orthographic projection of each reaction chamber onto the first reference plane, and the total volume V of the n reaction chambers satisfies the following formula:
[0006]
[0007] Where (1-α) is the confidence level, S chip Let h be the area of the microporous array substrate, h be the depth of the reaction chamber in the direction perpendicular to the first reference plane, N be a positive integer greater than or equal to 3, and X be half the dimension of the line connecting the centers of adjacent reaction chambers.
[0008] For example, a micropore array chip provided in one embodiment of this disclosure further includes a support region configured to provide a support structure, wherein the total volume V of the n reaction chambers satisfies the following formula:
[0009]
[0010] Among them, S support The area of the supporting region.
[0011] For example, a micropore array chip provided in one embodiment of this disclosure further includes: a reaction region disposed around the support region, wherein the n reaction chambers are located in the reaction region.
[0012] For example, in a microporous array chip provided in one embodiment of this disclosure, in the reaction region, the center distance between the orthographic projections of two adjacent reaction chambers on the first reference plane is equal.
[0013] For example, in a microporous array chip provided in an embodiment of this disclosure, the shape of the orthographic projection of the reaction chamber onto the first reference plane where the first main surface is located and the shape of the orthographic projection of the virtual unit onto the first reference plane are both regular hexagons, and the total volume V of the n reaction chambers satisfies the following formula:
[0014]
[0015] Where X ranges from 10 to 20 micrometers, and h ranges from 190 to 320 micrometers.
[0016] For example, in a micro-hole array chip provided in one embodiment of this disclosure, the value of n ranges from 8000 to 100000.
[0017] For example, in a micropore array chip provided in an embodiment of this disclosure, the total volume V of the n reaction chambers satisfies the following formula:
[0018]
[0019] For example, a micropore array chip provided in one embodiment of this disclosure further includes: a first hydrophobic layer located on the first main surface, wherein the orthographic projection of the first hydrophobic layer on the first reference plane is spaced apart from the orthographic projection of the reaction chamber on the first reference plane.
[0020] For example, a micropore array chip provided in one embodiment of this disclosure further includes: a second hydrophobic layer located on the second main surface, the second hydrophobic layer extending to the edge of the reaction chamber.
[0021] For example, a microporous array chip provided in one embodiment of this disclosure further includes: the orthographic projection of the second hydrophobic layer onto a second reference plane where the second main surface is located includes an opening, the edge of the opening coinciding with the edge of the reaction chamber on the second reference plane.
[0022] For example, a microporous array chip provided in one embodiment of this disclosure further includes: a second hydrophobic layer located on the second main surface, the reaction chamber penetrating the microporous array substrate in a direction perpendicular to the first reference plane, the second hydrophobic layer spanning the reaction chamber, and the orthogonal projection of the reaction chamber on the second reference plane where the second main surface is located falling within the orthogonal projection of the second hydrophobic layer on the second reference plane.
[0023] For example, in a microporous array chip provided in an embodiment of this disclosure, the reaction chamber is recessed from the first main surface into the microporous array substrate and has a cavity bottom located within the microporous array substrate, the distance between the cavity bottom and the first reference plane being less than the thickness of the microporous array substrate.
[0024] For example, in a microporous array chip provided in an embodiment of this disclosure, the contact angle between the first hydrophobic layer and the sample to be tested is less than the critical angle of the reaction chamber, wherein the critical angle is the angle between the extension line of the sidewall of the reaction chamber and the tangent of the surface of the sample to be tested that contacts the sidewall of the reaction chamber.
[0025] For example, in a micro-hole array chip provided in one embodiment of this disclosure, the bottom of the cavity includes at least one vent hole, and each vent hole penetrates the bottom of the cavity in a direction perpendicular to the first reference plane.
[0026] For example, in a micro-hole array chip provided in an embodiment of this disclosure, the bottom of the cavity includes an exhaust hole, and the orthographic projection of the exhaust hole on the second reference plane where the second main surface is located is located at the center of the orthographic projection of the bottom of the cavity on the second reference plane.
[0027] For example, in a micro-hole array chip provided in an embodiment of this disclosure, the bottom of the cavity includes a plurality of exhaust holes, and the orthographic projection of the exhaust holes on the second reference plane where the second main surface is located is arranged around the center of the orthographic projection of the bottom of the cavity on the second reference plane.
[0028] For example, a microporous array chip provided in one embodiment of this disclosure further includes: a dialysis membrane; and a second hydrophobic layer, wherein the reaction chamber extends through the microporous array substrate in a direction perpendicular to the first reference plane, the second hydrophobic layer extends to the edge of the reaction chamber, and the dialysis membrane spans the reaction chamber.
[0029] For example, in a microporous array chip provided in an embodiment of this disclosure, the orthographic projection of the reaction chamber on the second reference plane where the second main surface is located falls within the orthographic projection of the dialysis membrane on the second reference plane.
[0030] For example, in a microporous array chip provided in one embodiment of this disclosure, the dialysis membrane is a flexible dialysis membrane.
[0031] For example, in a microporous array chip provided in one embodiment of this disclosure, the dialysis membrane is located on the side of the second hydrophobic layer near the second main surface.
[0032] For example, in a microporous array chip provided in one embodiment of this disclosure, the dialysis membrane is located on the side of the second hydrophobic layer away from the second main surface.
[0033] For example, in a microporous array chip provided in one embodiment of this disclosure, the angle between the inner surface of the reaction chamber and the first main surface is greater than 90 degrees.
[0034] For example, in a microporous array chip provided in an embodiment of this disclosure, the inner surface of the reaction chamber includes a first sub-surface and a second sub-surface in a direction perpendicular to the first reference plane. The second sub-surface is located on the side of the first sub-surface away from the first main surface. The angle between the first sub-surface and the first main surface is greater than 90 degrees, and the angle between the second sub-surface and the second main surface is greater than 90 degrees.
[0035] For example, in a microporous array chip provided in an embodiment of this disclosure, the inner surface of the reaction chamber includes a first sub-surface, a second sub-surface, and a third sub-surface in a direction perpendicular to the first reference plane. The second sub-surface is located on the side of the first sub-surface away from the first main surface, and the third sub-surface is located on the side of the second sub-surface away from the first sub-surface. The angle between the first sub-surface and the first main surface is greater than 90 degrees. The plane containing the second sub-surface is perpendicular to the first reference plane, and the angle between the third sub-surface and the second main surface is greater than 90 degrees.
[0036] For example, in a micro-hole array chip provided in an embodiment of this disclosure, the inner surface of the reaction chamber includes a first sub-surface, a second sub-surface, and a third sub-surface in a direction perpendicular to the first reference plane. The second sub-surface is located on the side of the first sub-surface away from the first main surface, and the third sub-surface is located on the side of the second sub-surface away from the first sub-surface. The angle between the first sub-surface and the first main surface is greater than 90 degrees. The second sub-surface is an arc surface and is recessed into the micro-hole array substrate. The angle between the third sub-surface and the second main surface is greater than 90 degrees.
[0037] For example, in a microporous array chip provided in an embodiment of this disclosure, a first hydrophilic membrane and a second hydrophilic membrane are disposed on the inner surface of the reaction chamber. The first hydrophilic membrane and the second hydrophilic membrane are disposed adjacent to each other in a direction perpendicular to the first reference plane. The surface of the first hydrophilic membrane away from the inner surface of the reaction chamber is an arc surface protruding toward the central axis of the reaction chamber, and the surface of the second hydrophilic membrane away from the inner surface of the reaction chamber is an arc surface protruding toward the central axis of the reaction chamber.
[0038] For example, in a microporous array chip provided in an embodiment of this disclosure, the inner surface of the reaction chamber is a plane, the thickness of the first hydrophilic membrane is different in the direction perpendicular to the inner surface, so that the surface of the first hydrophilic membrane away from the inner surface of the reaction chamber is an arc surface, and the thickness of the second hydrophilic membrane is different in the direction perpendicular to the inner surface, so that the surface of the second hydrophilic membrane away from the inner surface of the reaction chamber is an arc surface.
[0039] For example, in a microporous array chip provided in an embodiment of this disclosure, the inner surface of the reaction chamber includes a first sub-surface and a second sub-surface in a direction perpendicular to the first reference plane. The second sub-surface is located on the side of the first sub-surface away from the first main surface. The first sub-surface protrudes toward the central axis of the reaction chamber, such that the surface of the first hydrophilic membrane away from the inner surface of the reaction chamber is an arc surface. The second sub-surface protrudes toward the central axis of the reaction chamber, such that the surface of the second hydrophilic membrane away from the inner surface of the reaction chamber is an arc surface.
[0040] For example, in a micro-hole array chip provided in one embodiment of this disclosure, the shape of the orthographic projection of the reaction chamber onto the first reference plane is virtually one of a circle, a regular hexagon, or a regular octagon.
[0041] For example, in a microporous array chip provided in one embodiment of this disclosure, the shape of the orthographic projection of the reaction chamber onto the first reference plane is virtually a triangle.
[0042] For example, a micro-pore array chip provided in one embodiment of this disclosure further includes: a first encapsulation film located on the side of the first main surface away from the second main surface; and a second encapsulation film located on the side of the second main surface away from the first main surface, wherein the first encapsulation film and the second encapsulation film are attached to the micro-pore array substrate by electrostatic or adhesive bonding.
[0043] For example, a microporous array chip provided in one embodiment of this disclosure further includes: a photocurable oil located at the opening of the reaction chamber near the first main surface, the photocurable oil including a boss structure, the boss structure being disposed in contact with the first main surface and located on the side of the first hydrophobic layer near the central axis of the reaction chamber.
[0044] For example, in a micro-hole array chip provided in one embodiment of this disclosure, the micro-hole array substrate is a flexible substrate.
[0045] For example, in a microporous array chip provided in an embodiment of this disclosure, the microporous array substrate further includes: a liquid inlet channel, n reaction chambers connected to the liquid inlet channel, and a one-way membrane disposed between each reaction chamber and the liquid inlet channel.
[0046] For example, in a microporous array chip provided in one embodiment of this disclosure, the liquid inlet channel includes: a main liquid inlet channel; and n branch liquid inlet channels, which are respectively connected to the main liquid inlet channel, and the n branch liquid inlet channels and the n reaction chambers are arranged in a one-to-one correspondence.
[0047] For example, in a microporous array chip provided in an embodiment of this disclosure, the microporous array substrate further includes: a liquid inlet channel, comprising a plurality of interconnected sub-liquid inlet channels, wherein the plurality of sub-liquid inlet channels have different heights and each sub-liquid inlet channel is connected to a plurality of reaction chambers.
[0048] For example, in a micropore array chip provided in one embodiment of this disclosure, the heights of the plurality of sub-inlet channels decrease sequentially.
[0049] For example, in a micropore array chip provided in one embodiment of this disclosure, the height of the plurality of liquid inlet channels decreases sequentially from the middle to both sides.
[0050] For example, a micro-hole array chip provided in one embodiment of this disclosure further includes: a first substrate located on one side of the micro-hole array substrate and spaced apart from the first main surface; and a second substrate located on the side of the micro-hole array substrate away from the first substrate, the second substrate including a heating electrode, the orthographic projection of the heating electrode on the first reference plane overlapping the orthographic projection of at least a portion of the n reaction chambers on the first reference plane.
[0051] For example, in a micro-hole array chip provided in one embodiment of this disclosure, the first substrate includes: a first substrate; and a third hydrophobic layer located on the side of the first substrate close to the second substrate.
[0052] For example, in a micro-hole array chip provided in an embodiment of this disclosure, the second substrate further includes: a second substrate; a control electrode located on the second substrate; a first insulating layer located on the side of the control electrode away from the second substrate; and a second insulating layer, wherein the first insulating layer includes a connection hole that exposes at least a portion of the control electrode, the heating electrode is located on the side of the first insulating layer away from the second substrate and is connected to the control electrode through the connection hole, the second insulating layer is located on the side of the heating electrode away from the first insulating layer, and the micro-hole array substrate is located on the second insulating layer.
[0053] For example, a microporous array chip provided in one embodiment of this disclosure further includes: a photosensitive sensor located on the side of the second substrate away from the first substrate, the photosensitive sensor being configured to detect light emitted from the reaction chamber in the microporous array substrate.
[0054] At least one embodiment of this disclosure also provides a detection device, including the micropore array chip described in any of the preceding claims.
[0055] For example, one embodiment of the detection device provided in this disclosure further includes: a first housing located on one side of the microporous array chip and spaced apart from the microporous array chip; and a second housing located on the side of the microporous array chip away from the first housing and spaced apart from the microporous array chip, wherein the distance between the microporous array chip and the second housing is greater than or equal to the thickness of the microporous array chip.
[0056] For example, in a detection device provided in one embodiment of this disclosure, the second housing includes a support structure, the support structure includes a first platform portion and a second platform portion, the height of the second platform portion is greater than the height of the first platform portion, the first platform portion is configured to contact the bottom surface of the micro-hole array chip, and the second platform portion is configured to contact the side surface of the micro-hole array chip.
[0057] For example, in a detection device provided in an embodiment of this disclosure, the shape of the orthographic projection of the first platform portion on the first main surface includes an arc triangle, and the shape of the orthographic projection of the second platform portion on the first main surface includes a semicircle. The base of the arc triangle connected to the semicircle is a straight line, and the other two sides of the arc triangle are arcs.
[0058] For example, in a detection device provided in one embodiment of this disclosure, the second housing further includes a positioning frustum configured to contact the side of the micro-hole array chip.
[0059] At least one embodiment of this disclosure also provides a method of using a microporous array chip, the microporous array chip including a microporous array substrate, the method comprising: introducing a sample to be tested into the microporous array substrate; encapsulating the sample to be tested in the microporous array substrate, the microporous array substrate including n reaction chambers and an idle region, the n reaction chambers being arrayed in the microporous array substrate and configured to accommodate the sample to be tested; the orthographic projection of the reaction chambers onto a first reference plane containing a first main surface is a regular N-gon, the idle region being disposed around the n reaction chambers; the area of the idle region being divided into n' virtual units, the orthographic projection of the virtual units onto the first reference plane having the same shape as the orthographic projection of the reaction chambers onto the first reference plane, the total volume V of the n reaction chambers satisfying the following formula:
[0060]
[0061] Where (1-α) is the confidence level, S chipLet h be the area of the microporous array substrate, h be the depth of the reaction chamber in the direction perpendicular to the first reference plane, N be a positive integer greater than or equal to 3, and X be half the dimension of the line connecting the centers of adjacent reaction chambers.
[0062] For example, in a method of using a microporous array chip provided in an embodiment of this disclosure, encapsulating the sample to be tested in the microporous array substrate includes: after introducing the sample to be tested into the microporous array substrate, attaching a first encapsulation film to the side of the first main surface away from the second main surface by electrostatics or colloid, and attaching a second encapsulation film to the side of the second main surface away from the first main surface.
