The disclosure claims priority to Chinese Patent Application No. 202010877864.7, entitled “DETECTION CHIP, PREPARATION METHOD AND USE METHOD THEREOF, AND DETECTION DEVICE”, filed with the China National Intellectual Property Administration on Aug. 27, 2020, which is incorporated herein by reference in its entirety.
The embodiments of the disclosure relate to a detection chip, a preparation method and use method thereof, and a detection device.
The micro-fluidic chip technique may automatically complete a whole reaction and analysis process by integrating basic operation units for sample preparation, reaction, separation and detection in biological, chemical and medical fields on a chip with a micro-channel on the micrometer scale. The chip used in this process is called a micro-fluidic chip, referred to as a Lab-on-a-chip. The micro-fluidic chip technique has the advantages of being low in sample consumption, high in analysis speed, beneficial to fabrication of portable instruments, suitable for instant field analysis, and the like, thus having been widely applied to the biological, chemical and medical fields as well as many other fields.
At least one embodiment of the disclosure provides a detection chip, comprising:
a substrate comprising a piercing structure; and
a reservoir chamber configured to contain a liquid and comprising a support frame, and a first seal layer and a second seal layer for sealing the support frame;
wherein, the support frame comprises a support frame body and a cavity formed in the middle of the support frame body; and
the second seal layer is configured to be concaved into the reservoir chamber.
Optionally, a contour of the second seal layer is approximately shaped like a hemisphere that is concaved into the reservoir chamber.
Optionally, the second seal layer comprises a polymer layer and a metal layer.
Optionally, the second seal layer comprises an aluminum film and a PE polymer layer.
Optionally, the second seal layer comprises a metal film.
Optionally, the first seal layer is a flexible polymer film and is configured to deform when pressed.
Optionally, the PE polymer layer has a thickness of 0.001 mm to 1 mm, and the aluminum film has a thickness of 0.001 mm to 1 mm.
Optionally, the substrate further comprises a connecting portion that is configured to be connected to the reservoir chamber.
Optionally, the connecting portion comprises a bump with a circular cross-section, and a height of the bump is greater than a concave depth of the second seal layer.
Optionally, the piercing structure is a needle tip, and a distance from a top end of the needle tip to a surface, away from the substrate, of the bump is smaller than the concave depth of the second seal layer.
Optionally, the reservoir chamber is fixedly connected to the bump and is coaxially aligned with the bump.
Optionally, the piercing structure is located at a center of the cross-section shape of the connecting portion.
Optionally, the piercing structure is a needle tip.
Optionally, the piercing structure is formed with a micro-channel opening that is configured to be communicated with a micro-channel in the substrate.
Optionally, in case where the detection chip is used for immunological detection, the substrate is made of PS or PMMA; or
in case where the detection chip is used for molecular detection, the substrate is made of PP or PC.
At least one embodiment of the disclosure provides a detection device, comprising:
the above detection chip; and
a force application mechanism configured to apply a force towards an internal space of the reservoir chamber to the first seal layer of the reservoir chamber of the detection chip to enable the second seal layer to deform to be pierced by the piercing structure.
At least one embodiment of the disclosure provides a method for operating the above detection chip, comprising:
applying a force towards an internal space of the reservoir chamber to the first seal layer of the reservoir chamber of the detection chip to enable the second seal layer to deform to be pierced by the piercing structure.
At least one embodiment of the disclosure provides a preparation method of the above detection chip, comprising:
pre-deforming the second seal layer to make the reservoir chamber; and
providing the substrate comprising a connecting portion, and fixing the reservoir chamber to the connecting portion.
Optionally, the step of pre-deforming the second seal layer comprises:
fixing the second seal layer to the support frame body to cover the cavity;
suspending a slide bar in a vertical direction of the second seal layer, wherein the vertical direction is a direction perpendicular to a surface of the second seal layer; and
controlling the slide bar to move cyclically along a preset track to enable the second seal layer to be concaved into the cavity, wherein the preset track is a motion track of the slide bar after an end of the slide bar presses against the surface of the second seal layer.
Optionally, further comprising:
pre-deforming the second seal layer by a hot-pressing or hot-extrusion process.
The aforesaid description is merely a brief summary of the technical solution of the disclosure. To allow those skilled in the art to gain a better understanding of the technical means of the disclosure so as to implement the disclosure according to the contents in the specification and to make the above and other purposes, features and advantages of the disclosure clearer, specific implementations of the disclosure are given below.
