The present disclosure relates to the field of digital polymerase chain reaction (dPCR) chip technology, and in particular to a chip packaging structure and a chip packaging method.
The digital polymerase chain reaction (dPCR) is an absolute quantification technique for nucleic acid molecules. Compared with the previous generation qPCR (quantitative polymerase chain reaction), the dPCR can directly calculate the number of DNA molecules, give an absolute quantification of an initial sample, and has higher sensitivity and accuracy. The dPCR technique may be divided into two categories: droplet dPCR and micro-trap dPCR. Because it is difficult to maintain a conventional droplet generating device to stably generate uniform droplets for a long time, the micro-trap dPCR attracts more and more attentions, and the main principle of the micro-trap dPCR is to disperse nucleic acid solution into thousands or tens of thousands of micropores in a chip, count fluorescence signals of the micropores after a PCR cycle, and calculate the nucleic acid concentration of the original solution according to Poisson distribution.
However, blind holes are generally adopted as the micropores of the conventional micro-trap dPCR, and there are problems that the sample cannot fully fill the micropores, bubbles exist in the micropores, and the like after the sample enters into the micropores.
The present disclosure is directed to at least one of the technical problems in the prior art, and provides a chip packaging structure and a chip packaging method, which can solve the problems that the sample cannot fully fill micropores, bubbles exist in the micropores, and the like after the sample enters into the micropores.
To achieve the above object, the present disclosure provides a chip packaging structure, including: a sample substrate having a plurality of through holes therein penetrating through the sample substrate along a thickness direction of the sample substrate; a first cover plate and a second cover plate respectively on two opposite sides of the sample substrate along the thickness direction of the sample substrate and attached to the sample substrate; and at least one pair of a sample inlet and a sample outlet, each pair of the sample inlet and the sample outlet being in one of the first cover plate and the second cover plate or in the first cover plate and the second cover plate, respectively, a flow path existing between each pair of the sample inlet and the sample outlet, where a first flow channel structure is on a surface of the first cover plate opposite to the sample substrate, a second flow channel structure is on a surface of the second cover plate opposite to the sample substrate, and the first flow channel structure and the second flow channel structure are connected together with the plurality of through holes, to form a continuous channel corresponding to the flow path between each pair of the sample inlet and the sample outlet.
In some implementations, the first flow channel structure includes a plurality of first flow channels arranged at intervals; the second flow channel structure includes a plurality of second flow channels arranged at intervals; two through holes of the plurality of through holes on the same flow path are at a start point and an end point of the flow path, respectively, the through hole at the start point includes an end communicated with the sample inlet, and another end communicated with the through hole downstream and adjacent to the through hole at the start point through one first flow channel or one second flow channel; the through hole at the end point includes an end communicated with the sample outlet, and another end communicated with the through hole upstream and adjacent to the through hole at the end point through one first flow channel or one second flow channel; and both ends of each remaining through hole are communicated with two through holes upstream and downstream and adjacent to said each remaining through hole through one first flow channel and one second flow channel, respectively.
In some implementations, the flow path between the at least one pair of the sample inlet and the sample outlet includes a main path and a plurality of branch paths, where two through holes on each branch path are respectively at a start point and an end point of the branch path, and are shared by the main path; the remaining through holes on the branch path are not shared by the main path; and for each shared through hole, the first flow channel or the second flow channel communicated with the shared through hole is communicated with the through hole, adjacent to the shared through hole, upstream or downstream on the main path, and communicated with the through hole, adjacent to the shared through hole, upstream or downstream on the branch path where the shared through hole is located.
In some implementations, the plurality of through holes are arranged in a square array, and through holes at both ends of a first diagonal line of the square array are respectively communicated with one pair of the sample inlet and the sample outlet; and all the through holes on the first diagonal line are on the main path; and the plurality of branch paths are divided into a plurality of pairs, each pair of branch paths is symmetrically distributed on both sides of the first diagonal line, and two through holes at a start point and an end point of each pair of branch paths are shared by the main path, and through holes on a start point and an end point of each branch path are symmetrically distributed on both sides of a second diagonal line of the square array.
In some implementations, the plurality of through holes are arranged in a rectangular or square array, the through holes at a head end and a tail end of a first row or column of the rectangular or square array serve as a start point or an end point of the flow path, and are respectively communicated with one pair of the sample inlet and the sample outlet; and the flow path includes a plurality of sub-paths connected together end to end and in series, the number of the sub-paths is the same as the number of rows or columns of the rectangular or square array, and all the through holes on each row or column of the rectangular or square array are correspondingly on each sub-path.
In some implementations, the plurality of through holes are arranged in a rectangular or square array, the number of pairs of sample inlets and sample outlets is the same as the number of rows or columns of the rectangular or square array, and all the through holes in each row or each column of the rectangular or square array are correspondingly on the flow path between each pair of the sample inlet and the sample outlet.