[0063] For example, in a method of using a microporous array chip provided in an embodiment of this disclosure, encapsulating the sample to be tested in the microporous array substrate includes: after introducing the sample to be tested into the microporous array substrate, coating a photocurable oil at the opening position of the reaction chamber near the first main surface; and curing the photocurable oil with ultraviolet light.
[0064] For example, in a method of using a microporous array chip provided in an embodiment of this disclosure, the microporous array substrate includes a first sub-flexible microporous array substrate and a second sub-flexible microporous array substrate, and a plurality of sample flow channels are included between the first sub-flexible microporous array substrate and the second sub-flexible microporous array substrate. Passing a sample to be tested into the microporous array substrate includes passing the sample to be tested into the plurality of sample flow channels.
[0065] For example, a method of using the microporous array chip provided in one embodiment of this disclosure further includes: introducing the sample to be tested into the plurality of sample channels by means of vacuuming.
[0066] For example, in a method of using a microporous array chip provided in an embodiment of this disclosure, encapsulating the sample to be tested in the microporous array substrate includes: using rollers to separate each of the sample channels to form multiple reaction chambers, and sealing the multiple reaction chambers. Attached Figure Description
[0067] To more clearly illustrate the technical solutions of the embodiments of this disclosure, the accompanying drawings of the embodiments will be briefly described below. Obviously, the drawings described below only relate to some embodiments of this disclosure and are not intended to limit this disclosure.
[0068] Figure 1 This is a planar schematic diagram of a micro-hole array chip provided in one embodiment of the present disclosure;
[0069] Figure 2 This is a cross-sectional schematic diagram of a micro-hole array chip provided in an embodiment of the present disclosure;
[0070] Figure 3A A planar schematic diagram of the reaction chamber in another microporous array chip provided in an embodiment of this disclosure;
[0071] Figure 3B A cross-sectional schematic diagram of the reaction chamber in another microporous array chip provided in an embodiment of this disclosure;
[0072] Figure 4A This is a cross-sectional schematic diagram of another micro-hole array chip provided in an embodiment of the present disclosure;
[0073] Figure 4B This is a cross-sectional schematic diagram of another micro-hole array chip provided in an embodiment of the present disclosure;
[0074] Figure 5 This is a cross-sectional schematic diagram of another micro-hole array chip provided in an embodiment of the present disclosure;
[0075] Figure 6A A planar schematic diagram of another micro-hole array chip provided in an embodiment of this disclosure;
[0076] Figure 6B This is a cross-sectional schematic diagram of another micro-hole array chip provided in an embodiment of the present disclosure;
[0077] Figure 7A A planar schematic diagram of another micro-hole array chip provided in an embodiment of this disclosure;
[0078] Figure 7B This is a cross-sectional schematic diagram of another micro-hole array chip provided in an embodiment of the present disclosure;
[0079] Figure 8A A planar schematic diagram of another micro-hole array chip provided in an embodiment of this disclosure;
[0080] Figure 8B This is a cross-sectional schematic diagram of another micro-hole array chip provided in an embodiment of the present disclosure;
[0081] Figure 9A A planar schematic diagram of another micro-hole array chip provided in an embodiment of this disclosure;
[0082] Figure 9B This is a cross-sectional schematic diagram of another micro-hole array chip provided in an embodiment of the present disclosure;
[0083] Figure 10A A planar schematic diagram of another micro-hole array chip provided in an embodiment of this disclosure;
[0084] Figure 10B This is a cross-sectional schematic diagram of another micro-hole array chip provided in an embodiment of the present disclosure;
[0085] Figure 11A This is a cross-sectional schematic diagram of another micro-hole array chip provided in an embodiment of the present disclosure;
[0086] Figure 11B A three-dimensional schematic diagram of a reaction chamber in a microporous array chip provided in an embodiment of this disclosure;
[0087] Figure 11C A three-dimensional schematic diagram of a reaction chamber in a microporous array chip provided in an embodiment of this disclosure;
[0088] Figure 12A This is a cross-sectional schematic diagram of another micro-hole array chip provided in an embodiment of the present disclosure;
[0089] Figure 12B A three-dimensional schematic diagram of a reaction chamber in a microporous array chip provided in an embodiment of this disclosure;
[0090] Figure 12C A three-dimensional schematic diagram of a reaction chamber in a microporous array chip provided in an embodiment of this disclosure;
[0091] Figure 13A This is a cross-sectional schematic diagram of another micro-hole array chip provided in an embodiment of the present disclosure;
[0092] Figure 13B A three-dimensional schematic diagram of a reaction chamber in a microporous array chip provided in an embodiment of this disclosure;
[0093] Figure 13C A three-dimensional schematic diagram of a reaction chamber in a microporous array chip provided in an embodiment of this disclosure;
[0094] Figure 14A This is a cross-sectional schematic diagram of another micro-hole array chip provided in an embodiment of the present disclosure;
[0095] Figure 14B A three-dimensional schematic diagram of a reaction chamber in a microporous array chip provided in an embodiment of this disclosure;
[0096] Figure 14C A three-dimensional schematic diagram of a reaction chamber in a microporous array chip provided in an embodiment of this disclosure;
[0097] Figure 15 This is a cross-sectional schematic diagram of another micro-hole array chip provided in an embodiment of the present disclosure;
[0098] Figure 16 This is a cross-sectional schematic diagram of another micro-hole array chip provided in an embodiment of the present disclosure;
[0099] Figure 17This is a schematic diagram of the structure of a micro-hole array chip provided in an embodiment of the present disclosure;
[0100] Figure 18 This is a cross-sectional schematic diagram of another micro-hole array chip provided in an embodiment of the present disclosure;
[0101] Figure 19 This is a cross-sectional schematic diagram of another micro-hole array chip provided in an embodiment of the present disclosure;
[0102] Figure 20 A planar schematic diagram of another micro-hole array chip provided in an embodiment of this disclosure;
[0103] Figure 21 A planar schematic diagram of another micro-hole array chip provided in an embodiment of this disclosure;
[0104] Figure 22 A planar schematic diagram of another micro-hole array chip provided in an embodiment of this disclosure;
[0105] Figure 23 A planar schematic diagram of another micro-hole array chip provided in an embodiment of this disclosure;
[0106] Figure 24 This is a cross-sectional schematic diagram of another micro-hole array chip provided in an embodiment of the present disclosure;
[0107] Figure 25 This is a cross-sectional schematic diagram of another micro-hole array chip provided in an embodiment of the present disclosure;
[0108] Figure 26 This is a cross-sectional schematic diagram of another micro-hole array chip provided in an embodiment of the present disclosure;
[0109] Figure 27 This is a schematic diagram of a detection device provided in one embodiment of the present disclosure;
[0110] Figure 28 A schematic diagram of another detection device provided in an embodiment of this disclosure; and
[0111] Figure 29 This is a plan view of the second housing in a detection device provided in an embodiment of the present disclosure. Detailed Implementation
[0112] To make the objectives, technical solutions, and advantages of the embodiments of this disclosure clearer, the technical solutions of the embodiments of this disclosure will be clearly and completely described below with reference to the accompanying drawings. Obviously, the described embodiments are only some, not all, of the embodiments of this disclosure. All other embodiments obtained by those skilled in the art based on the described embodiments of this disclosure without creative effort are within the scope of protection of this disclosure.
[0113] Unless otherwise defined, the technical or scientific terms used in this disclosure shall have the ordinary meaning understood by one of ordinary skill in the art to which this disclosure pertains. The terms “first,” “second,” and similar terms used in this disclosure do not indicate any order, quantity, or importance, but are merely used to distinguish different components. Terms such as “comprising” or “including” mean that an element or object preceding the word encompasses the elements or objects listed following the word and their equivalents, without excluding other elements or objects. Terms such as “connected” or “linked” are not limited to physical or mechanical connections, but can include electrical connections, whether direct or indirect.
[0114] Unless otherwise defined, the features such as "parallel," "perpendicular," and "identical" used in the embodiments of this disclosure include strictly defined cases of "parallel," "perpendicular," and "identical," as well as cases involving a certain degree of error, such as "approximately parallel," "approximately perpendicular," and "approximately identical." For example, the aforementioned "approximately" may indicate that the difference between the compared objects is within 10% or 5% of the average value of the compared objects. Unless otherwise specified in the following embodiments of this disclosure, the quantity of a component or element is implied to mean that the component or element may be one or more, or can be understood as at least one. "At least one" refers to one or more, and "more" refers to at least two. In the embodiments of this disclosure, "same-layer arrangement" refers to the relationship between multiple film layers formed from the same material after undergoing the same step (e.g., a patterning process). Here, "same-layer" does not always mean that the multiple film layers have the same thickness or that the multiple film layers have the same height in a cross-sectional view.
[0115] In their research, the inventors of this application noted that the main problem with current digital PCR chips is how to improve sensitivity and how to lower the chip's detection limit. From a chemical perspective, the larger the volume of a single chamber, the more complete the reaction will be, as the more abundant the sample. On the other hand, if the volume of a single reaction chamber is too large, it will result in a waste of chamber volume per unit area of the chip. Therefore, the size of the reaction chamber needs to be controlled within a certain range.
[0116] This disclosure provides a microporous array chip, its usage method, and a detection device. The microporous array chip includes a microporous array substrate, which includes a first main surface and a second main surface disposed opposite to each other, n reaction chambers, and an idle area. The n reaction chambers are arrayed within the microporous array substrate, and the idle area surrounds the n reaction chambers. The reaction chambers are configured to accommodate a sample to be tested. The orthographic projection of each reaction chamber onto a first reference plane containing the first main surface is positive. The area of the idle area is divided into n' virtual units. The orthographic projections of the reaction chambers onto the first reference plane containing the first main surface and the orthographic projections of the virtual units onto the first reference plane are both regular N-gons. The total volume V of the n reaction chambers satisfies the following formula:
[0117]
[0118] Where (1-α) is the confidence level, S chip denoted as the area of the micro-hole array substrate, h as the depth of the reaction chamber in the direction perpendicular to the first reference plane, N as a positive integer greater than or equal to 3, and X as half the dimension of the line connecting the centers of adjacent reaction chambers.
[0119] In the microporous array chip provided in the embodiments of this disclosure, since the total volume V of the n reaction chambers satisfies the above formula, the microporous array chip can efficiently utilize the area of the microporous array substrate, thereby increasing the volume of a single reaction chamber under the premise that the number of reaction chambers is sufficient, thereby improving the sensitivity of the microporous array chip and reducing the detection limit of the microporous array chip.
[0120] The micro-hole array chip, its usage method, and detection device provided in the embodiments of this disclosure will now be described in detail with reference to the accompanying drawings.
[0121] One embodiment of this disclosure provides a micro-hole array chip. Figure 1 This is a planar schematic diagram of a micro-hole array chip provided in one embodiment of this disclosure. Figure 2 This is a cross-sectional schematic diagram of a micro-hole array chip provided in an embodiment of the present disclosure.
[0122] like Figure 1 and Figure 2As shown, the microporous array chip 100 includes a microporous array substrate 110; the microporous array substrate 110 includes a first main surface 110A and a second main surface 110B disposed opposite to each other, n reaction chambers 120 and an idle region 130; the n reaction chambers 120 are arrayed in the microporous array substrate 110, and the idle region 130 is disposed around the n reaction chambers 120; the reaction chambers 120 are configured to accommodate the sample to be tested, and the orthographic projection of the reaction chambers 120 on the first reference plane 201 where the first main surface 110A is located is a regular N-gon; the area of the idle region 130 is divided into n' virtual units 132, and the orthographic projection shape of the virtual units 132 on the first reference plane 201 is the same as the orthographic projection shape of the reaction chambers 120 on the first reference plane 201; the total volume V of the n reaction chambers 120 satisfies the following formula:
[0123]
[0124] Where (1-α) is the confidence level, S chip Let be the area of the micro-hole array substrate 110, h be the depth of the reaction chamber 120 in the direction perpendicular to the first reference plane 201, N be a positive integer greater than or equal to 3, and X be half the dimension of the spacing between adjacent reaction chambers 120 along the line connecting the centers of the adjacent reaction chambers 120. It should be noted that when N is infinitely large, the aforementioned regular N-gon can be circular; additionally, Figure 1 The size and number of reaction chambers in the microporous array substrate shown are only illustrative; the number of reaction chambers can be set according to actual needs.
[0125] In the microporous array chip provided in the embodiments of this disclosure, since the total volume V of the n reaction chambers satisfies the above formula, the microporous array chip can efficiently utilize the area of the microporous array substrate, thereby increasing the volume of a single reaction chamber under the premise that the number of reaction chambers is sufficient, thereby improving the sensitivity of the microporous array chip and reducing the detection limit of the microporous array chip.
[0126] In some examples, the total volume V of the n reaction chambers satisfies the following formula:
[0127]
[0128] Therefore, this micro-hole array chip can efficiently utilize the area of the micro-hole array substrate, improve the sensitivity of the micro-hole array chip, and reduce the detection limit of the micro-hole array chip.
[0129] In some examples, such as Figure 1 and Figure 2As shown, the microporous array chip 110 also includes a support region 140, which is configured to provide a support structure. At this time, the total volume V of the n reaction chambers 120 satisfies the following formula:
[0130]
[0131] Among them, S support To support an area of 140.
[0132] In the microporous array chip provided in this example, the support region can be used to contact a support structure (e.g., the support structure of a base), thereby creating a certain gap between the microporous array substrate and the base to facilitate the entry of liquid (e.g., the sample to be tested), thus allowing the microporous array substrate to be oil-sealed. It should be noted that... Figure 1 The supporting areas may use different filling patterns, but the material of the supporting areas can be the same as that of the other areas; that is, the surface of the supporting area can be the same as the surface of the surrounding unused areas. Of course, the embodiments of this disclosure include, but are not limited to, other materials or structures that may be coated on the surface of the supporting area that contacts the supporting structure, or surface treatments may be applied to increase friction or other properties for better contact with the supporting structure.
[0133] In some examples, such as Figure 1 and Figure 2 As shown, the microporous array chip 100 also includes a reaction region 150; the reaction region 150 is disposed around the support region 140, and n reaction chambers 120 are disposed within the reaction region 150. Thus, the support region of the microporous array chip does not have reaction chambers, and the reaction region is disposed around the support region, which can fully utilize the area of the microporous array substrate.
[0134] For example, such as Figure 1 and Figure 2 As shown, four support regions 140 are located at the four edges of the microporous array substrate 110, and are respectively located at the middle of the edges; the reaction region 150 is disposed in the middle region of the microporous array substrate 110, and is located around the support regions 140.