To more clearly explain the technical solutions of the embodiments of the disclosure, drawings of the embodiments will be briefly introduced below. Obviously, the drawings in the following description only relate to some embodiments of the disclosure, and are not intended to limit the disclosure.
To make the purposes, technical solutions and advantages of the embodiments of the disclosure clearer, the technical solutions of the embodiments of the disclosure will be clearly and comprehensively described below in conjunction with the drawings of the embodiments. Obviously, the embodiments in the following description are merely illustrative ones, and are not all possible ones of the disclosure. All other embodiments obtained by those ordinarily skilled in the art based on the following ones without creative labor should also fall within the protection scope of the disclosure.
Unless otherwise defined, all technical terms or scientific terms in this disclosure should have ordinary meanings understood by those with common skills in the art. “First”, “second” and similar terms in this disclosure do not indicate any sequence, quantity or relative importance, and are merely used to distinguish different constituent parts. Similarly, “one”, “a/an”, “said” and other similar terms do not indicate a quantitative limitation, and only indicate the existence of at least one. “Comprise”, “include” or other similar terms are intended to point out that an element or object appearing before the term contains an element or object or equivalents thereof listed after the term, and shall not exclusive of other elements or objects. “Connection”, “connect” or other similar terms are not limited to physical or mechanical connection, and may also refer to direct or indirect electrical connection. “Upper”, “lower”, “left” or “right” is merely used to indicate a relative positional relation, and when the absolute position of an object referred to is changed, this relative positional relation may change correspondingly.
Existing micro-fluidic chips pre-store a liquid reagent generally through a reagent storage structure and quantitatively release the liquid reagent when needed. The reagent is pre-stored in a sealed space and is isolated from the outside to be preserved for a long time; and when the chip works, the sealed space will be destroyed to allow the reagent to be quantitatively released. Whether a micro-fluidic chip is suitable for quantitative analysis of a detection result depends on whether this chip is capable of quantitatively releasing a reagent pre-stored therein.
To solve at least one of the above-mentioned problems, at least one embodiment of the disclosure provides a detection chip that is capable of quantitatively releasing liquids stored therein and is simple in structure and preparation process and low in cost.
It should be understood that the detection chip provided by the embodiments of the disclosure may be, but not limited to, a micro-fluidic chip.
At least one embodiment of the disclosure provides a detection chip. The detection chip comprises a substrate 200 and a reservoir chamber 100. The substrate may be a chip substrate. The reservoir chamber 100 comprises a support frame 130, and a first seal layer 110 and a second seal layer 120 for sealing the support frame 130. The support frame 130 comprises a support frame body 131 and a cavity 132 formed in the middle of the support frame body 131. Wherein, the second seal layer 120 is configured to be concaved into the cavity 132. The second seal layer 120 is pre-deformed, so that an external drive force for turning and deforming is reduced, and reagent residues caused by wrinkles on the seal layer is reduced to realize quantitative release.
The detection chip provided by some embodiments of the disclosure will be described below in conjunction with
As shown in
The substrate 200 may be made of any appropriate materials as actually needed, such as glass, silicon, quartz, polyethylene terephthalate (PET), polystyrene (PS), poly (methyl methacrylate) (PMMA), polypropylene (PP), polycarbonate (PC), or a combination thereof, and the embodiments of the disclosure have no limitation in this aspect. For example, when the detection chip is used for immunological detection, the substrate 200 may be made of PS or PMMA; or, when the detection chip is used for molecular detection, the substrate 200 may be made of PP or PC.
As shown in
For example, the first seal layer 110 is a flexible film made of polymer materials, has certain elasticity and strength, and is able to deform under an external drive force to apply a positive pressure to one part of the cavity 132 in the middle of the support frame body 131 sealed by the first seal layer 110. For example, the second seal layer 120 is a flexible composite film consisting of a polymer layer and a metal layer, wherein the polymer layer is flexible and ductile and endows the composite film with ductility and deformability, and the metal layer, as a support layer of the composite film, endows the composite film with certain plasticity, so that the second seal layer 120 can be maintained in a deformed state for a long time when deformed under an external force.