In some implementations, each first flow channel is a first groove in the surface of the first cover plate opposite to the sample substrate, and each second flow channel is a second groove in the surface of the second cover plate opposite to the sample substrate, and an orthographic projection of an inner surface of each of the first groove and the second groove on a plane parallel to the thickness direction of the sample substrate is of an arc shape.
In some implementations, the arc shape is a shape obtained by taking an arc from a circle or an ellipse.
In some implementations, inner surfaces of a hole wall of each through hole, the first groove and the second groove are all surfaces subjected to hydrophilic treatment; a surface of the sample substrate except for the through holes is a surface subjected to hydrophobic treatment; a surface of the first cover plate except for the inner surface of the first groove is a surface subjected to hydrophobic treatment; and a surface of the second cover plate except for the inner surface of the second groove is a surface subjected to hydrophobic treatment.
In some implementations, the first cover plate and the second cover plate are made of polymethyl methacrylate or glass.
In some implementations, the second flow channel structure is on a surface of the first cover plate away from the sample substrate, and the first flow channel structure is on a surface of the second cover plate away from the sample substrate, so that the first cover plate and the second cover plate form two multi-role cover plates with identical structures; and the two multi-role cover plates are staggered in the thickness direction of the sample substrate, so that the sample inlet and the sample outlet in one multi-role cover plate of the two multi-role cover plates do not overlap with the other multi-role cover plate of the two multi-role cover plates.
In some implementations, the chip packaging structure includes at least three multi-role cover plates, at least one sample substrate is between every two adjacent multi-role cover plates, and sequentially attached together along a direction from the first cover plate to the second cover plate, and the at least three multi-role cover plates are sequentially staggered in the thickness direction of the at least one sample substrate, so that the sample inlet and the sample outlet in each multi-role cover plate do not overlap with the other multi-role cover plates.
In some implementations, the chip packaging structure includes a plurality of sample substrates sequentially attached to each other in a direction from the first cover plate to the second cover plate, each sample substrate includes a through hole region and a non-through hole region, and each through hole is in the through hole region; and every two adjacent sample substrates are slidable with respect to each other, so that the through holes in one of the two adjacent sample substrates are in the through hole region of the other sample substrate and coincide with the through holes in the other sample substrate; or, the through holes in one of the two adjacent sample substrates are in the non-through hole region of the other sample substrate and isolated from the through holes in the other sample substrate.
In some implementations, the through holes in each sample substrate are arranged in a rectangular or square array, a spacing region between every two adjacent rows of through holes and between every two adjacent columns of through holes in the rectangular or square array is the non-through hole region, and a width of the spacing region is greater than two times a diameter of each through hole.
In some implementations, the through holes in each sample substrate are arranged in a rectangular or square array, and a region of the sample substrate outside the rectangular or square array is the non-through hole region capable of accommodating the entire rectangular or square array.
In some implementations, in response to that the through holes in one of the two adjacent sample substrates are in the non-through hole region of the other sample substrate of the two adjacent sample substrates, arrays on all the sample substrates are arranged in an array.
In some implementations, the sample substrate includes a through hole region and a non-through hole region, the through holes are in the through hole region; and each of the first cover plate and the second cover plate is slidable with respect to the sample substrate, so that the first flow channel structure and the second flow channel structure are in the through hole region and are communicated with the through holes; or the first flow channel structure and the second flow channel structure are in the non-through hole region and are isolated from the through holes.
In some implementations, the plurality of through holes are arranged in a square array, and a spacing region between every two adjacent rows of through holes and between every two adjacent columns of through holes in the square array is the non-through hole region, and a width of the spacing region is greater than that of each of the first flow channel structure and the second flow channel structure.
The present disclosure further provides a chip packaging method, applied to the chip packaging structure provided in the present disclosure, including: injecting a sample from each sample inlet until the sample fully fills the continuous channel along the flow path and flows out from the sample outlet; peeling off one of the first cover plate and the second cover plate from the sample substrate; attaching a sealing cover plate to the surface of the sample substrate, to which one of the first cover plate and the second cover plate is previously attached, a sealing groove being provided in the sealing cover plate, and an orthographic projection of the sealing groove on a plane parallel to the sample substrate completely covers an orthographic projection of all the through holes on the plane parallel to the sample substrate, and an inlet and an outlet being provided in the sealing cover plate and communicated with the sealing groove; injecting a sealing medium into the sealing groove from the inlet until the sealing medium fully fills the sealing groove and flows out from the outlet; blocking the inlet and the outlet, and then turning over the chip packaging structure by 180°; peeling off the other of the first cover plate and the second cover plate from the sample substrate; attaching another sealing cover plate to the surface of the sample substrate, to which the other of the first cover plate and the second cover plate is previously attached; injecting a sealing medium into a sealing groove from an inlet of the another sealing cover plate until the sealing medium fully fills the sealing groove and flows out from an outlet; and blocking the inlet and the outlet of the another sealing cover plate.