[0135] It should be noted that in the microvia array chip provided in this embodiment, the virtual units are set up to calculate the area of the idle area and the area occupied by the reaction chamber as units. Therefore, the virtual units and the reaction chambers not only have the same shape, but also have the same arrangement. For example, the spacing between adjacent virtual units and reaction chambers, the spacing between adjacent reaction chambers, and the spacing between adjacent virtual units can all be the same. For another example, when the reaction chambers are arranged in a certain period to form a reaction chamber group (e.g., a reaction chamber row or a reaction chamber column), the virtual units can also be arranged in a certain period to form a virtual group. For yet another example, when the reaction chambers are arranged regularly or staggered due to their shape, the virtual units are also arranged regularly or staggered to fill the reaction area and idle area on the entire microvia array substrate. It is worth noting that when the microvia array chip includes a support area, the virtual units only need to avoid the support area; the arrangement of the virtual units in the idle area remains the same as the arrangement of the reaction chambers.
[0136] In some examples, such as Figure 1 and Figure 2 As shown, in the reaction region 150, the center distance between the orthographic projections of two adjacent reaction chambers 120 onto the first reference plane 201 is equal. That is, the barriers between adjacent reaction chambers in the reaction region are equal and uniformly distributed. Therefore, this microporous array chip ensures that the volume of liquid (e.g., the sample to be tested) entering each reaction chamber is consistent, resulting in more precise reactions.
[0137] In some examples, such as Figure 1 and Figure 2 As shown, the orthographic projection of each reaction chamber 120 onto the first reference plane 201 is a regular hexagon, which allows for easier entry of liquid (e.g., the sample to be tested) into the reaction chamber while maintaining a large volume. Of course, embodiments of this disclosure include, but are not limited to, the orthographic projection of each reaction chamber 120 onto the first reference plane 201 can also be a circle, a regular octagon, a regular pentagon, a square, or a triangle, etc.
[0138] For example, the shape of the orthographic projection of each reaction chamber onto the first reference plane can be triangular. Since the angles of each triangle are small, the surface tension of the sample under test can be disrupted, thus making it easier for the test sample to enter the reaction chamber.
[0139] In some examples, such as Figure 1 and Figure 2 As shown, the shape of the orthographic projection of the reaction chamber 120 onto the first reference plane 201 where the first main surface 110A is located, and the shape of the orthographic projection of the virtual unit 132 onto the first reference plane 201 are both regular hexagons. The total volume V of the n reaction chambers satisfies the following formula:
[0140]
[0141] Where X ranges from 10 to 20 micrometers, and h ranges from 190 to 320 micrometers.
[0142] In the microporous array chip provided in this example, the shape of the orthographic projection of each reaction chamber on the first reference plane is a regular hexagon. Since the total volume V of the n reaction chambers satisfies the above formula, the microporous array chip can efficiently utilize the area of the microporous array substrate, thereby increasing the volume of a single reaction chamber, which in turn can improve the sensitivity of the microporous array chip and reduce the detection limit of the microporous array chip.
[0143] In some examples, the spacing between adjacent reaction chambers 120 on the line connecting the centers of the adjacent reaction chambers 120 can range from 20 to 40 micrometers, for example, 24 micrometers, 26 micrometers, 28 micrometers, 30 micrometers, 32 micrometers, 34 micrometers or 36 micrometers.
[0144] In some examples, the depth of the reaction chamber 120 in the direction perpendicular to the first reference plane 201 may be 200 micrometers, 220 micrometers, 240 micrometers, 260 micrometers, 280 micrometers or 300 micrometers.
[0145] In some examples, the number of reaction chambers 120 on a microporous array substrate 110 can be 8,000-100,000. As a result, the microporous array chip has higher detection accuracy.
[0146] In some examples, the number of reaction chambers 120 on a micropore array substrate 110 may be 8,000, 10,000, 20,000, 40,000, 60,000, 80,000, or 100,000.
[0147] Figure 3A A planar schematic diagram of the reaction chamber in another microporous array chip provided in an embodiment of this disclosure; Figure 3B This is a cross-sectional schematic diagram of the reaction chamber in another microporous array chip provided in an embodiment of the present disclosure.
[0148] like Figure 3A and 3BAs shown, the microporous array chip 100 also includes a first hydrophobic layer 161, which is disposed on the first main surface 110A. The orthographic projection of the first hydrophobic layer 161 on the first reference plane 201 is spaced apart from the orthographic projection of the reaction chamber 120 on the first reference plane 201. That is, the first hydrophobic layer 161 does not extend to the edge of the reaction chamber 120, thereby preventing samples or reagents from remaining outside the reaction chamber while facilitating the entry of samples or reagents into the reaction chamber. It should be noted that the first hydrophobic layer has hydrophobic and oleophilic properties, which makes it easier for liquids (such as the sample to be tested) to enter the reaction chambers defined by the microporous array substrate.
[0149] For example, the material of the first hydrophobic layer can be a resin or a silicon nitride, such as epoxy resin. The first hydrophobic layer can also be prepared using other suitable inorganic or organic materials, as long as the side of the first hydrophobic layer away from the microporous array substrate is hydrophobic.
[0150] In some examples, such as Figure 3A and 3B As shown, the orthographic projection of the first hydrophobic layer 161 onto the first reference plane 201 where the first main surface 110A is located includes a first opening 1610. The edge of the first opening 1610 is spaced apart from the edge of the reaction chamber 120 on the first reference plane 201 and is located outside the edge of the reaction chamber 120 on the first reference plane 201.
[0151] In some examples, such as Figure 3A As shown, the shape of the orthographic projection of the reaction chamber 120 onto the first reference plane 201 is a regular hexagon, the shape of the first opening 1610 is a regular hexagon, and the side length of the first opening 1610 is greater than the side length of the orthographic projection of the reaction chamber 120 onto the first reference plane 201.
[0152] In some examples, such as Figure 3A and 3B As shown, in this micro-hole array chip 100, the reaction chamber 120 penetrates the micro-hole array substrate 110 in a direction perpendicular to the micro-hole array substrate 110 (that is, in a direction perpendicular to the first reference plane 201). In other words, the reaction chamber 120 is a through hole penetrating the micro-hole array substrate 110.
[0153] In some examples, such as Figure 3A and 3B As shown, the microporous array chip 100 also includes a second hydrophobic layer 162; the second hydrophobic layer 162 is located on the second main surface 110B; the second hydrophobic layer 162 extends to the edge of the reaction chamber 120. It should be noted that the second hydrophobic layer has hydrophobic and oleophilic properties, thereby making it easier for liquids (such as the sample to be tested) to enter the reaction chambers defined by the microporous array substrate.
[0154] For example, the material of the second hydrophobic layer can be a resin or a silicon nitride, such as epoxy resin. The second hydrophobic layer can also be prepared using other suitable inorganic or organic materials, as long as the side of the second hydrophobic layer away from the microporous array substrate is hydrophobic.
[0155] In some examples, such as Figure 3A and 3B As shown, the orthographic projection of the second hydrophobic layer 162 onto the second reference plane 202 where the second main surface 110B is located includes a second opening 1620, the edge of which coincides with the edge of the reaction chamber 120 on the second reference plane 202. That is, the second hydrophobic layer is located exactly between adjacent reaction chambers.
[0156] In some examples, such as Figure 3A As shown, the shape of the orthographic projection of the reaction chamber 120 onto the first reference plane 201 is a regular hexagon, the shape of the second opening 1620 is a regular hexagon, and the side length of the second opening 1620 is equal to the side length of the orthographic projection of the reaction chamber 120 onto the first reference plane 201.
[0157] Figure 4A This is a cross-sectional schematic diagram of another micro-hole array chip provided in an embodiment of the present disclosure; Figure 4B This is a cross-sectional schematic diagram of another micro-hole array chip provided in an embodiment of the present disclosure.
[0158] like Figure 4A and Figure 4B As shown, in this micro-hole array chip 100, the reaction chamber 120 penetrates the micro-hole array substrate 110 in a direction perpendicular to the micro-hole array substrate 110 (that is, in a direction perpendicular to the first reference plane 201). In other words, the reaction chamber 120 is a through hole penetrating the micro-hole array substrate 110.
[0159] In some examples, such as Figure 4A and 4B As shown, the microporous array chip 100 also includes a first hydrophobic layer 161, which is disposed on the first main surface 110A. The orthographic projection of the first hydrophobic layer 161 on the first reference plane 201 is spaced apart from the orthographic projection of the reaction chamber 120 on the first reference plane 201. That is, the first hydrophobic layer 161 does not extend to the edge of the reaction chamber 120, thereby preventing samples or reagents from remaining outside the reaction chamber while facilitating the entry of samples or reagents into the reaction chamber. It should be noted that the first hydrophobic layer has hydrophobic and oleophilic properties, which makes it easier for liquids (such as the sample to be tested) to enter the reaction chambers defined by the microporous array substrate.
[0160] For example, the material of the first hydrophobic layer can be a resin or a silicon nitride, such as epoxy resin. The first hydrophobic layer can also be prepared using other suitable inorganic or organic materials, as long as the side of the first hydrophobic layer away from the microporous array substrate is hydrophobic.
[0161] In some examples, such as Figure 4A and 4B As shown, the orthographic projection of the first hydrophobic layer 161 onto the first reference plane 201 where the first main surface 110A is located includes a first opening 1610. The edge of the first opening 1610 is spaced apart from the edge of the reaction chamber 120 on the first reference plane 201 and is located outside the edge of the reaction chamber 120 on the first reference plane 201.
[0162] In some examples, such as Figure 4A and 4B As shown, the microporous array chip 100 also includes a second hydrophobic layer 162 located on the second main surface 110B. The second hydrophobic layer 162 spans the reaction chamber 120, and the orthographic projection of the reaction chamber 120 on the second reference plane 202 of the second main surface 110B falls within the orthographic projection of the second hydrophobic layer 162 on the second reference plane 202. In other words, the microporous array chip can seal the side of the reaction chamber located on the second main surface through the second hydrophobic layer, thereby forming a blind via in the reaction chamber.
[0163] In some examples, such as Figure 4A As shown, the shape of the orthographic projection of the reaction chamber 120 onto the first reference plane 201 is a regular hexagon; at this time, the shape of the first opening 1610 of the orthographic projection of the first hydrophobic layer 161 onto the first reference plane 201 is also a regular hexagon, and the side length of the first opening 1610 is greater than the side length of the orthographic projection of the reaction chamber 120 onto the first reference plane 201.
[0164] Figure 5 This is a cross-sectional schematic diagram of another micro-hole array chip provided in an embodiment of this disclosure. (See diagram below.) Figure 5 As shown, the reaction chamber 120 is recessed from the first main surface 110A into the micro-hole array substrate 110 and has a cavity bottom 122 located within the micro-hole array substrate 110. The distance between the cavity bottom 122 and the first reference plane 201 is less than the thickness of the micro-hole array substrate 110. That is, the reaction chamber is a blind hole.
[0165] In some examples, such as Figure 5 As shown, the microporous array chip 100 also includes a first hydrophobic layer 161, which is disposed on the first main surface 110A. The contact angle θ between the first hydrophobic layer 161 and the sample to be tested is... e The critical angle θ is less than 120° of the reaction chamber. t0 Critical angle θe The angle is defined as the angle between the extension of the sidewall of the reaction chamber 120 and the tangent to the surface of the sample in contact with the sidewall of the reaction chamber 120. This allows the microporous array chip to better facilitate the entry of the sample into the reaction chamber.
[0166] In some examples, such as Figure 5 As shown, two adjacent reaction chambers 120 are arranged along a first direction. The dimension of the sidewall between two adjacent reaction chambers 120 along the first direction on the first reference plane 201 is Wtt, and the dimension of the sidewall between two adjacent reaction chambers 120 along the first direction on the second reference plane 202 is Wtb. The orthographic projection of the bottom 122 of the reaction chamber 120 onto the second reference plane 202 along the first direction is St. The angle between the sidewall of the reaction chamber 120 and the direction perpendicular to the second reference plane 202 is α. t At this point, the critical angle θ of the reaction chamber t0 Satisfy the following formula:
[0167]
[0168] Figure 6A A planar schematic diagram of another micro-hole array chip provided in an embodiment of this disclosure; Figure 6B This is a cross-sectional schematic diagram of another micro-hole array chip provided in an embodiment of the present disclosure.
[0169] like Figure 6A and 6B As shown, the reaction chamber 120 is recessed from the first main surface 110A into the micro-hole array substrate 110 and has a cavity bottom 122 located within the micro-hole array substrate 110. The distance between the cavity bottom 122 and the first reference plane 201 is less than the thickness of the micro-hole array substrate 110. That is, the reaction chamber is a blind hole.
[0170] In some examples, such as Figure 6A and Figure 6B As shown, the bottom 122 of the cavity includes at least one vent 1220, each vent 1220 penetrating the bottom 122 of the cavity in a direction perpendicular to the first reference plane 201. Thus, when liquid (e.g., the sample to be tested) enters the reaction chamber, the vent can be used to expel gas, thereby making it easier for the liquid to enter the reaction chamber and increasing the speed at which the liquid enters the reaction chamber.
[0171] In some examples, such as Figure 6A and Figure 6BAs shown, the bottom 122 of the chamber includes an exhaust port 1220, and the orthographic projection of the exhaust port 1220 on the second reference plane 202 where the second main surface 110B is located is at the center of the orthographic projection of the bottom 122 of the chamber onto the second reference plane 202. Thus, air can be rapidly discharged from the exhaust port of the reaction chamber, thereby increasing the rate at which liquid (e.g., the sample to be tested) enters the reaction chamber.
[0172] In some examples, such as Figure 6A and 6B As shown, the microporous array chip 100 also includes a first hydrophobic layer 161, which is disposed on the first main surface 110A. The orthographic projection of the first hydrophobic layer 161 on the first reference plane 201 is spaced apart from the orthographic projection of the reaction chamber 120 on the first reference plane 201. That is, the first hydrophobic layer 161 does not extend to the edge of the reaction chamber 120, thereby preventing samples or reagents from remaining outside the reaction chamber while facilitating the entry of samples or reagents into the reaction chamber. It should be noted that the first hydrophobic layer has hydrophobic and oleophilic properties, which makes it easier for liquids (such as the sample to be tested) to enter the reaction chambers defined by the microporous array substrate.
[0173] For example, the material of the first hydrophobic layer can be a resin or a silicon nitride, such as epoxy resin. The first hydrophobic layer can also be prepared using other suitable inorganic or organic materials, as long as the side of the first hydrophobic layer away from the microporous array substrate is hydrophobic.
[0174] In some examples, such as Figure 6A and 6B As shown, the orthographic projection of the first hydrophobic layer 161 onto the first reference plane 201 where the first main surface 110A is located includes a first opening 1610. The edge of the first opening 1610 is spaced apart from the edge of the reaction chamber 120 on the first reference plane 201 and is located outside the edge of the reaction chamber 120 on the first reference plane 201.