For example, the second seal layer 120 may be pre-deformed to be concaved inwards and has ductility and plasticity, so that the shape of the second seal layer 120 can be maintained for a long time after the second seal layer 120 is pre-deformed. For example, the contour of the second seal layer 120 is approximately shaped like a hemisphere that is concaved towards the interior of the reservoir chamber 100. It can be understood that the approximately hemispherical shape of the second seal layer 120 refers to an arc concave shape similar to a spherical concave contour. For example, the concave depth of the second seal layer 120 after pre-deformation is not equal to the radius of the outer contour of a pre-deformed portion of the second seal layer 120. For example, the contour of the second seal layer 120 after pre-deformation is in a square shape that is concaved towards the interior of the reservoir chamber 100. Of course, the embodiments of the disclosure are not limited to this, and the second seal layer 120 may also be in other suitable shapes. It can be understood that the concave depth of the second seal layer 120 depends on the material property of the second seal layer 120 and the specific size of the support frame 130 of the reservoir chamber. For example, the thicker the polymer layer in the second seal layer 120, the greater the concave depth of the second seal layer 120, under the condition that the composite film is not broken when pre-deformed. For example, the concave depth of the second seal layer 120 caused by pre-deformation is 0.1 mm to 8 mm.
For example, in case where a force towards the interior of the reservoir chamber 100 is applied to the first seal layer 110 by means of an ejection rod, the first seal layer 110 is able to deform elastically to allow the ejection rod 310 to move by a certain distance, and then the second seal layer 120 is deformed under the effect of compressed air to turn to a convex shape from the concave shape. Because the second seal layer 120 has certain plasticity, it can be maintained in the deformed state for a long time after the force applied by the ejection rod 310 is removed. It can be understood that because the second seal layer 120 is concaved towards the interior of the reservoir chamber 100, an external drive force for turning and deforming the second seal layer 120 will be much smaller, compared with a planar design.
For example, the first seal layer 110 may be made of polyethylene terephthalate (PET) to have good elasticity and strength. Of course, the embodiments of the disclosure are not limited to this, and the first seal layer 110 may also be made of other suitable materials such as polystyrene (PS) and PET polymer composite materials to have better elasticity and strength.
For example, the second seal layer 120 is a film consisting of a polyethylene (PE) polymer layer and an aluminum film, the composite film has certain ductility by means of the PE polymer layer on the surface of the aluminum film, and the PE polymer layer will not react with the biochemical reagent and is disposed on one side of the cavity sealed by the composite film, so that the reagent can be preserved for a long time. For example, the second seal layer 120 may be a metal film. Of course, the embodiments of the disclosure are not limited to this, and the second seal layer 120 may also be made of other suitable materials.
For example, the ratio of the thickness of the PE polymer layer to the thickness of the aluminum film in the second seal layer 120 determines the property of the composite film. For example, the larger the thickness of the PE polymer layer and the smaller the thickness of the aluminum film, the better the ductility of the second seal layer, and the greater the deformability of the second seal layer; the smaller the thickness of the polymer layer and the larger the thickness of the aluminum film, the better the plasticity of the second seal layer, and the second layer can be maintained in a specific shape for a long time. For example, the thickness of the PE polymer layer ranges from 0.001 mm to 1 mm, and the thickness of the aluminum film ranges from 0.001 mm to 1 mm. For example, the thickness of the PE polymer layer is 0.005 mm, the thickness of the aluminum film is 0.003 mm, and in this case, the second seal layer 120 can be pierced easily and can be maintained in the shape at the moment it is pierced for a long time after it is pierced.
The substrate shown in
As shown in
It can be understood that the substrate 200 may be made of any appropriate materials as actually needed, such as glass, silicon, quartz, ceramic, polyethylene terephthalate (PET), polystyrene (PS), poly(methyl methacrylate) (PMMA), polypropylene (PP), polycarbonate (PC) or a combination thereof. The embodiments of the disclosure have no limitation in this aspect.
For example, when the detection chip is used for immunological detection, the substrate 200 may be made of PS or PMMA; or, when the detection chip is used for molecular detection, the substrate may be made of PP or PC.
For example, the reservoir chamber 100 is fixed to the substrate 200 by threaded connection or clamped connection or in other fixed manners, and the support frame 130 of the reservoir chamber is coaxially aligned with the bump 210. For example, the bottom of the reservoir chamber 100 is bonded on the surface of the bump 210 to form a closed environment for later detection.