In some implementations, the chip packaging structure includes a plurality of sample substrates sequentially attached to each other in a direction from the first cover plate to the second cover plate, each sample substrate includes a through hole region and a non-through hole region, and each through hole is located in the through hole region; and every two adjacent sample substrates are slidable with respect to each other, so that through holes in one of the two adjacent sample substrates are located in the through hole region of the other sample substrate and coincide with the through holes in the other sample substrate; or, the through holes in one of the two adjacent sample substrates are located in the non-through hole region of the other sample substrate and isolated from the through holes in the other sample substrate; and after blocking the inlet and the outlet of the another sealing cover plate, the chip packaging method further includes: keeping still a first sample substrate adjacent to the first cover plate or the second cover plate, and sequentially sliding the other sample substrates, until through holes in one of the two adjacent sample substrates are located in the non-through hole region of the other sample substrate and isolated from through holes in the other sample substrate.
The present disclosure further provides a chip packaging method, applied to the chip packaging structure provided in the present disclosure, including: enabling the first flow channel structure and the second flow channel structure to be located in the through hole region and to be communicated with the through holes; injecting a sample from each sample inlet until the sample fully fills the continuous channel along the flow path and flows out from the sample outlet; and sliding each of the first cover plate and the second cover plate with respect to the sample substrate, so that the first flow channel structure and the second flow channel structure are located in the non-through hole region.
To make objects, technical solutions and advantages of the present disclosure more apparent, the present disclosure will be described in further detail with reference to the accompanying drawings. It is apparent that the described embodiments are only some, not all, embodiments of the present disclosure. All other embodiments, which can be derived by a person skilled in the art from the embodiments disclosed herein without any creative effort, shall fall within the protection scope of the present disclosure.
The shapes and sizes of various elements shown in the drawings are not necessarily drawn to scale and are merely intended to facilitate an understanding of contents of the embodiments of the present disclosure.
Unless defined otherwise, technical or scientific terms used herein shall have the ordinary meaning as understood by one of ordinary skill in the art to which the present disclosure belongs. The terms “first”, “second”, and the like used in the present disclosure are not intended to indicate any order, quantity, or importance, but rather are used for distinguishing one element from another. Further, the term “a”, “an”, “the”, or the like used herein does not denote a limitation of quantity, but rather denotes the presence of at least one element. The term of “comprising”, “including”, or the like, means that the element or item preceding the term contains the element or item listed after the term and its equivalent, but does not exclude other elements or items. The term “connected”, “coupled”, or the like is not limited to physical or mechanical connections, but may include electrical connections, whether direct or indirect connections. The terms “upper/on/above”, “lower/below/under”, “left”, “right”, and the like are used only for indicating relative positional relationships, and in response to that an absolute position of an object being described is changed, the relative positional relationships may be changed accordingly.
The disclosed embodiments are not limited to the embodiments shown in the drawings, but include modifications of configurations formed based on a manufacturing process. Thus, areas illustrated in the drawings have schematic properties, and shapes of the areas shown in the drawings illustrate specific shapes of the areas of elements, but are not intended to be limiting.
As shown in
For each pair of the sample inlet 4 and the sample outlet, the continuous channel extends along the flow path between the sample inlet 4 and the sample outlet, so that the sample can enter the continuous channel through the sample inlet 4, then flow through the continuous channel along the flow path, and then flow out from the sample outlet; the continuous channel is composed of the first flow channel structure on the first cover plate 2, the second flow channel structure on the second cover plate 3, and the through holes in the flow path. Thus, the sample can fully fill all the through holes, and no bubble is to be generated because the through holes penetrate through the sample substrate 1, thereby solving the problems, in the prior art, that the sample cannot fully fill micropores, bubbles exist in the micropores, and the like after the sample enters into the micropores.
In some implementations, as shown in
In some implementations, in order to improve the hydrophobic property of the cover plate and thus, enable the cover plate to be peeled off more easily, materials of the first cover plate 2 and the second cover plate 3 include PMMA (polymethyl methacrylate) or glass. However, the embodiment is not limited to above. In practical applications, the materials of the first cover plate 2 and the second cover plate 3 may also be other materials that are easy to be peeled off.
In some implementations, the first cover plate 2 and the second cover plate 3 may be adhered to the sample substrate 1 by using glue, for example, a glue with a low viscidity, such as a pressure sensitive glue to be peeled off by a relatively low peel strength. Alternatively, the first cover plate 2 and the second cover plate 3 may be attached to the sample substrate 1 in another way for attaching plates in layers together, such as an attaching way through a pressure.