[0175] In some examples, such as Figure 6A and 6B As shown, the microporous array chip 100 also includes a second hydrophobic layer 162 located on the second main surface 110B; the second hydrophobic layer 162 also includes an exhaust opening 1625, which is connected to the exhaust hole 1220 mentioned above.
[0176] Figure 7A A planar schematic diagram of another micro-hole array chip provided in an embodiment of this disclosure; Figure 7B This is a cross-sectional schematic diagram of another micro-hole array chip provided in an embodiment of the present disclosure.
[0177] like Figure 7A and 7BAs shown, the reaction chamber 120 is recessed from the first main surface 110A into the micro-hole array substrate 110 and has a cavity bottom 122 located within the micro-hole array substrate 110. The distance between the cavity bottom 122 and the first reference plane 201 is less than the thickness of the micro-hole array substrate 110. That is, the reaction chamber is a blind hole.
[0178] In some examples, such as Figure 7A and Figure 7B As shown, the bottom 122 of the chamber includes multiple vent holes 1220, each vent hole 1220 penetrating the bottom 122 of the chamber in a direction perpendicular to the first reference plane 201. The orthographic projections of the multiple vent holes 1220 on the second reference plane 202, where the second main surface 110B is located, are arranged around the center of the orthographic projection of the bottom 122 of the chamber on the second reference plane 202. Thus, when liquid (e.g., the sample to be tested) enters the reaction chamber, the multiple vent holes can be used simultaneously for gas discharge, thereby making it easier for liquid to enter the reaction chamber and increasing the speed at which liquid enters the reaction chamber.
[0179] In some examples, such as Figure 7A As shown, the orthographic projection of the reaction chamber 120 onto the second reference plane 202 is a regular hexagon; at this time, the orthographic projections of the six exhaust holes 1220 onto the second reference plane 202 are set at the six corners of the orthographic projection of the reaction chamber 120 onto the second reference plane 202.
[0180] In some examples, such as Figure 7A and 7B As shown, the microporous array chip 100 also includes a first hydrophobic layer 161, which is disposed on the first main surface 110A. The orthographic projection of the first hydrophobic layer 161 on the first reference plane 201 is spaced apart from the orthographic projection of the reaction chamber 120 on the first reference plane 201. That is, the first hydrophobic layer 161 does not extend to the edge of the reaction chamber 120, thereby preventing samples or reagents from remaining outside the reaction chamber while facilitating the entry of samples or reagents into the reaction chamber.
[0181] In some examples, such as Figure 7A and 7B As shown, the orthographic projection of the first hydrophobic layer 161 onto the first reference plane 201 where the first main surface 110A is located includes a first opening 1610. The edge of the first opening 1610 is spaced apart from the edge of the reaction chamber 120 on the first reference plane 201 and is located outside the edge of the reaction chamber 120 on the first reference plane 201.
[0182] In some examples, such as Figure 7A and 7BAs shown, the microporous array chip 100 also includes a second hydrophobic layer 162 located on the second main surface 110B; the second hydrophobic layer 162 includes a plurality of venting openings 1625, the plurality of venting openings 1625 and the plurality of venting openings 1220 are arranged in a one-to-one correspondence, and each venting opening 1625 is connected to the corresponding venting hole 1220.
[0183] Figure 8A A planar schematic diagram of another micro-hole array chip provided in an embodiment of this disclosure; Figure 8B This is a cross-sectional schematic diagram of another micro-hole array chip provided in an embodiment of the present disclosure.
[0184] like Figure 8A and Figure 8B As shown, in the micro-hole array chip 100, the reaction chamber 120 penetrates the micro-hole array substrate 110 in a direction perpendicular to the micro-hole array substrate 110 (that is, in a direction perpendicular to the first reference plane 201). In other words, the reaction chamber 120 is a through hole penetrating the micro-hole array substrate 110.
[0185] In some examples, such as Figure 8A and 8B As shown, the microporous array chip 100 also includes a first hydrophobic layer 161, which is disposed on the first main surface 110A. The orthographic projection of the first hydrophobic layer 161 on the first reference plane 201 is spaced apart from the orthographic projection of the reaction chamber 120 on the first reference plane 201. That is, the first hydrophobic layer 161 does not extend to the edge of the reaction chamber 120, thereby preventing samples or reagents from remaining outside the reaction chamber while facilitating the entry of samples or reagents into the reaction chamber.
[0186] In some examples, such as Figure 8A and 8B As shown, the orthographic projection of the first hydrophobic layer 161 onto the first reference plane 201 where the first main surface 110A is located includes a first opening 1610. The edge of the first opening 1610 is spaced apart from the edge of the reaction chamber 120 on the first reference plane 201 and is located outside the edge of the reaction chamber 120 on the first reference plane 201.
[0187] In some examples, such as Figure 8A and Figure 8BAs shown, the microporous array chip 100 also includes a dialysis membrane 170 and a second hydrophobic layer 162; the reaction chamber 120 extends through the microporous array substrate 110 in a direction perpendicular to the first reference plane 201, the second hydrophobic layer 162 extends to the edge of the reaction chamber 120, and the dialysis membrane 170 spans the reaction chamber 120. Thus, the dialysis membrane allows gas to escape from the reaction chamber but does not allow liquid to flow out, thereby increasing the rate at which liquid (e.g., the sample to be tested) enters the reaction chamber while preventing liquid from flowing out of the reaction chamber.
[0188] In some examples, such as Figure 8A and Figure 8B As shown, the orthographic projection of the reaction chamber 120 on the second reference plane 202, where the second main surface 110B is located, falls within the orthographic projection of the dialysis membrane 170 on the second reference plane 202.
[0189] In some examples, such as Figure 8A and Figure 8B As shown, the dialysis membrane 170 is a flexible dialysis membrane. When the dialysis membrane is flexible, it can better contact the liquid (e.g., the sample to be tested), thereby venting the gas in the reaction chamber. Of course, the embodiments of this disclosure include, but are not limited to, this, and the dialysis membrane can also be a thin film with a certain degree of rigidity.
[0190] Figure 9A A planar schematic diagram of another micro-hole array chip provided in an embodiment of this disclosure; Figure 9B This is a cross-sectional schematic diagram of another micro-hole array chip provided in an embodiment of the present disclosure.
[0191] like Figure 9A and Figure 9B As shown, in the micro-hole array chip 100, the reaction chamber 120 penetrates the micro-hole array substrate 110 in a direction perpendicular to the micro-hole array substrate 110 (that is, in a direction perpendicular to the first reference plane 201). In other words, the reaction chamber 120 is a through hole penetrating the micro-hole array substrate 110.
[0192] In some examples, such as Figure 9A and 9B As shown, the microporous array chip 100 also includes a first hydrophobic layer 161, which is disposed on the first main surface 110A. The orthographic projection of the first hydrophobic layer 161 on the first reference plane 201 is spaced apart from the orthographic projection of the reaction chamber 120 on the first reference plane 201. That is, the first hydrophobic layer 161 does not extend to the edge of the reaction chamber 120, thereby preventing samples or reagents from remaining outside the reaction chamber while facilitating the entry of samples or reagents into the reaction chamber.
[0193] In some examples, such as Figure 9A and9B As shown, the orthographic projection of the first hydrophobic layer 161 onto the first reference plane 201 where the first main surface 110A is located includes a first opening 1610. The edge of the first opening 1610 is spaced apart from the edge of the reaction chamber 120 on the first reference plane 201 and is located outside the edge of the reaction chamber 120 on the first reference plane 201.
[0194] In some examples, such as Figure 9A and Figure 9B As shown, the microporous array chip 100 also includes a dialysis membrane 170 and a second hydrophobic layer 162; the reaction chamber 120 extends through the microporous array substrate 110 in a direction perpendicular to the first reference plane 201, the second hydrophobic layer 162 extends to the edge of the reaction chamber 120, and the dialysis membrane 170 spans the reaction chamber 120. The dialysis membrane 170 is located on the side of the second hydrophobic layer 162 near the second main surface 110B.
[0195] Figure 10A A planar schematic diagram of another micro-hole array chip provided in an embodiment of this disclosure; Figure 10B This is a cross-sectional schematic diagram of another micro-hole array chip provided in an embodiment of the present disclosure.
[0196] like Figure 10A and Figure 10B As shown, in the micro-hole array chip 100, the reaction chamber 120 penetrates the micro-hole array substrate 110 in a direction perpendicular to the micro-hole array substrate 110 (that is, in a direction perpendicular to the first reference plane 201). In other words, the reaction chamber 120 is a through hole penetrating the micro-hole array substrate 110.
[0197] In some examples, such as Figure 10A and 10B As shown, the microporous array chip 100 also includes a first hydrophobic layer 161, which is disposed on the first main surface 110A. The orthographic projection of the first hydrophobic layer 161 on the first reference plane 201 is spaced apart from the orthographic projection of the reaction chamber 120 on the first reference plane 201. That is, the first hydrophobic layer 161 does not extend to the edge of the reaction chamber 120, thereby preventing samples or reagents from remaining outside the reaction chamber while facilitating the entry of samples or reagents into the reaction chamber.
[0198] In some examples, such as Figure 10A and 10B As shown, the orthographic projection of the first hydrophobic layer 161 onto the first reference plane 201 where the first main surface 110A is located includes a first opening 1610. The edge of the first opening 1610 is spaced apart from the edge of the reaction chamber 120 on the first reference plane 201 and is located outside the edge of the reaction chamber 120 on the first reference plane 201.
[0199] In some examples, such as Figure 10A and Figure 10B As shown, the microporous array chip 100 also includes a dialysis membrane 170 and a second hydrophobic layer 162; the reaction chamber 120 extends through the microporous array substrate 110 in a direction perpendicular to the first reference plane 201, the second hydrophobic layer 162 extends to the edge of the reaction chamber 120, and the dialysis membrane 170 spans the reaction chamber 120. The dialysis membrane 170 is located on the side of the second hydrophobic layer 162 away from the second main surface 110B.
[0200] Figure 11A This is a cross-sectional schematic diagram of another micro-hole array chip provided in an embodiment of the present disclosure; Figure 11B A three-dimensional schematic diagram of a reaction chamber in a microporous array chip provided in an embodiment of this disclosure; Figure 11C This is a three-dimensional schematic diagram of a reaction chamber in a microporous array chip provided in an embodiment of the present disclosure.
[0201] like Figure 11A , Figure 11B and Figure 11C As shown, in the micro-hole array chip 100, the reaction chamber 120 penetrates the micro-hole array substrate 110 in a direction perpendicular to the micro-hole array substrate 110 (that is, in a direction perpendicular to the first reference plane 201). In other words, the reaction chamber 120 is a through hole penetrating the micro-hole array substrate 110.
[0202] In some examples, such as Figure 11A As shown, the microporous array chip 100 also includes a first hydrophobic layer 161, which is disposed on the first main surface 110A. The orthographic projection of the first hydrophobic layer 161 on the first reference plane 201 is spaced apart from the orthographic projection of the reaction chamber 120 on the first reference plane 201. That is, the first hydrophobic layer 161 does not extend to the edge of the reaction chamber 120, thereby preventing samples or reagents from remaining outside the reaction chamber while facilitating the entry of samples or reagents into the reaction chamber.
[0203] In some examples, such as Figure 11A As shown, the microporous array chip 100 also includes a second hydrophobic layer 162; the second hydrophobic layer 162 is located on the second main surface 110B; the second hydrophobic layer 162 extends to the edge of the reaction chamber 120.
[0204] In some examples, such as Figure 11A , Figure 11B and Figure 11CAs shown, the angle γ between the inner surface 126 of the reaction chamber 120 and the first main surface 110A is greater than 90 degrees. That is, the portion of the reaction chamber 120 closest to the first main surface 110A has a larger dimension. Therefore, this reaction chamber facilitates the entry of liquid, thereby increasing the speed at which liquid (e.g., the sample to be tested) enters the reaction chamber.
[0205] In some examples, such as Figure 11B As shown, the cross-section of the reaction chamber 120 cut by the first reference plane 201 where the first main surface 110A is located is circular; the cross-section of the reaction chamber 120 cut by the second reference plane 202 where the second main surface 110B is located is circular; and the diameter of the cross-section of the reaction chamber 120 cut by the first reference plane 201 is greater than the diameter of the cross-section of the reaction chamber 120 cut by the second reference plane 202.
[0206] In some examples, such as Figure 11C As shown, the cross-section of the reaction chamber 120 cut by the first reference plane 201 where the first main surface 110A is located is a regular hexagon; the cross-section of the reaction chamber 120 cut by the second reference plane 202 where the second main surface 110B is located is a regular hexagon; and the side length of the cross-section of the reaction chamber 120 cut by the first reference plane 201 is greater than the side length of the cross-section of the reaction chamber 120 cut by the second reference plane 202.
[0207] Figure 12A This is a cross-sectional schematic diagram of another micro-hole array chip provided in an embodiment of the present disclosure; Figure 12B A three-dimensional schematic diagram of a reaction chamber in a microporous array chip provided in an embodiment of this disclosure; Figure 12C This is a three-dimensional schematic diagram of a reaction chamber in a microporous array chip provided in an embodiment of the present disclosure.
[0208] like Figure 12A , Figure 12B and Figure 12C As shown, in the micro-hole array chip 100, the reaction chamber 120 penetrates the micro-hole array substrate 110 in a direction perpendicular to the micro-hole array substrate 110 (that is, in a direction perpendicular to the first reference plane 201). In other words, the reaction chamber 120 is a through hole penetrating the micro-hole array substrate 110.
[0209] In some examples, such as Figure 12AAs shown, the microporous array chip 100 also includes a first hydrophobic layer 161, which is disposed on the first main surface 110A. The orthographic projection of the first hydrophobic layer 161 on the first reference plane 201 is spaced apart from the orthographic projection of the reaction chamber 120 on the first reference plane 201. That is, the first hydrophobic layer 161 does not extend to the edge of the reaction chamber 120, thereby preventing samples or reagents from remaining outside the reaction chamber while facilitating the entry of samples or reagents into the reaction chamber.
[0210] In some examples, such as Figure 12A As shown, the microporous array chip 100 also includes a second hydrophobic layer 162; the second hydrophobic layer 162 is located on the second main surface 110B; the second hydrophobic layer 162 extends to the edge of the reaction chamber 120.
[0211] In some examples, such as Figure 12A , Figure 12B and Figure 12C As shown, the inner surface 126 of the reaction chamber 120 includes a first sub-surface 1261 and a second sub-surface 1262 in a direction perpendicular to the first reference plane 201. The second sub-surface 1262 is located on the side of the first sub-surface 1261 away from the first main surface 110A. The angle between the first sub-surface 1261 and the first main surface 110A is greater than 90 degrees, and the angle between the second sub-surface 1262 and the second main surface 110B is greater than 90 degrees. That is, the portion of the reaction chamber 120 near the first main surface 110A has a larger size, the portion of the reaction chamber 120 near the second main surface 110B has a larger size, and the portion in the middle of the reaction chamber 120 has a smaller size. Therefore, this reaction chamber facilitates both the entry of liquid and the expulsion of gas, thereby further increasing the speed at which liquid (e.g., the sample to be tested) enters the reaction chamber.