As shown in
For example, in case where a force towards the interior of the reservoir chamber 100 is applied to the first seal layer 110 by means of the ejection rod 310, the first seal layer 110 is able to deform elastically to allow the ejection rod 310 to move by a certain distance, then the second seal layer 120 is deformed under the effect of compressed air to turn from the concave shape to the convex shape, the needle tip 220 pierces the second seal layer 120 at the top end of the convex hemisphere to form a break, and then the reagent in the reservoir chamber 100 is discharged along the hemispherical surface, so that reagent residues in the reservoir chamber 100 are reduced; and because the second seal layer 120 has certain plasticity, it can be maintained in the deformed state for a long time after the force applied by the ejection rod 310 is removed. It should be noted that the distance h2 from the top end of the needle tip 220 to the surface, away from the substrate 200, of the bump 210 should be smaller than the concave depth h1 of the second seal layer 120 to ensure that the second seal layer 120 contacts the needle tip 220 to be pierced after being turned during work.
For example, as shown in
For example, the piercing structure is formed with a micro-channel opening that is configured to be communicated with a micro-channel 221 in the substrate 200; and when the piercing structure pierces the second seal layer 120, the reagent in the reservoir chamber 100 flows into the detection chip along the break via the micro-channel opening in the piercing structure. The working principle of the detection chip will be illustratively described below.
Before the chip works, the reservoir chamber 100 having a specific reagent sealed therein 100 is fixed to the bump 210 of the substrate 200 by threaded connection or clamped connection or in other fixed manners, and is coaxially aligned with the bump 210. For example, the bottom of the reservoir chamber 100 is bonded on the surface of the bump 210 to form a closed environment for later detection. The reservoir chamber 100 is designed to be modular, so that different reagent combinations and different dose combinations may be used when the chip is used for detecting different items to make detection data more accurate. In this embodiment, one substrate may be provided with multiple reservoir chambers for sealing different reagents, so that costs are reduced.
The reservoir chamber 100 comprises a support frame 130, and a first seal layer 110 and a second seal layer 120 for sealing the support frame 130. The support frame comprises a support frame body and a cavity formed in the middle of the support frame body, wherein a biochemical reagent is stored in the cavity in the support frame body and is sealed by the first seal layer and the second seal layer.
The first seal layer 110 is a flexible film made of polymer materials, has certain elasticity and strength, and is able to deform under an external drive force. The second seal layer 120 is a pre-deformed flexible composite film consisting of a polymer layer and a metal layer, wherein the polymer layer is flexible and ductile and endows the composite film with ductility and deformability, and the metal layer, as a support layer of the composite film, endows the composite film with certain plasticity, so that the second seal layer 120 can be maintained in the pre-deformed state for a long time. For example, the second seal layer 120 is a composite film consisting of a PE polymer layer and an aluminum film, wherein the thickness of the PE polymer layer is 0.005 mm, the thickness of the aluminum film is 0.003 mm, and in this case, the second seal layer 120 can be easily pierced and can be maintained in the shape at the moment it is pierced for a long time after it is pierced.
Furthermore, a needle tip structure is disposed on the surface of the substrate 200 and is located at the center of the cross-section shape of the connecting portion. It can be understood that the support frame 130 of the reservoir chamber, the bump 210 and the piercing structure should be coaxially aligned before the detection chip starts to work, and at this moment, the needle tip 220 exactly corresponds to a portion, deformed to the maximum extent, of the second seal layer.
As shown in
At least one embodiment of the disclosure provides a preparation method of a detection chip, comprising: a substrate is provided, wherein the detection chip may be the detection chip provided by any one embodiment mentioned above. Please refer to the description of the above embodiments for a detailed description of the detection chip, and unnecessary details will no longer be given here.
For example, referring to
In some embodiments, the preparation method of the detection chip may further comprise: the second seal layer 120 of the reservoir chamber 100 is pre-deformed. Referring to
The support frame 130 is a support member for fixing the second seal layer 120 and comprises a support frame body 131 and a cavity 132 formed in the middle of the support frame body 131. The second seal layer 120 is fixed to the support frame body 131 with glue or in other manners. The cavity 132 is formed in the middle of the support frame body 131, so that when the second seal layer 120 covers the cavity 132, a portion, covering the cavity 132, of the second seal layer 120 is suspended and will be concaved to the bottom of the cavity 132 under the effect of the slide bar to form an accommodating cavity for containing the biochemical reagent.