It should be noted that the first cover plate 2 and the second cover plate 3 may serve as packaging cover plates of the sample substrate 1, that is, the first cover plate 2, the second cover plate 3 and the sample substrate 1 together form a chip. In this case, after the sample being introduced for the sample substrate 1 by using the first cover plate 2 and the second cover plate 3, the first cover plate 2 and the second cover plate 3 are used for packaging, so that the sample in the sample substrate 1 is isolated from outside. A specific packaging manner may include: sliding the first cover plate 2 and the second cover plate 3 with respect to the sample substrate 1 (as described in detail below). Alternatively, the first cover plate 2 and the second cover plate 3 may be used for packaging in any other packaging manner. Alternatively, after the sample being introduced for the sample substrate 1 by using the first cover plate 2 and the second cover plate 3, the first cover plate 2 and the second cover plate 3 may be peeled off from the sample substrate 1, and then other packaging cover plates are attached to surfaces of the sample substrate 1, to which the first cover plate 2 and the second cover plate 3 are previously attached (which will be described in detail later), so that the sample in the sample substrate 1 is isolated from outside. In this case, the sample substrate 1 and the attached packaging cover plates form a chip, and the first cover plate 2 and the second cover plate 3 serve as a packaging structure for introducing the sample into the sample substrate 1 and are peeled off after the sample being introduced for the sample substrate 1. The chip is, for example, a digital polymerase chain reaction (dPCR) chip.
In some implementations, the sample substrate may be made of a transparent material such as a glass; and alternatively, may be made of silicon to facilitate a preparation of the sample substrate.
The first flow channel structure and the second flow channel structure each may have various structures. For example, as shown in
Specifically, in the embodiment, as shown in
In some implementations, each first flow channel 21 is a first groove formed in the surface of the first cover plate 2 opposite to the sample substrate 1, and each second flow channel 31 is a second groove formed in the surface of the second cover plate 3 opposite to the sample substrate 1, and an orthographic projection of an inner surface of each of the first groove and the second groove on a plane parallel to a thickness direction of the sample substrate 1 is of an arc shape. In this way, a corner of about 90° or less in the inner surface of the first groove or the second groove can be avoided, and the generation of bubbles can be further avoided. Specifically, for example, the arc shape is a shape obtained by taking an arc from a circle or an ellipse (i.e., an arc part of a circle or an ellipse).
In some implementations, a width of each of the first and second grooves is approximately the same as a diameter of each through hole 11, and a depth of each of the first and second grooves is, for example, about 10 μm. In addition, in some implementations, for example, an orthographic projection of each of the first groove and the second groove on a plane parallel to the sample substrate 1 is of a long circle shape, and orthographic projections of two circular arc parts at two ends of the long circle shape on the plane parallel to the sample substrate 1 respectively coincide with orthographic projections of two through holes 11 communicated with the long circle shape on the plane parallel to the sample substrate 1.
It should be noted that, in the embodiment, the first flow channel 21 and the second flow channel 31 each are used for communicating two adjacent through holes together, but the embodiment is not limited thereto. In practical applications, alternatively, the first flow channel 21 and the second flow channel 31 each may be used for communicating together three adjacent through holes, four adjacent through holes, or five adjacent through holes or more according to different arrangements of the through holes, different communication paths, or the like, which is not particularly limited by the present disclosure.
In some implementations, in order to ensure that the sample can smoothly enter the through holes 11 and reduce the sample adsorbed by the surfaces of the cover plates except for the grooves, inner surfaces of first groove and second groove are surfaces subjected to hydrophilic treatment, and surfaces of the first cover plate 2 except for the inner surfaces of the first grooves are surfaces subjected to hydrophobic treatment; surfaces of the second cover plate 3 except for the inner surfaces of the second grooves are surfaces subjected to hydrophobic treatment. The hydrophilic treatment includes various methods. For example, the first cover plate 2 and the second cover plate 3 may be immersed and washed in acid solution or alkali solution, and be subjected to plasma treatment, coated with a surfactant, coated with a hydrophilic silane modification agent, or the like. The hydrophobic treatment includes various methods. For example, a silicon nitride film layer, a polytetrafluoroethylene film layer are formed on the surfaces of the first cover plate 2 and the second cover plate 3 except for the grooves, and a hydrophobic silane modification agent or the like is coated on the surfaces. In addition, a hole wall of each through hole 11 in the sample substrate 1 may also be a surface subjected to the hydrophilic treatment, and the surface of the sample substrate 1 except for the through holes 11 may be a surface subjected to the hydrophobic treatment.