[0212] In some examples, such as Figure 12B As shown, the cross-section of the reaction chamber 120 cut by the first reference plane 201 where the first main surface 110A is located is circular; the cross-section of the reaction chamber 120 cut by the second reference plane 202 where the second main surface 110B is located is circular; the cross-section of the reaction chamber 120 cut by the third reference plane 203, which is parallel to the first reference plane 201 and the second reference plane 202 and located at the first reference plane 201 and the second reference plane 202, is circular; and the diameters of the cross-sections of the reaction chamber 120 cut by the first reference plane 201 and the second reference plane 202 are both greater than the diameter of the cross-section of the reaction chamber 120 cut by the third reference plane 203, which is parallel to the first reference plane 201 and the second reference plane 202 and located at the first reference plane 201 and the second reference plane 202.
[0213] In some examples, such as Figure 12C As shown, the cross-section of the reaction chamber 120 cut by the first reference plane 201 where the first main surface 110A is located is a regular hexagon; the cross-section of the reaction chamber 120 cut by the second reference plane 202 where the second main surface 110B is located is a regular hexagon; the cross-section of the reaction chamber 120 cut by the third reference plane 203, which is parallel to the first reference plane 201 and the second reference plane 202 and located on the first reference plane 201 and the second reference plane 202, is a regular hexagon; and the side lengths of the cross-sections of the reaction chamber 120 cut by the first reference plane 201 and the second reference plane 202 are both greater than the side length of the cross-section of the reaction chamber 120 cut by the third reference plane 203.
[0214] Figure 13A This is a cross-sectional schematic diagram of another micro-hole array chip provided in an embodiment of the present disclosure; Figure 13B A three-dimensional schematic diagram of a reaction chamber in a microporous array chip provided in an embodiment of this disclosure; Figure 13C This is a three-dimensional schematic diagram of a reaction chamber in a microporous array chip provided in an embodiment of the present disclosure.
[0215] like Figure 13A , Figure 13B and Figure 13C As shown, in the micro-hole array chip 100, the reaction chamber 120 penetrates the micro-hole array substrate 110 in a direction perpendicular to the micro-hole array substrate 110 (that is, in a direction perpendicular to the first reference plane 201). In other words, the reaction chamber 120 is a through hole penetrating the micro-hole array substrate 110.
[0216] In some examples, such as Figure 13A As shown, the microporous array chip 100 also includes a first hydrophobic layer 161, which is disposed on the first main surface 110A. The orthographic projection of the first hydrophobic layer 161 on the first reference plane 201 is spaced apart from the orthographic projection of the reaction chamber 120 on the first reference plane 201. That is, the first hydrophobic layer 161 does not extend to the edge of the reaction chamber 120, thereby preventing samples or reagents from remaining outside the reaction chamber while facilitating the entry of samples or reagents into the reaction chamber.
[0217] In some examples, such as Figure 13A As shown, the microporous array chip 100 also includes a second hydrophobic layer 162; the second hydrophobic layer 162 is located on the second main surface 110B; the second hydrophobic layer 162 extends to the edge of the reaction chamber 120.
[0218] In some examples, such as Figure 13A , Figure 13B and Figure 13C As shown, the inner surface 126 of the reaction chamber 120 includes a first sub-surface 1261, a second sub-surface 1262, and a third sub-surface 1263 in a direction perpendicular to the first reference plane 201. The second sub-surface 1262 is located on the side of the first sub-surface 1261 away from the first main surface 110A, and the third sub-surface 1263 is located on the side of the second sub-surface 1262 away from the first sub-surface 1261. The angle between the first sub-surface 1261 and the first main surface 110A is greater than 90 degrees, the plane of the second sub-surface 1262 is perpendicular to the first reference plane 201, and the angle between the third sub-surface 1263 and the second main surface 110B is greater than 90 degrees. In this case, the portion of the reaction chamber 120 near the first main surface 110A has a larger size, the portion of the reaction chamber 120 near the second main surface 110B has a larger size, and the portion in the middle of the reaction chamber 120 has a smaller size. Therefore, this reaction chamber facilitates both the entry of liquid and the exit of gas, thereby further increasing the rate at which liquid (e.g., the sample to be tested) enters the reaction chamber. Furthermore, since the plane of the second sub-surface is perpendicular to the first reference plane, the center of the reaction chamber is convenient for storing liquid.
[0219] In some examples, such as Figure 13B As shown, the cross-section of the reaction chamber 120 cut by the first reference plane 201 where the first main surface 110A is located is circular; the cross-section of the reaction chamber 120 cut by the second reference plane 202 where the second main surface 110B is located is circular; the cross-section of the reaction chamber 120 cut by the third reference plane 203, which is parallel to the first reference plane 201 and the second reference plane 202 and located at the first reference plane 201 and the second reference plane 202, is circular; and the diameters of the cross-sections of the reaction chamber 120 cut by the first reference plane 201 and the second reference plane 202 are both greater than the diameter of the cross-section of the reaction chamber 120 cut by the third reference plane 203, which is parallel to the first reference plane 201 and the second reference plane 202 and located at the first reference plane 201 and the second reference plane 202.
[0220] In some examples, such as Figure 13CAs shown, the cross-section of the reaction chamber 120 cut by the first reference plane 201 where the first main surface 110A is located is a regular hexagon; the cross-section of the reaction chamber 120 cut by the second reference plane 202 where the second main surface 110B is located is a regular hexagon; the cross-section of the reaction chamber 120 cut by the third reference plane 203, which is parallel to the first reference plane 201 and the second reference plane 202 and located on the first reference plane 201 and the second reference plane 202, is a regular hexagon; and the side lengths of the cross-sections of the reaction chamber 120 cut by the first reference plane 201 and the second reference plane 202 are both greater than the side length of the cross-section of the reaction chamber 120 cut by the third reference plane 203.
[0221] Figure 14A This is a cross-sectional schematic diagram of another micro-hole array chip provided in an embodiment of the present disclosure; Figure 14B A three-dimensional schematic diagram of a reaction chamber in a microporous array chip provided in an embodiment of this disclosure; Figure 14C This is a three-dimensional schematic diagram of a reaction chamber in a microporous array chip provided in an embodiment of the present disclosure.
[0222] like Figure 14A , Figure 14B and Figure 14C As shown, in the micro-hole array chip 100, the reaction chamber 120 penetrates the micro-hole array substrate 110 in a direction perpendicular to the micro-hole array substrate 110 (that is, in a direction perpendicular to the first reference plane 201). In other words, the reaction chamber 120 is a through hole penetrating the micro-hole array substrate 110.
[0223] In some examples, such as Figure 14A As shown, the microporous array chip 100 also includes a first hydrophobic layer 161, which is disposed on the first main surface 110A. The orthographic projection of the first hydrophobic layer 161 on the first reference plane 201 is spaced apart from the orthographic projection of the reaction chamber 120 on the first reference plane 201. That is, the first hydrophobic layer 161 does not extend to the edge of the reaction chamber 120, thereby preventing samples or reagents from remaining outside the reaction chamber while facilitating the entry of samples or reagents into the reaction chamber.
[0224] In some examples, such as Figure 14A As shown, the microporous array chip 100 also includes a second hydrophobic layer 162; the second hydrophobic layer 162 is located on the second main surface 110B; the second hydrophobic layer 162 extends to the edge of the reaction chamber 120.
[0225] In some examples, such as Figure 14A , Figure 14B and Figure 14CAs shown, the inner surface 126 of the reaction chamber 120 includes a first sub-surface 1261, a second sub-surface 1262, and a third sub-surface 1263 in a direction perpendicular to the first reference plane 201. The second sub-surface 1262 is located on the side of the first sub-surface 1261 away from the first main surface 110A, and the third sub-surface 1263 is located on the side of the second sub-surface 1262 away from the first sub-surface 1261. The angle between the first sub-surface 1261 and the first main surface 110A is greater than 90 degrees. The second sub-surface 1262 is an arc surface and is recessed into the micro-hole array substrate 110. The angle between the third sub-surface 1263 and the second main surface 110B is greater than 90 degrees. In this case, the portion of the reaction chamber 120 near the first main surface 110A has a larger size, the portion of the reaction chamber 120 near the second main surface 110B has a larger size, and the portion in the middle of the reaction chamber 120 has a smaller size. Therefore, this reaction chamber facilitates both the entry of liquid and the exit of gas, thereby further increasing the speed at which liquid (e.g., the sample to be tested) enters the reaction chamber. Furthermore, since the second sub-surface is an arc surface and recessed into the microporous array substrate, the center of the reaction chamber is convenient for storing liquid.
[0226] In some examples, such as Figure 14B As shown, the cross-section of the reaction chamber 120 cut by the first reference plane 201 where the first main surface 110A is located is circular; the cross-section of the reaction chamber 120 cut by the second reference plane 202 where the second main surface 110B is located is circular; the cross-section of the reaction chamber 120 cut by the third reference plane 203, which is parallel to the first reference plane 201 and the second reference plane 202 and located at the first reference plane 201 and the second reference plane 202, is circular; and the diameters of the cross-sections of the reaction chamber 120 cut by the first reference plane 201 and the second reference plane 202 are both greater than the diameter of the cross-section of the reaction chamber 120 cut by the third reference plane 203, which is parallel to the first reference plane 201 and the second reference plane 202 and located at the first reference plane 201 and the second reference plane 202.
[0227] In some examples, such as Figure 14CAs shown, the cross-section of the reaction chamber 120 cut by the first reference plane 201 where the first main surface 110A is located is a regular hexagon; the cross-section of the reaction chamber 120 cut by the second reference plane 202 where the second main surface 110B is located is a regular hexagon; the cross-section of the reaction chamber 120 cut by the third reference plane 203, which is parallel to the first reference plane 201 and the second reference plane 202 and located on the first reference plane 201 and the second reference plane 202, is a regular hexagon; and the side lengths of the cross-sections of the reaction chamber 120 cut by the first reference plane 201 and the second reference plane 202 are both greater than the side length of the cross-section of the reaction chamber 120 cut by the third reference plane 203.
[0228] Figure 15 This is a cross-sectional schematic diagram of another micro-hole array chip provided in an embodiment of this disclosure. (See diagram below.) Figure 15 As shown, in the micro-hole array chip 100, the reaction chamber 120 penetrates the micro-hole array substrate 110 in a direction perpendicular to the micro-hole array substrate 110 (i.e., perpendicular to the first reference plane 201). In other words, the reaction chamber 120 is a through-hole penetrating the micro-hole array substrate 110. A first hydrophilic film 181 and a second hydrophilic film 182 are disposed on the inner surface 126 of the reaction chamber 120. The first hydrophilic film 181 and the second hydrophilic film 182 are disposed adjacent to each other in a direction perpendicular to the first reference plane 201. The surface of the first hydrophilic film 181 away from the inner surface 126 of the reaction chamber 120 is an arc-shaped surface protruding towards the central axis of the reaction chamber 120, and the surface of the second hydrophilic film 182 away from the inner surface 126 of the reaction chamber 120 is also an arc-shaped surface protruding towards the central axis of the reaction chamber 120. Thus, on the one hand, the first and second hydrophilic membranes facilitate the entry of liquids (such as the sample to be tested) into the reaction chamber and are conducive to liquid storage; on the other hand, the inner surface of the first hydrophilic membrane away from the reaction chamber is an arc-shaped surface convex towards the central axis of the reaction chamber, making the portion of the reaction chamber near the first main surface larger, which is more conducive to the entry of liquids into the reaction chamber; similarly, the inner surface of the second hydrophilic membrane away from the reaction chamber is arc-shaped, making the portion of the reaction chamber near the second main surface larger, which is conducive to gas discharge; at the same time, a recessed portion (i.e., the portion adjacent to the first and second hydrophilic membranes) can be formed between the first and second hydrophilic membranes, which is more conducive to the storage of liquids.
[0229] In some examples, such as Figure 15As shown, the inner surface 126 of the reaction chamber 120 is a plane. The thickness of the first hydrophilic membrane 181 varies in the direction perpendicular to the inner surface 126, so that the surface of the first hydrophilic membrane 181 away from the inner surface 126 of the reaction chamber 120 is an arc surface. The thickness of the second hydrophilic membrane 182 varies in the direction perpendicular to the inner surface 126, so that the surface of the second hydrophilic membrane 182 away from the inner surface of the reaction chamber 120 is an arc surface.
[0230] Figure 16 This is a cross-sectional schematic diagram of another micro-hole array chip provided in an embodiment of this disclosure. (See diagram below.) Figure 16 As shown, in the micro-hole array chip 100, the reaction chamber 120 penetrates the micro-hole array substrate 110 in a direction perpendicular to the micro-hole array substrate 110 (that is, in a direction perpendicular to the first reference plane 201). In other words, the reaction chamber 120 is a through hole penetrating the micro-hole array substrate 110. A first hydrophilic membrane 181 and a second hydrophilic membrane 182 are disposed on the inner surface 126 of the reaction chamber 120. The first hydrophilic membrane 181 and the second hydrophilic membrane 182 are disposed adjacent to each other in a direction perpendicular to the first reference plane 201. The inner surface 126 of the reaction chamber 120 includes a first sub-surface 1261 and a second sub-surface 1262 in a direction perpendicular to the first reference plane 201. The second sub-surface 1262 is located on the side of the first sub-surface 1261 away from the first main surface 110A. The first sub-surface 1261 protrudes toward the central axis of the reaction chamber 120, so that the surface of the first hydrophilic membrane 181 away from the inner surface 126 of the reaction chamber 120 is an arc surface. The second sub-surface 1262 protrudes toward the central axis of the reaction chamber 120, so that the surface of the second hydrophilic membrane 182 away from the inner surface 126 of the reaction chamber 120 is an arc surface. Thus, on the one hand, the first and second hydrophilic membranes facilitate the entry of liquids (such as the sample to be tested) into the reaction chamber and are conducive to liquid storage; on the other hand, the inner surface of the first hydrophilic membrane away from the reaction chamber is an arc-shaped surface convex towards the central axis of the reaction chamber, making the portion of the reaction chamber near the first main surface larger, which is more conducive to the entry of liquids into the reaction chamber; similarly, the inner surface of the second hydrophilic membrane away from the reaction chamber is arc-shaped, making the portion of the reaction chamber near the second main surface larger, which is conducive to gas discharge; at the same time, a recessed portion (i.e., the portion adjacent to the first and second hydrophilic membranes) can be formed between the first and second hydrophilic membranes, which is more conducive to the storage of liquids.