Optionally, the support frame body 131 is any one selected from a circular support, a rectangular support and a rhombic support. Specifically, in case where the support frame body 131 is a circular support, the contour of the second seal layer 120 is approximately hemispherical under the effect of the slide bar 410. It should noted that the shape of the support frame body 131 depends on the shape of the accommodating cavity to be formed by the second seal layer 120, and the embodiments of the disclosure have no limitation in this aspect.
In a possible embodiment, the slide bar 410 moves cyclically to form a circular track. Illustratively, the cavity 132 in the support frame body 131 may be a cylindrical cavity with a diameter of 16 mm, a thickness of 1 mm and a depth of 6 mm, the slide bar 410 makes a circular motion with a diameter of 10 mm by taking the center of the cavity 132 in the middle of the support frame body 131 as a rotation center, then moves downwards by 1 mm in the direction perpendicular to the surface of the second seal layer 120, and then makes a circular motion with a diameter of 8 mm by taking the center of the cavity 132 in the middle of the support frame body 131 as the rotation center, and so on. As shown in
In some embodiments, the preparation method of the detection chip may further comprise: the second seal layer is pre-deformed by a hot-pressing or hot-extrusion process.
In some embodiments, the preparation method of the detection chip may further comprise: the second seal layer and the support frame are bonded by laser welding or with a binding agent. For example, when the second seal layer and the support frame are made of the same material (such as PS, PMMA, PC, PP or other polymer materials), the second seal layer and the support frame may be bonded by laser welding. When the second seal layer and the support frame are made of different materials, the seal layer and the support frame may be bonded with a binding agent. It can be understood that the second seal layer and the support frame may be bonded after the second seal layer is pre-deformed or before the second seal layer is pre-deformed.
A detection chip 510; and
A force application mechanism 520 configured to apply a force towards an internal space of the reservoir chamber to the first seal layer of the reservoir chamber of the detection chip during use to enable the second seal layer to deform to be pierced by the piercing structure to allow liquid contained in the internal space to flow into the micro-channel.
The detection chip may be the detection chip provided by any one embodiment mentioned above. The force application mechanism may be in any appropriate forms as long as it is capable of applying a force towards the reservoir chamber of the detection chip to destroy the second seal layer of the reservoir chamber of the detection chip. For example, the force application mechanism may comprise an ejection rod, as shown in
It should be understood that the detection device 300 may further comprise other components such as a base allowing the detection chip to be placed thereon, a liquid waste disposal device, various analysis detectors, a liquid inlet/outlet, and a power port which are not shown in
At least one embodiment of the disclosure further provides a method for operating a detection chip, wherein the detection chip may be the detection chip provided by any one embodiment mentioned above. Please refer to the description of the above embodiments in the specification for a detailed description of the detection chip, and unnecessary details will no longer be given here.
For example, the method for operating the detection chip according to the at least one embodiment of the disclosure may comprise:
A force towards an internal space of the reservoir chamber is applied to the first seal layer of the reservoir chamber of the detection chip to enable the second seal layer to deform to be pierced by the needle tip to allow liquid contained in the internal space to flow into the micro-channel.
“One embodiment”, “an embodiment” or “one or more embodiments” in this specification means that specific features, structures, or characteristics described in conjunction with said embodiment are included in at least one embodiment of the disclosure. In addition, it should be noted that the expression “in one embodiment” does not definitely refer to the same embodiment.
A great plenty of specific details are provided in this specification. However, it can be understood that the embodiments of the disclosure can be implemented even without these specific details. In some embodiments, known methods, structures and techniques are not stated in detail to ensure that the understanding of this specification will not be obscured.
The detection chip, the preparation method and use method thereof, and the detection device provided by the disclosure are introduced in detail above, specific examples are used in this specification to expound the principle and implementation of the disclosure, and the description of the above embodiments is merely used to assist those skilled in the art in understanding the method and core concept thereof of the disclosure. In addition, those ordinarily skilled in the art can make changes to the specific implementation and application scope based on the concept of the disclosure. So, the contents of the specification should not be construed as limitations of the disclosure.
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202010877864.7 | Aug 2020 | CN | national |
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20220062889 A1 | Mar 2022 | US |