The communication path between each pair of the sample inlet and the sample outlet may be various. For example, as shown in
The structure and the arrangement of the first flow channels 21 of the first cover plate 2 and the second flow channels 31 of the second cover plate 3 are shown in
It should be noted that, in practical applications, the sub-paths may be adjusted, with a head end through hole and a tail end through hole in one of the last column (the rightmost column in the vertical direction in
It should be noted that, in the embodiment, the sample inlet 4 and the sample outlet 5 are in one pair, and the flow path between the sample inlet 4 and the sample outlet 5 is formed by a main path, but the embodiment is not limited thereto. In practical applications, alternatively, a plurality of pairs of sample inlets 4 and sample outlets 5 may be included, and each pair of the sample inlet 4 and the sample outlet 5 corresponds to a flow path, and certainly, the flow path may be formed by at least one main path between the sample inlet 4 and the sample outlet 5, or may be formed by a combination of at least one main path and at least one branch path, which is not particularly limited in the present disclosure. In addition, the sample inlets 4 and the sample outlets 5 may not be provided in pairs, that is, one group of sample inlets 4 may correspond to one sample outlet 5, or one sample inlet may correspond to one group of sample outlets 5, or one group of sample inlets 4 may correspond to one group of sample inlets 5, each group of sample inlets 4 includes multiple sample inlets 4 and each group of sample outlets 5 includes multiple sample outlets 5. However, no matter the group (of sample inlets or sample outlets) corresponds to the individual (the sample outlet or the sample inlet), or the group (of sample inlets or sample outlets) corresponds to the group (of sample outlets or sample inlets), the design of the corresponding flow path between the two is similar to that of the flow path between the one pair of the sample inlet 4 and the sample outlet 5 as described above.
It should be noted that, in the embodiment, the sample inlet 4 and the sample outlet 5 are both located in the first cover plate 2. However, the embodiment is not limited thereto. In practical applications, the sample inlet 4 and the sample outlet 5 may also be both located in the second cover plate 3, or located in the first cover plate 2 and the second cover plate 3, respectively. In other words, each of the sample inlet 4 and the sample outlet 5 may face upward or downward.
Compared with the first embodiment, the chip packaging structure provided in this embodiment also includes the sample substrate 1, the first cover plate 2 and the second cover plate 3, and the at least one pair of the sample inlet 4 and the sample outlet 5. The structures and functions of these components are the same as those in the first embodiment, but the difference between the first embodiment and the second embodiment is in the flow path.
Specifically, in order to increase the speed that the sample is introduced, the flow path between the at least one pair of the sample inlet 4 and the sample outlet 5 includes a main path and a plurality of branch paths, two through holes of the through holes on each branch path are respectively located at a start point and an end point of the branch path, and are shared by the main path (the two through holes on the branch path are common to any two through holes on the main path); the remaining through holes on the branch path are not shared by the main path. That is, the start point of each branch path and one of the through holes in the main path are the same through hole (i.e., shared through hole), the end point of each branch path and another one of the through holes in the main path are the same through hole (i.e., shared through hole); and the remaining through holes in the branch path are not shared through holes, so that both ends of the branch path are communicated with the main path. In this way, the sample can simultaneously flow from one of the shared through holes on the main path to the through hole downstream and adjacent to the shared through hole on the main path and the through hole downstream and adjacent to the shared through hole on the branch path corresponding to the shared through hole, and then the sample flowing through the branch path is merged with the sample flowing through the main path at the shared through hole corresponding to the end point of the branch path.
On this basis, for each shared through hole, the first flow channel 21 or the second flow channel 31 communicated with the shared through hole is communicated with the through hole 11, upstream or downstream, adjacent to the shared through hole on the main path, and communicated with the through hole, upstream or downstream, adjacent to the shared through hole on the branch path where the shared through hole is located. That is, the first flow channel 21 or the second flow channel 31 communicated with the shared through hole can communicate three adjacent through holes (one through hole on the main path and two through holes on two branch paths adjacent to the through hole on the main path) or four adjacent through holes (two adjacent through holes on the main path and two through holes on two branch paths adjacent to an upstream one of the two adjacent through holes on the main path) together, thereby realizing the communication between both ends of each branch path and the main path.
There are various ways in which the flow path is formed by the combination of the at least one main path and the at least one branch path. In some implementations, as shown in
Furthermore, as shown in
On this basis, by taking the second flow channel 31a communicated with the through hole 11a serving as the shared through hole as an example, as shown in
In addition, as shown in
It should be noted that, the embodiment is not limited to the main path and the branch paths described above. In practical applications, the number and the arrangement of the main paths and the branch paths may be arbitrarily designed according to the arrangement of the through holes.
It should be noted that, in practical applications, according to different flow paths, the first flow channel structure of the first cover plate 2 may include one or a combination of the first flow channel 21 (with the shape of one long circle), the first flow channel 21a (with the shape of three long circles) and the first flow channel 21b (with the shape of two long circles); the second flow channel structure of the second cover plate 3 may include one or a combination of the second flow channel 31 (with the shape of one long circle), the second flow channel 31a (with the shape of three long circles) and the second flow channel 31b (with the shape of two long circles).
Other structures and functions of the chip packaging structure provided in this embodiment are the same as those of the first embodiment, and are not described herein again.