[0231] Figure 17 This is a schematic diagram of a micro-hole array chip provided in one embodiment of the present disclosure. Figure 17As shown, the microporous array chip 100 further includes a first encapsulation film 191 and a second encapsulation film 192; the first encapsulation film 191 is located on the side of the first main surface 110A away from the second main surface 110B; the second encapsulation film 192 is located on the side of the second main surface 110B away from the first main surface 110A; the first encapsulation film 191 and the second encapsulation film 192 are attached to the microporous array substrate 110 by electrostatic adsorption or adhesive bonding. Therefore, the microporous array chip is relatively convenient to use. After a liquid (e.g., a sample to be tested) is introduced into the microporous array substrate, the first and second encapsulation films can be attached to the microporous array substrate by electrostatic adsorption or adhesive bonding.
[0232] In some examples, such as Figure 17 As shown, the microporous array chip 100 further includes a first hydrophobic layer 161 and a second hydrophobic layer 162. The first hydrophobic layer 161 is disposed on the first main surface 110A. The orthographic projection of the first hydrophobic layer 161 on the first reference plane 201 is spaced apart from the orthographic projection of the reaction chamber 120 on the first reference plane 201. The second hydrophobic layer 162 is located on the second main surface 110B. At this time, the first encapsulation film 191 is located on the side of the first hydrophobic layer 161 away from the second main surface 110B; the second encapsulation film 192 is located on the side of the second hydrophobic layer 162 away from the first main surface 110A. Thus, the first and second encapsulation films can better encapsulate the microporous array substrate. Furthermore, the first hydrophobic layer has hydrophobic and oleophilic properties, thereby allowing liquids (e.g., samples to be tested) to more easily enter the reaction chambers defined by the microporous array substrate.
[0233] For example, the materials for the first and second hydrophobic layers can be resins or silicon nitrides, such as epoxy resins. The first and second hydrophobic layers can also be prepared using other suitable inorganic or organic materials.
[0234] Figure 18 This is a cross-sectional schematic diagram of another micro-hole array chip provided in an embodiment of this disclosure. (See diagram below.) Figure 18 As shown, the microporous array chip 100 also includes a photocurable varnish 210; the photocurable varnish 210 is located at the opening of the reaction chamber 120 near the first main surface 110A. Thus, the microporous array chip can encapsulate the reaction chamber using the photocurable varnish. It should be noted that the photocurable varnish can be first introduced into the opening of the reaction chamber near the first main surface, and then cured using a photocuring process, thereby encapsulating the reaction chamber.
[0235] In some examples, such as Figure 18As shown, the microporous array chip 100 also includes a first hydrophobic layer 161, which is disposed on the first main surface 110A. The orthographic projection of the first hydrophobic layer 161 on the first reference plane 201 is spaced apart from the orthographic projection of the reaction chamber 120 on the first reference plane 201. That is, the first hydrophobic layer 161 does not extend to the edge of the reaction chamber 120, thereby preventing samples or reagents from remaining outside the reaction chamber while facilitating the entry of samples or reagents into the reaction chamber.
[0236] In some examples, such as Figure 18 As shown, the UV-curing oil 210 includes a boss structure 212, which is disposed in contact with the first main surface 110A and is located on the side of the first hydrophobic layer 161 near the central axis of the reaction chamber 120.
[0237] Figure 19 This is a cross-sectional schematic diagram of another micro-hole array chip provided in an embodiment of this disclosure. (See diagram below.) Figure 19 As shown, the microporous array substrate 110 is a flexible substrate. In this case, the microporous array substrate 110 may include a first sub-flexible microporous array substrate 115A and a second sub-flexible microporous array substrate 115B. The first sub-flexible microporous array substrate 115A and the second sub-flexible microporous array substrate 115B are in contact and are arranged together, and a plurality of reaction chambers 120 are formed between the first sub-flexible microporous array substrate 115A and the second flexible microporous array substrate 115B.
[0238] Figure 20 This is a planar schematic diagram of another micro-hole array chip provided in an embodiment of this disclosure. Figure 20 As shown, the microporous array substrate 110 includes a liquid inlet channel 128; n reaction chambers 120 are connected to the liquid inlet channel 128, and a one-way membrane 129 is disposed between each reaction chamber 120 and the liquid inlet channel 128. Thus, the microporous array chip can introduce liquid (e.g., a sample to be tested) into the reaction chambers through the liquid inlet channel, while the one-way membrane prevents the sample in the reaction chamber from returning to the liquid inlet channel, thereby preventing crosstalk between different reaction chambers. Of course, embodiments of this disclosure include, but are not limited to, the one-way membrane between each reaction chamber and the liquid inlet channel may not be provided.
[0239] In some examples, such as Figure 20 As shown, the liquid inlet channel 128 includes a main liquid inlet channel 1282 and n branch liquid inlet channels 1284, each connected to the main liquid inlet channel 1282; the n branch liquid inlet channels 1284 and the n reaction chambers 120 are arranged in a one-to-one correspondence. Thus, the microporous array chip can introduce liquid (e.g., the sample to be tested) into the reaction chambers through the main liquid inlet channel and the branch liquid inlet channels.
[0240] In some examples, such as Figure 20As shown, n inlet branch channels 1284 are arranged on both sides of the main inlet channel 1282, and the multiple inlet branch channels 1284 located on the first side of the main inlet channel 1282 are staggered with the multiple inlet branch channels 1284 located on the second side of the main inlet channel 1282.
[0241] Figure 21 This is a planar schematic diagram of another micro-hole array chip provided in an embodiment of this disclosure. Figure 21 As shown, the microporous array substrate 110 includes a liquid inlet channel 128; the liquid inlet channel 128 includes multiple parallel main liquid inlet channels 1282 and n side liquid inlet channels 1284; each main liquid inlet channel 1282 has multiple side liquid inlet channels 1284 connected to it on both sides; the n side liquid inlet channels 1284 and n reaction chambers 120 are arranged in a one-to-one correspondence. Thus, the microporous array chip can introduce liquid (e.g., a sample to be tested) into the reaction chambers through the liquid inlet channels.
[0242] Figure 22 This is a planar schematic diagram of another micro-hole array chip provided in an embodiment of this disclosure. Figure 22 As shown, the microporous array substrate 110 includes a liquid inlet channel 128; the liquid inlet channel 128 includes multiple interconnected sub-liquid inlet channels 1285, each sub-liquid inlet channel 1285 being connected to multiple reaction chambers 120. The height of the sub-liquid inlet channel 1285 is greater than the height of the multiple reaction chambers 120 connected to it. Therefore, liquid can flow from the sub-liquid inlet channel into the reaction chamber by gravity. It should be noted that the aforementioned "height" refers to the distance between the bottom of the sub-liquid inlet channel or reaction chamber and the second main surface of the microporous array substrate.
[0243] In some examples, the heights of the multiple sub-inlet channels 1285 are different. Because the heights of the multiple sub-inlet channels are different, the microporous array chip can utilize gravity to allow liquid (e.g., the sample to be tested) to flow from the higher sub-inlet channels to the lower sub-inlet channels, thereby entering all reaction chambers. It should be noted that the "different heights of the multiple sub-inlet channels" mentioned above refers to the different distances between the bottom of the sub-inlet channels and the second main surface of the microporous array substrate.
[0244] In some examples, such as Figure 22 As shown, multiple sub-inlet channels 1285 are arranged sequentially, and the height of the multiple sub-inlet channels 1285 decreases sequentially along the arrangement direction of the multiple sub-inlet channels 1285. Of course, the embodiments of this disclosure include, but are not limited to, the height of the multiple inlet channels 1285 may also decrease sequentially from the middle to both sides.
[0245] Figure 23 This is a planar schematic diagram of another micro-hole array chip provided in an embodiment of this disclosure. Figure 23 As shown, the microporous array substrate 110 includes a liquid inlet channel 128; the shape of the orthographic projection of the liquid inlet channel 128 onto the first reference plane 201 on the first main surface 110A of the microporous array substrate 110 is a bent curve. Thus, the microporous array chip can directly introduce liquid (e.g., a sample to be tested) into the reaction chamber through the liquid inlet channel.
[0246] Figure 24 This is a cross-sectional schematic diagram of another micro-hole array chip provided in an embodiment of this disclosure. (See diagram below.) Figure 24 As shown, the microporous array chip 100 further includes a first substrate 310 and a second substrate 320. The first substrate 320 is located on one side of the microporous array substrate 110 and is spaced apart from the first main surface 110A of the microporous array substrate 110. The second substrate 320 is located on the side of the microporous array substrate 110 away from the first substrate 310. The second substrate 320 includes a heating electrode 325, the orthographic projection of the heating electrode 325 on the first reference plane 201 where the first main surface 110A of the microporous array substrate 110 is located overlaps with the orthographic projection of at least a portion of the n reaction chambers 120 on the first reference plane 201. Thus, the microporous array chip can heat at least a portion of the n reaction chambers through the heating electrode, thereby integrating the heating function into the microporous array chip.
[0247] In some examples, such as Figure 24 As shown, the orthographic projection of the heating electrode 325 onto the first reference plane 201 where the first main surface 110A of the microporous array substrate 110 is located overlaps with the orthographic projections of the n reaction chambers 120 onto the first reference plane 201. Therefore, the microporous array chip can simultaneously heat the n reaction chambers via the heating electrode.
[0248] In some examples, such as Figure 24 As shown, the first substrate 310 includes a first substrate 311 and a third hydrophobic layer 312; the third hydrophobic layer 312 is located on the side of the first substrate 311 near the second substrate 320. Thus, the third hydrophobic layer 312 has hydrophobic and oleophilic properties, thereby allowing liquids (e.g., the sample to be tested) to more easily enter the reaction chambers 120 defined by the microporous array substrate 110.
[0249] For example, the material of the third hydrophobic layer can be a resin or a silicon nitride, such as epoxy resin. The third hydrophobic layer can also be prepared using other suitable inorganic or organic materials, as long as the side of the third hydrophobic layer facing the second substrate is hydrophobic.
[0250] In some examples, such as Figure 24As shown, the first substrate 310 and the second substrate 310 can form an accommodating space 340 through sealant 330; the microporous array substrate 110 is disposed in the accommodating space 340; the first substrate 310 also includes at least one sample inlet 315, which penetrates the first substrate 311 and the third hydrophobic layer 312 and communicates with the accommodating space 340. Thus, the microporous array chip can introduce liquid into the microporous array substrate through the sample inlet.
[0251] In some examples, such as Figure 24 As shown, the first substrate 310 also includes at least one sample outlet 317, which penetrates the first substrate 311 and the third hydrophobic layer 312 and communicates with the accommodating space 340. Thus, the microporous array chip can discharge liquid through the sample outlet.
[0252] In some examples, such as Figure 24 As shown, the second substrate 320 further includes a second substrate 321, a control electrode 322, a first insulating layer 323, and a second insulating layer 324. The control electrode 322 is located on the second substrate 321. The first insulating layer 323 is located on the side of the control electrode 322 away from the second substrate 321. The first insulating layer 323 includes a connection hole 323H, which exposes at least a portion of the control electrode 322. The heating electrode 325 is located on the side of the first insulating layer 323 away from the second substrate 321 and is connected to the control electrode 322 through the connection hole 323H. The second insulating layer 324 is located on the side of the heating electrode 325 away from the first insulating layer 323, and the micro-hole array substrate 100 is located on the second insulating layer 324. Thus, the micro-hole array chip can apply a voltage to the heating electrode through the control electrode to drive the heating electrode to generate heat. On the other hand, since the second insulating layer is located on the side of the heating electrode away from the first insulating layer, the second insulating layer can be used to protect the heating electrode from water and oxygen corrosion, thereby improving the service life of the heating electrode. Furthermore, the second insulating layer also serves to provide insulation and planarization.
[0253] For example, the first insulating layer 323 and the second insulating layer 324 can be made of the same material or different materials. The materials of the first insulating layer 323 and the second insulating layer 324 can be inorganic insulating materials such as silicon oxide, silicon nitride, and silicon oxynitride, or organic insulating materials such as resin and polyimide.
[0254] In some examples, such as Figure 24As shown, the microporous array chip 100 also includes a photosensitive sensor 380; the photosensitive sensor 380 is located on the side of the second substrate 320 away from the first substrate 310, and is configured to detect light emitted from the reaction chamber 120 in the microporous array substrate 110. Thus, the microporous array chip can determine whether a reaction has occurred in the reaction chamber and the extent of the reaction through the photosensitive sensor; furthermore, by integrating the photosensitive sensor into the chip, the integration density is further improved.
[0255] Figure 25 This is a cross-sectional schematic diagram of another micro-hole array chip provided in an embodiment of this disclosure. (See diagram below.) Figure 25 As shown, the microvia array chip 100 further includes a first substrate 310 and a second substrate 320; the first substrate 320 is located on one side of the microvia array substrate 110 and is spaced apart from the first main surface 110A of the microvia array substrate 110. The microvia array chip 100 includes a plurality of microvia array substrates 110, arranged in a direction parallel to the first substrate 310 or the second substrate 320. Thus, the microvia array chip can achieve high-throughput detection by setting multiple microvia array chips. It should be noted that the planar layout structure of the multiple microvia array chips in this embodiment is not specifically limited. For example, the multiple microvia array substrates can form a matrix, or the multiple microvia array substrates can be arranged around a single microvia array substrate.
[0256] In some examples, such as Figure 25 As shown, when the microvia array chip includes multiple microvia array substrates 110, the second substrate 320 may include heating electrodes 325. The orthographic projection of the heating electrode 325 onto the first reference plane 201 where the first main surface 110A of the microvia array substrate 110 is located overlaps with the orthographic projection of at least a portion of the n reaction chambers 120 in at least one microvia array substrate 110 onto the first reference plane 201. Therefore, the microvia array chip can heat at least a portion of the n reaction chambers in at least one microvia array substrate through the heating electrode, thereby integrating the heating function into the microvia array chip. It should be noted that the microvia array chip may also be provided with multiple heating electrodes, with each heating electrode corresponding to one of the multiple microvia array substrates.
[0257] In some examples, such as Figure 25 As shown, the first substrate 310 includes a first substrate 311 and a third hydrophobic layer 312; the third hydrophobic layer 312 is located on the side of the first substrate 311 near the second substrate 320. Thus, the third hydrophobic layer 312 has hydrophobic and oleophilic properties, thereby allowing liquids (e.g., the sample to be tested) to more easily enter the reaction chambers 120 defined by the microporous array substrate 110.
[0258] For example, the material of the third hydrophobic layer can be a resin or a silicon nitride, such as epoxy resin. The third hydrophobic layer can also be prepared using other suitable inorganic or organic materials, as long as the side of the third hydrophobic layer facing the second substrate is hydrophobic.
[0259] In some examples, such as Figure 25 As shown, the first substrate 310 and the second substrate 310 can form an accommodating space 340 through sealant 330; the microporous array substrate 110 is disposed in the accommodating space 340; the first substrate 310 also includes at least one sample inlet 315, which penetrates the first substrate 311 and the third hydrophobic layer 312 and communicates with the accommodating space 340. Thus, the microporous array chip can introduce liquid into multiple microporous array substrates through the sample inlet.
[0260] In some examples, such as Figure 25 As shown, the first substrate 310 also includes at least one sample outlet 317, which penetrates the first substrate 311 and the third hydrophobic layer 312 and communicates with the accommodating space 340. Thus, the microporous array chip can discharge liquid through the sample outlet.
[0261] In some examples, such as Figure 25 As shown, the second substrate 320 further includes a second substrate 321, a control electrode 322, a first insulating layer 323, and a second insulating layer 324. The control electrode 322 is located on the second substrate 321. The first insulating layer 323 is located on the side of the control electrode 322 away from the second substrate 321. The first insulating layer 323 includes a connection hole 323H, which exposes at least a portion of the control electrode 322. The heating electrode 325 is located on the side of the first insulating layer 323 away from the second substrate 321 and is connected to the control electrode 322 through the connection hole 323H. The second insulating layer 324 is located on the side of the heating electrode 325 away from the first insulating layer 323, and the micro-hole array substrate 100 is located on the second insulating layer 324. Thus, the micro-hole array chip can apply a voltage to the heating electrode through the control electrode to drive the heating electrode to generate heat. On the other hand, since the second insulating layer is located on the side of the heating electrode away from the first insulating layer, the second insulating layer can be used to protect the heating electrode from water and oxygen corrosion, thereby improving the service life of the heating electrode. Furthermore, the second insulating layer also serves to provide insulation and planarization.
[0262] For example, the first insulating layer 323 and the second insulating layer 324 can be made of the same material or different materials. The materials of the first insulating layer 323 and the second insulating layer 324 can be inorganic insulating materials such as silicon oxide, silicon nitride, and silicon oxynitride, or organic insulating materials such as resin and polyimide.
[0263] In some examples, such as Figure 25 As shown, the microporous array chip 100 also includes a photosensitive sensor 380; the photosensitive sensor 380 is located on the side of the second substrate 320 away from the first substrate 310, and is configured to detect light emitted from the reaction chamber 120 in the microporous array substrate 110. Thus, the microporous array chip can determine whether a reaction has occurred in the reaction chamber and the extent of the reaction through the photosensitive sensor; furthermore, by integrating the photosensitive sensor into the chip, the integration density is further improved.
[0264] It is worth noting that, Figure 25 The illustrated microporous array chip achieves high-throughput detection by arranging multiple microporous array substrates in a direction parallel to the first substrate or the second substrate. However, embodiments of this disclosure include, but are not limited to, the microporous array chip can also achieve high-throughput detection by arranging multiple microporous array substrates in a direction perpendicular to the first substrate or the second substrate.
[0265] Figure 26 This is a cross-sectional schematic diagram of another micro-hole array chip provided in an embodiment of this disclosure. (See diagram below.) Figure 26 As shown, the microporous array chip 100 includes a microporous array substrate 110; the microporous array substrate 110 includes a first main surface 110A and a second main surface 110B disposed opposite to each other, n reaction chambers 120 and an idle area 130; the n reaction chambers 120 are arrayed in the microporous array substrate 110, and each reaction chamber 120 is configured to contain a sample to be tested. The microporous array chip 100 also includes an electro-hydrophilicity alteration layer 190 disposed on the inner surface 126 of the reaction chambers 120; the electro-hydrophilicity alteration layer 190 is connected to an external circuit through a conductive structure (e.g., a wire), so that the hydrophilicity can be changed by applying electricity (e.g., reducing hydrophilicity or changing from hydrophilic to hydrophobic), thereby automatically draining the liquid in the reaction chambers 120.
[0266] In some examples, the microporous array substrate in this microporous array chip can be made of anti-biological materials, thus enabling reuse.
[0267] In some examples, the micropore array substrate in the micropore array chip can be made of a material that bypasses the fluorescence excitation band, thereby preventing interference with fluorescence detection and improving detection accuracy.
[0268] It should be noted that the above... Figures 1-26 The total volume V of the n reaction chambers 120 in the microporous array chip shown can all satisfy the following formula to efficiently utilize the area of the microporous array substrate, thereby increasing the volume of a single reaction chamber, which in turn can improve the sensitivity of the microporous array chip and reduce the detection limit of the microporous array chip.
[0269]
[0270] Where (1-α) is the confidence level, S chip Let be the area of the microporous array substrate 110, h be the depth of the reaction chamber 120 in the direction perpendicular to the first reference plane 201, N be a positive integer greater than or equal to 3, and X be half the size of the spacing between adjacent reaction chambers 120. It should be noted that when N is infinitely large, the above-mentioned regular N-gon can be a circle.
[0271] At least one embodiment of this disclosure also provides a detection device. Figure 27 This is a schematic diagram of a detection device provided according to an embodiment of the present disclosure. Figure 27 As shown, the detection device 500 includes a microporous array chip 100 provided in any of the above examples. Since the microporous array chip can efficiently utilize the area of the microporous array substrate, thereby increasing the volume of a single reaction chamber, the sensitivity of the microporous array chip can be improved, and the detection limit of the microporous array chip can be reduced. Therefore, the detection device including the microporous array chip also has high sensitivity and a low detection limit.
[0272] Figure 28 This is a schematic diagram of another detection device provided in one embodiment of the present disclosure. Figure 28 As shown, the detection device 500 further includes a first housing 510 and a second housing 520; the first housing 510 is located on one side of the microporous array chip 100 and is spaced apart from the first main surface 110A; the second housing 520 is located on the side of the microporous array chip 100 away from the first housing 510 and is spaced apart from the second main surface 110B. The distance between the second main surface 110B and the second housing 520 is greater than or equal to the thickness of the microporous array chip 100. Therefore, this detection device facilitates the entry of liquid into the microporous array chip.
[0273] Figure 29 This is a plan view of a second housing in a detection device according to an embodiment of this disclosure. Figure 28 As shown, the second housing 520 includes a support structure 525, which includes a first platform portion 525A and a second platform portion 525B. The height of the second platform portion 525B is greater than the height of the first platform portion 525A. The first platform portion 525A is configured to contact the bottom surface of the micro-hole array chip 100, and the second platform portion 525B is configured to contact the side surface of the micro-hole array chip 100. Therefore, the detection device can support the micro-hole array chip through the first platform portion and position the micro-hole array chip through the second platform portion, thereby improving detection accuracy.
[0274] In some examples, such as Figure 29As shown, the shape of the orthographic projection of the first platform portion 525A onto the first reference plane 201 where the first main surface 110A is located includes an arc-shaped triangle. The shape of the second platform portion 525B onto the first reference plane 201 where the first main surface 110A is located (the first reference plane can be seen in...) Figure 27 The shape of the orthographic projection on the plane includes a semicircle, an arc triangle connected to the semicircle with a straight base, and the other two sides of the arc triangle are arcs.
[0275] In some examples, such as Figure 29 As shown, the second housing 520 also includes a positioning frustum 528, which is configured to contact the side of the micro-hole array chip 100, thereby further positioning the micro-hole array chip to improve detection accuracy.
[0276] At least one embodiment of this disclosure also provides a method of using a micro-hole array chip. The micro-hole array chip includes a micro-hole array substrate; the method of use includes the following steps S101-S103.
[0277] Step S101: Introduce the sample to be tested into the microporous array substrate; and
[0278] Step S102: The sample to be tested is encapsulated in a microporous array substrate. The microporous array substrate includes a first main surface and a second main surface arranged opposite to each other. The microporous array substrate includes n reaction chambers and an idle area. The n reaction chambers are arrayed in the microporous array substrate and configured to accommodate the sample to be tested. The orthographic projection of the reaction chambers onto the first reference plane where the first main surface is located is a regular N-gon. The idle area is arranged around the n reaction chambers. The area of the idle area is divided into n' virtual units. The shape of the orthographic projection of the virtual units onto the first reference plane is the same as the shape of the orthographic projection of the reaction chambers onto the first reference plane. The total volume V of the n reaction chambers satisfies the following formula:
[0279]
[0280] Where (1-α) is the confidence level, S chip denoted as the area of the micro-hole array substrate, h as the depth of the reaction chamber in the direction perpendicular to the first reference plane, N as a positive integer greater than or equal to 3, and X as half the dimension of the spacing between adjacent reaction chambers on the line connecting the centers of the adjacent reaction chambers.
[0281] In the method of using the microporous array chip provided in the embodiments of this disclosure, since the total volume V of the n reaction chambers satisfies the above formula, the method can efficiently utilize the area of the microporous array substrate, thereby increasing the volume of a single reaction chamber when the number of reaction chambers is sufficient, thereby improving the sensitivity of the microporous array chip and reducing the detection limit of the microporous array chip.
[0282] In some examples, the total volume V of the n reaction chambers satisfies the following formula:
[0283]
[0284] Therefore, this micro-hole array chip can efficiently utilize the area of the micro-hole array substrate, improve the sensitivity of the micro-hole array chip, and reduce the detection limit of the micro-hole array chip.
[0285] In some examples, the micropore array chip also includes a support region configured to house a support structure. In this case, the total volume V of the n reaction chambers satisfies the following formula:
[0286]
[0287] Among them, S support The area of the supporting region.
[0288] In the method of using the microporous array chip provided in this example, the support area can be used to contact the support structure (e.g., the support structure of the base), so that there is a certain gap between the microporous array substrate and the base, which facilitates the entry of the sample to be tested, thereby allowing the microporous array substrate to be oil-sealed.
[0289] In some examples, the shape of the orthographic projection of the reaction chamber onto the first reference plane where the first main surface is located and the shape of the orthographic projection of the virtual unit onto the first reference plane are both regular hexagons, and the total volume V of the n reaction chambers satisfies the following formula:
[0290]
[0291] Where X ranges from 10 to 20 micrometers, and h ranges from 190 to 320 micrometers.
[0292] In the microporous array chip provided in this example, the shape of the orthographic projection of each reaction chamber on the first reference plane is a regular hexagon. Since the total volume V of the n reaction chambers satisfies the above formula, the microporous array chip can efficiently utilize the area of the microporous array substrate, thereby increasing the volume of a single reaction chamber, which in turn can improve the sensitivity of the microporous array chip and reduce the detection limit of the microporous array chip.
[0293] In some examples, the spacing between adjacent reaction chambers along the center line connecting the centers of the adjacent reaction chambers can range from 20 to 40 micrometers, for example, 24 micrometers, 26 micrometers, 28 micrometers, 30 micrometers, 32 micrometers, 34 micrometers, or 36 micrometers.
[0294] In some examples, the depth of the reaction chamber in the direction perpendicular to the first reference plane may be 200 micrometers, 220 micrometers, 240 micrometers, 260 micrometers, 280 micrometers, or 300 micrometers.
[0295] In some examples, the number of reaction chambers on a single microporous array substrate can be 8,000-100,000. This results in higher detection accuracy for the microporous array chip.
[0296] In some examples, the number of reaction chambers on a micropore array substrate can be 8,000, 10,000, 20,000, 40,000, 60,000, 80,000, or 100,000.
[0297] In some examples, encapsulating the sample to be tested within a microporous array substrate includes: after introducing the sample into the microporous array substrate, attaching a first encapsulation film to the side of the first main surface away from the second main surface using electrostatics or an adhesive, and attaching a second encapsulation film to the side of the second main surface away from the first main surface. Thus, the microporous array chip can be easily and efficiently encapsulated within the microporous array substrate.
[0298] In some examples, encapsulating the sample to be tested within a microporous array substrate includes: after introducing the sample into the microporous array substrate, applying a photocurable grease to the opening of the reaction chamber near the first main surface; and curing the photocurable grease using ultraviolet light. Thus, the microporous array chip can utilize photocurable grease and photocuring processes to encapsulate the microporous array substrate, offering advantages such as simplicity, efficiency, and good encapsulation results.
[0299] In some examples, when the micro-hole array substrate employs, for example... Figure 19 When using the flexible substrate shown, the microporous array substrate may include a first sub-flexible microporous array substrate and a second sub-flexible microporous array substrate, and multiple sample flow channels are included between the first sub-flexible microporous array substrate and the second sub-flexible microporous array substrate. Passing a sample to be tested into the microporous array substrate includes passing the sample to be tested into the multiple sample flow channels.
[0300] For example, vacuum adsorption, pumping, or other methods can be used to introduce the sample into multiple sample channels.
[0301] In some examples, encapsulating the sample to be tested within a microporous array substrate includes using rollers to separate the sample channels to form multiple reaction chambers and then sealing the multiple reaction chambers. For example, the rollers have a heating function, and the first and second flexible microporous array substrates are joined together by heating at regular intervals, thereby separating the sample channels to form multiple reaction chambers.
[0302] The following points need to be explained:
[0303] (1) The accompanying drawings of the embodiments of this disclosure only involve the structures involved in the embodiments of this disclosure. Other structures can be referred to the general design.
[0304] (2) Where there is no conflict, features of the same embodiment and different embodiments of this disclosure can be combined with each other.
[0305] The above are merely specific embodiments of this disclosure, but the scope of protection of this disclosure is not limited thereto. Any variations or substitutions that can be easily conceived by those skilled in the art within the scope of the technology disclosed in this disclosure should be included within the scope of protection of this disclosure. Therefore, the scope of protection of this disclosure should be determined by the scope of the claims.
Claims
1. A micro-hole array chip, comprising: A microporous array substrate includes a first main surface and a second main surface disposed opposite to each other; n reaction chambers are arrayed in the microporous array substrate and configured to accommodate the sample to be tested. The shape of the orthographic projection of the reaction chambers onto the first reference plane where the first main surface is located is a regular N-gon. as well as An unused area is provided around the n reaction chambers; The area of the idle region is divided into n' virtual units. The shape of the orthographic projection of the virtual unit onto the first reference plane is the same as the shape of the orthographic projection of the reaction chamber onto the first reference plane. The total volume V of the n reaction chambers satisfies the following formula: , Where (1-α) is the confidence level, S chip Let h be the area of the microporous array substrate, h be the depth of the reaction chamber in the direction perpendicular to the first reference plane, N be a positive integer greater than or equal to 3, and X be half the dimension of the line connecting the centers of adjacent reaction chambers.
2. The micro-hole array chip according to claim 1, further comprising: The support area is configured to house the support structure. The total volume V of the n reaction chambers satisfies the following formula: , Among them, S support The area of the supporting region.
3. The micropore array chip according to claim 2, further comprising: The reaction zone is located around the periphery of the support zone. The n reaction chambers are located in the reaction region.