Compared with the first embodiment, the chip packaging structure provided in this embodiment also includes the sample substrate 1, the first cover plate 2 and the second cover plate 3, and the at least one pair of the sample inlet 4 and the sample outlet 5. The structures and functions of these components are the same as those in the first embodiment, but the difference between the first embodiment and the third embodiment is that a plurality of pairs of sample inlets and sample outlets are included.
Specifically, in order to increase the speed that the sample is introduced, the through holes are arranged in a square array, the number of the pairs of the sample inlets and the sample outlets is the same as the number of rows or columns of the square array, and all the through holes in each row or each column of the square array are correspondingly located on the flow path between each pair of the sample inlet and the sample outlet. For example, as shown in
It should be noted that the manner of simultaneously introducing the sample through the sample inlets is not limited to adopting the flow path provided in the third embodiment, and any path may be adopted, which is not particularly limited in the present disclosure.
Other structures and functions of the chip packaging structure provided in this embodiment are the same as those of the first embodiment, and are not described herein again.
In this embodiment, on the basis of the chip packaging structure provided in any one of the first to third embodiments, the first cover plate 2 and the second cover plate 3 are used as packaging cover plates of the sample substrate 1, that is, the first cover plate 2 and the second cover plate 3 together with the sample substrate 1 form a chip.
Specifically, the sample substrate 1, the first cover plate 2, and the second cover plate 3 may adopt the chip packaging structure provided in any one of the first to third embodiments. By taking the chip packaging structure provided in the first embodiment as an example, the sample substrate 1 includes a through hole region and a non-through hole region (where no through hole is arranged), and the through holes 11 are located in the through hole region. Moreover, each of the first cover plate 2 and the second cover plate 3 may be slid with respect to the sample substrate 1, so that the first flow channel structure on the first cover plate 2 and the second flow channel structure on the second cover plate 3 may be located in the through hole region and communicated with the through holes 11, or may be located in the non-through hole region and isolated from the through holes 11.
As shown in
In practical applications, the surfaces of the sample substrate 1, the first cover plate 2 and the second cover plate 3 which are attached to each other are smooth surfaces, which ensures that the sample substrate 1, the first cover plate 2 and the second cover plate 3 are closely attached to each other, and the sample in the sample substrate 1 is isolated from outside.
In some implementations, the plurality of through holes 11 are arranged in a square array, and a spacing region between every two adjacent rows of through holes and between every two adjacent columns of through holes in the array forms the non-through hole region, and a width of the spacing region is greater than a width of each of the first flow channel structure and the second flow channel structure, so as to ensure that each of the first flow channel structure and the second flow channel structure can be isolated from the through holes 11 during being located in the spacing region. On this basis, each of the first cover plate 2 and the second cover plate 3 may be slid once with respect to the sample substrate 1 along a diagonal direction of the square array (e.g., a direction E in
This embodiment provides an improvement for the sample substrate on the basis of the chip packaging structure provided in any one of the first to fourth embodiments. Specifically, a plurality of the sample substrates are included and sequentially attached to each other in a direction from the first cover plate 2 to the second cover plate 3, each sample substrate includes the through hole region and the non-through hole region, and each through hole is located in the through hole region.
In addition, each two adjacent sample substrates may be slid with respect to each other, so that through holes in one of the two adjacent sample substrates are located in the through hole region of the other sample substrate and coincide with the through holes in the other sample substrate, and in this case each sample substrate is in a state of introducing a sample; or, the through holes in one of the two adjacent sample substrates are located in the non-through hole region of the other sample substrate and isolated from the through holes in the other sample substrate, and each sample substrate is in a sealing state.
In some implementations, the through holes in each sample substrate are arranged in a square array, a spacing region between every two adjacent rows of through holes and between every two adjacent columns of through holes in the array is the non-through hole region, and a width of the spacing region is greater than two times a diameter of each through hole, so as to ensure that the through holes in one sample substrate are located in the non-through hole region of the other sample substrate and are isolated from the through holes in the other sample substrate.
As shown in
Specifically, as shown in
During the four sample substrates are in the state of introducing the sample, firstly, the first substrate 1A is kept still, and the second substrate 1B is slid in a first direction F1 on the plane parallel to the sample substrates, until each through hole 11B in the second substrate 1B is located in the spacing region between two corresponding adjacent through holes 11A in the first substrate 1A, and is in the same row as the through holes 11A in the first substrate 1A, as shown in a part (b) of
It should be noted that, in a case where a plurality of sample substrates are included, the first cover plate 2 and the second cover plate 3 may also serve as the packaging cover plates for the sample substrates 1, that is, the first cover plate 2 and the second cover plate 3 together with the sample substrates 1 form a chip. In this case, after the sample is introduced for the sample substrates 1 by using the first cover plate 2 and the second cover plate 3, the first cover plate 2 and the second cover plate 3 may be packaged to isolate the samples in two sample substrates 1, adjacent to the first cover plate 2 and the second cover plate respectively, from outside. The specific packaging manner is that the first cover plate 2 and the second cover plate 3 may be slid with respect to the sample substrates 1. The specific manner has been described in detail in the fourth embodiment and is not described herein again. Alternatively, after the sample being introduced for the sample substrates 1 by using the first cover plate 2 and the second cover plate 3, the first cover plate 2 and the second cover plate 3 may be peeled off from the sample substrates 1, and then other packaging cover plates are attached to the surfaces, to which the first cover plate 2 and the second cover plate 3 are previously attached (which will be described in detail later), so that the samples in two sample substrates 1 adjacent to the other packaging cover plates are isolated from outside. For the other sample substrates 1, the samples are isolated from outside in the way of sliding the sample substrates with respect to each other in the fifth embodiment. In this case, the sample substrates 1 and the attached packaging cover plates form a chip, and the first cover plate 2 and the second cover plate 3 are only used for introducing the sample and are peeled off after the sample being introduced.
The chip packaging structure provided in this embodiment is a variation of the fifth embodiment. In this embodiment, a plurality of sample substrates are included and are sequentially attached to each other in a direction from the first cover plate 2 to the second cover plate 3, each two adjacent sample substrates can be slid with respect to each other. Each sample substrate includes the through hole region and the non-through hole region, and the through holes in each sample substrate are arranged in a square array and located in the through hole region. Furthermore, a region of each sample substrate outside the array is the non-through hole region, which can accommodate the entire square array. However, the embodiment is not limited thereto. In practical applications, the plurality of through holes 11 may also be arranged in an array of any other shape as desired, for example, a rectangular array, a circular array, a honeycomb array, or the like. Alternatively, the plurality of through holes 11 may also be arranged in other manners, instead of being arranged in an array, which is not limited in the present disclosure, as long as the non-through hole region can accommodate all of the through holes of each sample substrate 1.
Specifically, by taking four sample substrates as an example, the state of introducing the sample is the same as the state of the four sample substrates shown in parts (a) and (c) of
This embodiment provides an improvement of the sample substrate on the basis of the chip packaging structure provided in any one of the first to fifth embodiments. In this embodiment, a second flow channel structure is disposed on a surface of the first cover plate away from the sample substrate, and a first flow channel structure is disposed on a surface of the second cover plate away from the sample substrate, so that the first cover plate and the second cover plate form two multi-role cover plates with identical structures; the two multi-role cover plates are staggered in the thickness direction of the sample substrate (i.e., the direction in which the thickness of the sample substrate extends), so that the sample inlet in one multi-role cover plate does not overlap with the other multi-role cover plate.
Specifically, in the embodiment, as shown in
In some implementations, as shown in
That is, each multi-role cover plate 8 has the first flow channel structure and the second flow channel structure, and thus may serve as the first cover plate or the second cover plate. In a case of a plurality of sample substrates being included, each multi-role cover plate 8 may serve as both the first cover plate and the second cover plate. Therefore, a uniform specification of the cover plate can be realized, which facilitates the processing of products. Moreover, the sample inlet 4 and the sample outlet in each multi-role cover plate 8 do not overlap with the other multi-role cover plates 8, so that the sample inlet 4 and the sample outlet are directly connected to outside, and the sample can be more conveniently added to the sample inlets 4 in the multi-role cover plates 8 simultaneously.
In some implementations, as shown in
It should be noted that each multi-role cover plate 8 may serve as a packaging cover plate of the sample substrate 1, that is, the multi-role cover plates 8 and the sample substrate 1 together form a chip. In this case, after the sample being introduced for the sample substrates 1 by using the multi-role cover plates 8, the multi-role cover plates 8 may be packaged to isolate the sample in the sample substrates 1 from outside. The specific packaging manner is that the multi-role cover plates 8 may be slid with respect to the sample substrates 1, as that in the chip packaging structure provided in the fourth embodiment. Alternatively, the multi-role cover plates 8 may be packaged in any other packaging manner. Alternatively, after the sample being introduced for the sample substrates 1 by using the multi-role cover plates 8, the multi-role cover plates 8 may be peeled off from the sample substrates 1, and then other packaging cover plates are attached to the surfaces of the sample substrates 1, to which the multi-role cover plates 8 are previously attached, so that the sample in the sample substrates 1 is isolated from outside. In this case, the sample substrates 1 and the attached packaging cover plates form a chip, and the multi-role cover plates 8 are used for introducing the sample and are peeled off after the sample being introduced.