4. The micro-hole array chip according to claim 3, wherein, In the reaction region, the center distance between the orthographic projections of two adjacent reaction chambers onto the first reference plane is equal.
5. The micro-hole array chip according to any one of claims 1-4, wherein, The shape of the orthographic projection of the reaction chamber onto the first reference plane where the first main surface is located is a regular hexagon, and the total volume V of the n reaction chambers satisfies the following formula: , Where X ranges from 10 to 20 micrometers, and h ranges from 190 to 320 micrometers.
6. The micro-hole array chip according to any one of claims 1-4, wherein, The value of n ranges from 8000 to 100000.
7. The micro-hole array chip according to any one of claims 1-4, wherein, The total volume V of the n reaction chambers satisfies the following formula: 。 8. The micro-hole array chip according to any one of claims 1-4, further comprising: The first hydrophobic layer is located on the first main surface. The orthographic projection of the first hydrophobic layer onto the first reference plane is spaced apart from the orthographic projection of the reaction chamber onto the first reference plane.
9. The micro-hole array chip according to claim 8, wherein, The orthographic projection of the first hydrophobic layer onto the first reference plane includes a first opening, the edge of which is spaced apart from the edge of the reaction chamber onto the first reference plane.
10. The micro-hole array chip according to claim 8, further comprising: The second hydrophobic layer is located on the second main surface. The second hydrophobic layer extends to the edge of the reaction chamber.
11. The micropore array chip according to claim 10, wherein, The orthographic projection of the second hydrophobic layer onto the second reference plane where the second main surface is located includes a second opening, the edge of which coincides with the edge of the reaction chamber on the second reference plane.
12. The micropore array chip according to claim 8, further comprising: The second hydrophobic layer is located on the second main surface. The reaction chamber extends through the microporous array substrate in a direction perpendicular to the first reference plane, the second hydrophobic layer spans the reaction chamber, and the orthographic projection of the reaction chamber onto the second reference plane where the second main surface is located falls within the orthographic projection of the second hydrophobic layer onto the second reference plane.
13. The micro-hole array chip according to any one of claims 1-4, wherein, The reaction chamber is recessed from the first main surface into the microporous array substrate and has a cavity bottom located within the microporous array substrate. The distance between the cavity bottom and the first reference plane is less than the thickness of the microporous array substrate.
14. The micropore array chip according to claim 8, wherein, The reaction chamber is recessed from the first main surface into the microporous array substrate and has a cavity bottom located within the microporous array substrate. The distance between the cavity bottom and the first reference plane is less than the thickness of the microporous array substrate.
15. The micropore array chip according to claim 14, wherein, The contact angle between the first hydrophobic layer and the sample to be tested is less than the critical angle of the reaction chamber, whereby the critical angle is the angle between the extension of the sidewall of the reaction chamber and the tangent of the surface of the sample to be tested that contacts the sidewall of the reaction chamber.
16. The micro-hole array chip according to claim 14, wherein, The bottom of the cavity includes at least one vent hole, and each vent hole penetrates the bottom of the cavity in a direction perpendicular to the first reference plane.
17. The micro-hole array chip according to claim 16, wherein, The bottom of the cavity includes an exhaust port, and the orthographic projection of the exhaust port on the second reference plane where the second main surface is located is located at the center of the orthographic projection of the bottom of the cavity on the second reference plane.
18. The micro-hole array chip according to claim 16, wherein, The bottom of the cavity includes a plurality of exhaust holes, and the orthographic projection of the exhaust holes on the second reference plane where the second main surface is located is arranged around the center of the orthographic projection of the bottom of the cavity on the second reference plane.
19. The micro-hole array chip according to claim 8, further comprising: dialysis membrane; as well as Second hydrophobic layer, The reaction chamber extends through the microporous array substrate in a direction perpendicular to the first reference plane, the second hydrophobic layer extends to the edge of the reaction chamber, and the dialysis membrane spans the reaction chamber.
20. The micro-hole array chip according to claim 19, wherein, The orthographic projection of the reaction chamber onto the second reference plane where the second main surface is located falls within the orthographic projection of the dialysis membrane onto the second reference plane.
21. The micropore array chip according to claim 19, wherein, The dialysis membrane is a flexible dialysis membrane.
22. The micropore array chip according to claim 19, wherein, The dialysis membrane is located on the side of the second hydrophobic layer near the second main surface.
23. The micropore array chip according to claim 19, wherein, The dialysis membrane is located on the side of the second hydrophobic layer away from the second main surface.
24. The micro-hole array chip according to any one of claims 1-4, wherein, The angle between the inner surface of the reaction chamber and the first main surface is greater than 90 degrees.
25. The micro-hole array chip according to any one of claims 1-4, wherein, The inner surface of the reaction chamber includes a first sub-surface and a second sub-surface in a direction perpendicular to the first reference plane, wherein the second sub-surface is located on the side of the first sub-surface away from the first main surface. The angle between the first sub-surface and the first main surface is greater than 90 degrees, and the angle between the second sub-surface and the second main surface is greater than 90 degrees.
26. The micro-hole array chip according to any one of claims 1-4, wherein, The inner surface of the reaction chamber includes a first sub-surface, a second sub-surface, and a third sub-surface in a direction perpendicular to the first reference plane. The second sub-surface is located on the side of the first sub-surface away from the first main surface, and the third sub-surface is located on the side of the second sub-surface away from the first sub-surface. The angle between the first sub-surface and the first main surface is greater than 90 degrees, the plane containing the second sub-surface is perpendicular to the first reference plane, and the angle between the third sub-surface and the second main surface is greater than 90 degrees.
27. The micro-hole array chip according to any one of claims 1-4, wherein, The inner surface of the reaction chamber includes a first sub-surface, a second sub-surface, and a third sub-surface in a direction perpendicular to the first reference plane. The second sub-surface is located on the side of the first sub-surface away from the first main surface, and the third sub-surface is located on the side of the second sub-surface away from the first sub-surface. The angle between the first sub-surface and the first main surface is greater than 90 degrees, the second sub-surface is an arc surface and is recessed into the micro-hole array substrate, and the angle between the third sub-surface and the second main surface is greater than 90 degrees.
28. The micro-hole array chip according to any one of claims 1-4, wherein, A first hydrophilic membrane and a second hydrophilic membrane are disposed on the inner surface of the reaction chamber. The first hydrophilic membrane and the second hydrophilic membrane are disposed adjacent to each other in a direction perpendicular to the first reference plane. The surface of the first hydrophilic membrane away from the inner surface of the reaction chamber is an arc surface protruding towards the central axis of the reaction chamber. The surface of the second hydrophilic membrane away from the inner surface of the reaction chamber is an arc surface protruding towards the central axis of the reaction chamber.
29. The micropore array chip according to claim 28, wherein, The inner surface of the reaction chamber is a plane. The thickness of the first hydrophilic membrane varies in the direction perpendicular to the inner surface, so that the surface of the first hydrophilic membrane away from the inner surface of the reaction chamber is an arc surface. The thickness of the second hydrophilic membrane varies in the direction perpendicular to the inner surface, so that the surface of the second hydrophilic membrane away from the inner surface of the reaction chamber is an arc surface.
30. The micropore array chip according to claim 28, wherein, The inner surface of the reaction chamber includes a first sub-surface and a second sub-surface in a direction perpendicular to the first reference plane, wherein the second sub-surface is located on the side of the first sub-surface away from the first main surface. The first sub-surface protrudes toward the central axis of the reaction chamber, such that the surface of the first hydrophilic membrane away from the inner surface of the reaction chamber is an arc surface. The second sub-surface protrudes toward the central axis of the reaction chamber, such that the surface of the second hydrophilic membrane away from the inner surface of the reaction chamber is an arc surface.
31. The micro-hole array chip according to any one of claims 1-4, wherein, The shape of the orthographic projection of the reaction chamber onto the first reference plane is virtually one of a regular hexagon or a regular octagon.
32. The micro-hole array chip according to any one of claims 1-4, wherein, The shape of the orthographic projection of the reaction chamber onto the first reference plane is virtually a triangle.
33. The micro-hole array chip according to any one of claims 1-4, further comprising: The first encapsulation film is located on the side of the first main surface away from the second main surface; The second encapsulation film is located on the side of the second main surface away from the first main surface. The first encapsulation film and the second encapsulation film are attached to the microporous array substrate by electrostatic or adhesive bonding.
34. The micropore array chip according to claim 8, further comprising: The UV-curing oil is located at the opening of the reaction chamber near the first main surface. The photocurable oil includes a boss structure, which is in contact with the first main surface and located on the side of the first hydrophobic layer near the central axis of the reaction chamber.
35. The micro-hole array chip according to any one of claims 1-4, wherein, The microporous array substrate is a flexible substrate.
36. The micro-hole array chip according to any one of claims 1-4, wherein, The microporous array substrate further includes: Inlet channel The n reaction chambers are connected to the liquid inlet channel, and a one-way membrane is provided between each reaction chamber and the liquid inlet channel.
37. The micropore array chip according to claim 36, wherein, The liquid inlet channel includes: Main inlet channel; There are n inlet branch channels, each connected to the main inlet channel. The n liquid inlet branch channels and the n reaction chambers are arranged in a one-to-one correspondence.
38. The micro-hole array chip according to any one of claims 1-4, wherein, The microporous array substrate further includes: The liquid inlet channel includes multiple interconnected sub-liquid inlet channels. Each sub-inlet channel is connected to multiple reaction chambers, and the height of each sub-inlet channel is greater than the height of the corresponding multiple reaction chambers.
39. The micro-hole array chip according to claim 38, wherein, The heights of the multiple sub-inlet channels decrease sequentially.
40. The micro-hole array chip according to claim 38, wherein, The height of the multiple liquid inlet channels decreases sequentially from the middle to both sides.
41. The micro-hole array chip according to any one of claims 1-4, further comprising: The first substrate is located on one side of the microporous array substrate and is spaced apart from the first main surface; as well as The second substrate is located on the side of the microporous array substrate away from the first substrate. The second substrate includes a heating electrode, the orthographic projection of which overlaps with the orthographic projection of at least a portion of the n reaction chambers onto the first reference plane.
42. The micro-hole array chip according to claim 41, wherein, The first substrate includes: First substrate; The third hydrophobic layer is located on the side of the first substrate closer to the second substrate.
43. The micro-hole array chip according to claim 41, wherein, The second substrate further includes: Second substrate; The control electrode is located on the second substrate. A first insulating layer is located on the side of the control electrode away from the second substrate; and Second insulating layer, The first insulating layer includes a connection hole that exposes at least a portion of the control electrode. The heating electrode is located on the side of the first insulating layer away from the second substrate and is connected to the control electrode through the connection hole. The second insulating layer is located on the side of the heating electrode away from the first insulating layer, and the micro-hole array substrate is located on the second insulating layer.
44. The micro-hole array chip according to claim 41, further comprising: A photosensitive sensor is located on the side of the second substrate away from the first substrate. The photosensitive sensor is configured to detect light emitted from the reaction chamber in the microporous array substrate.
45. A detection device comprising a microporous array chip according to any one of claims 1-44.
46. The detection device according to claim 45, further comprising: The first outer shell is located on one side of the micro-hole array chip and is spaced apart from the micro-hole array chip; as well as The second outer shell is located on the side of the micro-hole array chip away from the first outer shell and is spaced apart from the micro-hole array chip. The distance between the micro-hole array chip and the second outer shell is greater than or equal to the thickness of the micro-hole array chip.
47. The detection device according to claim 46, wherein, The second housing includes a support structure, which includes a first platform portion and a second platform portion. The height of the second platform portion is greater than the height of the first platform portion. The first platform portion is configured to contact the bottom surface of the micro-hole array chip, and the second platform portion is configured to contact the side surface of the micro-hole array chip.
48. The detection device according to claim 47, wherein, The shape of the orthographic projection of the first platform portion onto the first main surface includes an arc triangle, and the shape of the orthographic projection of the second platform portion onto the first main surface includes a semicircle. The base of the arc triangle connected to the semicircle is a straight line, and the other two sides of the arc triangle are arcs.
49. The detection device according to claim 47, wherein, The second housing also includes a positioning frustum configured to contact the side of the micro-hole array chip.
50. A method of using a micro-hole array chip, wherein, The microporous array chip includes a microporous array substrate, and the method of using it includes: The sample to be tested is introduced into the microporous array substrate; The sample to be tested is encapsulated in the microporous array substrate. The microporous array substrate includes a first main surface and a second main surface disposed opposite to each other. The microporous array substrate includes n reaction chambers and an idle region. The n reaction chambers are arrayed within the microporous array substrate and configured to accommodate the sample to be tested. The orthographic projection of each reaction chamber onto a first reference plane containing the first main surface is a regular N-gon. The idle region surrounds the n reaction chambers. The area of the idle region is divided into n' virtual units. The orthographic projection of each virtual unit onto the first reference plane has the same shape as the orthographic projection of the reaction chamber onto the first reference plane. The total volume V of the n reaction chambers satisfies the following formula: , Where (1-α) is the confidence level, S chip Let h be the area of the microporous array substrate, h be the depth of the reaction chamber in the direction perpendicular to the first reference plane, N be a positive integer greater than or equal to 3, and X be half the dimension of the line connecting the centers of adjacent reaction chambers.
51. The method of using the micro-hole array chip according to claim 50, wherein, Encapsulating the sample to be tested within the microporous array substrate includes: After the sample to be tested is introduced into the microporous array substrate, the first encapsulation film is attached to the side of the first main surface away from the second main surface by electrostatic or colloid method, and the second encapsulation film is attached to the side of the second main surface away from the first main surface.
52. The method of using the micro-hole array chip according to claim 50, wherein, Encapsulating the sample to be tested within the microporous array substrate includes: After the sample to be tested is introduced into the microporous array substrate, a photocurable oil is applied to the opening of the reaction chamber near the first main surface; and The UV-curable oil is cured using ultraviolet light.
53. The method of using the micro-hole array chip according to any one of claims 50-52, wherein, The microporous array substrate includes a first flexible microporous array substrate and a second flexible microporous array substrate, with multiple sample flow channels between the first and second flexible microporous array substrates. The sample to be tested is introduced into the microporous array substrate, including: The sample to be tested is introduced into the multiple sample channels.
54. The method of using the micro-hole array chip according to claim 53 further includes: The sample to be tested is introduced into the multiple sample channels using a vacuum method.
55. The method of using the micro-hole array chip according to claim 53, wherein, Encapsulating the sample to be tested within the microporous array substrate includes: using rollers to separate the sample channels to form multiple reaction chambers, and sealing the multiple reaction chambers.
Citation Information
Patent Citations
Microwell array articles and methods of use
CN102665916A
Arrays of discrete cell culture microenvironments, methods of making such arrays and uses thereof
CN105358675A