In a case where a plurality of sample substrates are included between two adjacent multi-role cover plates 8, the multi-role cover plates 8 may also serve as the packaging cover plates for the sample substrates 1, that is, the multi-role cover plates 8 together with the sample substrates 1 form a chip. Alternatively, after the sample being introduced for the sample substrates 1 by using the multi-role cover plates 8, the multi-role cover plates 8 may be peeled off from the sample substrates 1, and then other packaging cover plates are attached to the surfaces of the sample substrates 1, to which the multi-role cover plates 8 are previously attached, so that samples in two sample substrates 1 adjacent to the multi-role cover plates 8 are isolated from outside. For the other sample substrates 1, the samples are isolated from outside in the way of sliding the sample substrates with respect to each other in the fifth embodiment.
This embodiment further provides a chip packaging method for the chip packaging structure provided in any one of above embodiments except for the fourth embodiment, including following steps 1 to 9.
Step 1, as shown in a part (a) in
Step 2, as shown in a part (b) in
Step 3, as shown in the part (b) in
Step 4, injecting the sealing medium into the sealing groove 71 from the inlet 71a until the sealing medium fully fills the sealing groove 71 and flows out from the outlet 71b.
Step 5, blocking the inlet 71a and the outlet 71b, and then turning over the whole chip packaging structure by 180°.
Step 6, as shown in a part (c) of
Step 7, as shown in the part (c) of
Step 8, injecting a sealing medium into a sealing groove 71 from an inlet 71a of the another sealing cover plate 7 until the sealing medium fully fills the sealing groove 71 and flows out from an outlet 71b.
Step 9, blocking the inlet 71a and the outlet 71b of the another sealing cover plate 7.
Therefore, after the sample being introduced for the sample substrate 1 by using the first cover plate 2 and the second cover plate 3, the first cover plate 2 and the second cover plate 3 may be peeled off from the sample substrate 1, and then the packaging cover plates 7 are attached to the surfaces of the sample substrate 1, to which the first cover plate 2 and the second cover plate 3 are previously attached, so that the sample in the sample substrate 1 is isolated from outside. In this case, the sample substrate 1 and the attached packaging cover plates 7 form a chip, and the first cover plate 2 and the second cover plate 3 are used for introducing the sample and are peeled off after the sample being introduced.
In practical applications, each packaging cover plate 7 may be attached to the sample substrate 1 by using glue (e.g., UV glue, etc.). Further, after the injection for the sealing medium is completed, the inlet 71a and the outlet 71b of each sealing cover plate 7 may be blocked with glue (e.g., UV glue, etc.). Furthermore, the glue and the sealing cover plate 7 are both made of a transparent material (the material of the sealing cover plate 7 is, for example, glass), which is convenient for observing.
In some implementations, for the chip packaging structure (including the plurality of sample substrates) provided in the fifth embodiment, after the step 9 is completed, the method further includes following step 10.
Step 10, keeping a first sample substrate (for example, the first substrate 1A in
Therefore, samples in the sample substrates are independent from each other, and no obstacle exists between the through holes in different sample substrates, which is convenient for observing.
As shown in
This embodiment further provides a chip packaging method for the chip packaging structure provided in the fourth embodiment, including following steps 1 to 3.
Step 1, as shown in a part (a) of
Step 2, injecting the sample through each sample inlet 4 until the sample fully fills the continuous channel along the flow path and flows out from each sample outlet 5, thereby completing the introducing of the sample.
Step 3, sliding each of the first cover plate 2 and the second cover plate 3 with respect to the sample substrate 1, so that the first flow channel structure and the second flow channel structure are located in the non-through hole region, thereby isolating the sample in the sample substrate 1 from outside.
In the embodiment, the first cover plate 2 and the second cover plate 3 serve as packaging cover plates of the sample substrate 1, that is, the first cover plate 2 and the second cover plate 3 together with the sample substrate 1 form a chip.
In some implementations, the plurality of through holes 11 are arranged in a square array, and a spacing region between every two adjacent rows of through holes and between every two adjacent columns of through holes in the array forms the non-through hole region, and a width of the spacing region is greater than a width of each of the first flow channel structure and the second flow channel structure. On this basis, each of the first cover plate 2 and the second cover plate 3 may be slid once with respect to the sample substrate 1 along a diagonal direction of the square array (e.g., a direction E in
In summary, in the chip packaging structure and the chip packaging method provided by the above embodiments of the present disclosure, not only the sample can fully fill all the through holes, but also no bubble is generated because the through holes penetrate through the sample substrate, thereby solving the problems that the sample cannot fully fill micropores, bubbles exist in the micropores, and the like after the sample entering into the micropores.
It should be understood that the above embodiments are merely exemplary embodiments adopted to explain the principles of the present disclosure, and the present disclosure is not limited thereto. It will be apparent to one of ordinary skill in the art that various changes and modifications may be made without departing from the spirit and scope of the present disclosure, and such changes and modifications also fall within the scope of the present disclosure.
Filing Document | Filing Date | Country | Kind |
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PCT/CN2022/083122 | 3/25/2022 | WO |