CN112980686A - Heart chip and detection method and application thereof - Google Patents

Heart chip and detection method and application thereof Download PDF

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CN112980686A
CN112980686A CN202110470766.6A CN202110470766A CN112980686A CN 112980686 A CN112980686 A CN 112980686A CN 202110470766 A CN202110470766 A CN 202110470766A CN 112980686 A CN112980686 A CN 112980686A
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substrate
fluid channel
chamber
elastic layer
heart
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CN112980686B (en
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张秀莉
王帅
罗勇
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Suzhou University
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Suzhou University
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    • C12MAPPARATUS FOR ENZYMOLOGY OR MICROBIOLOGY; APPARATUS FOR CULTURING MICROORGANISMS FOR PRODUCING BIOMASS, FOR GROWING CELLS OR FOR OBTAINING FERMENTATION OR METABOLIC PRODUCTS, i.e. BIOREACTORS OR FERMENTERS
    • C12M21/00Bioreactors or fermenters specially adapted for specific uses
    • C12M21/08Bioreactors or fermenters specially adapted for specific uses for producing artificial tissue or for ex-vivo cultivation of tissue
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    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12MAPPARATUS FOR ENZYMOLOGY OR MICROBIOLOGY; APPARATUS FOR CULTURING MICROORGANISMS FOR PRODUCING BIOMASS, FOR GROWING CELLS OR FOR OBTAINING FERMENTATION OR METABOLIC PRODUCTS, i.e. BIOREACTORS OR FERMENTERS
    • C12M41/00Means for regulation, monitoring, measurement or control, e.g. flow regulation

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Abstract

The invention relates to a heart chip, which comprises a cover plate, a first substrate, a second substrate and a bottom plate which are sequentially stacked, wherein an elastic layer is arranged between the first substrate and the second substrate; a first chamber for culturing cells is arranged on the first substrate; the second substrate is provided with a second cavity and a second communicating portion, the second communicating portion is attached to the bottom plate to form a second fluid channel, the second fluid channel is connected with the second cavity, visual indicating liquid is arranged in the second cavity and the second fluid channel, and the first cavity is communicated with the second cavity through the elastic layer. The invention measures the strength and frequency of the beating of the myocardial cells by measuring the amplitude and frequency of the periodic reciprocating motion of the visual indicating liquid in the second fluid channel, namely, the beating of the myocardial cells is converted into the vibration of the visual indicating liquid in the second fluid channel, and the strength and frequency of the integral beating of all the myocardial cells are directly observed and measured, thereby greatly improving the efficiency and accuracy of heart drug evaluation.

Description

Heart chip and detection method and application thereof
Technical Field
The invention relates to the technical field of organ chips, in particular to a heart chip and a detection method and application thereof.
Background
Screening drugs for treating heart diseases or assessing the cardiotoxicity of drugs generally involves in vitro experiments, which essentially comprise the following steps: (1) determining the effect of the drug on the electrophysiology of the cardiomyocytes; (2) the effect of the drug on the beating intensity and frequency of the cardiomyocytes was determined. The second step is usually performed by videotaping the beating cardiomyocytes, and then performing video analysis and data processing to obtain final data. The method cannot directly observe and measure the strength and frequency of the beating of the myocardial cells, the obtained data depend on the selection of the experimenter on the cells in the video, the definition of the cell outline and the setting of a plurality of software parameters, and the obtained data have randomness, inaccuracy and unrealistic property.
Disclosure of Invention
Therefore, the technical problem to be solved by the invention is to overcome the defects that the strength and frequency of the pulsation of the myocardial cell cannot be directly observed and measured, the state of the whole pulsation of all cells cannot be reflected, the efficiency is low, the accuracy is low and the like in the prior art.
In order to solve the technical problem, the invention provides a heart chip, which comprises a cover plate, a first substrate, a second substrate and a bottom plate which are sequentially stacked, wherein an elastic layer is arranged between the first substrate and the second substrate;
a first chamber for culturing cells is arranged on the first substrate;
a second cavity and a second communicating part are arranged on the second substrate, the second communicating part is attached to the bottom plate to form a second fluid channel, the second fluid channel is communicated with the second cavity, and visual indicating liquid is arranged in the second cavity and the second fluid channel;
the first chamber is connected with the second chamber through an elastic layer, when mature myocardial cells cultured in the first chamber are in pulsation, the pulsation drives the elastic layer to deform, so that the second chamber expands or contracts to drive the visual indicating liquid to reciprocate in the second fluid channel, and the strength and the frequency of the pulsation of the myocardial cells are directly measured by measuring the amplitude and the frequency of the vibration of the visual indicating liquid in the second fluid channel.
In an embodiment of the invention, a first communicating portion is further disposed on the first substrate, and the first communicating portion and the elastic layer are fitted to form a first fluid channel, and the first fluid channel is connected to the first chamber.
In one embodiment of the present invention, the first communicating portion is disposed on a side of the first substrate facing the elastic layer.
In one embodiment of the invention, the elastic layer is an elastic film capable of deforming, and the surface of the elastic film is provided with an adhesion layer.
In one embodiment of the invention, the elastic layer is provided with electrodes, or electrodes are attached to the surface of heart-related cells.
In one embodiment of the present invention, the apparatus further comprises a visualization scale disposed on the second substrate or the bottom plate, and the visualization scale is disposed near the second fluid channel.
In one embodiment of the present invention, the cover plate, the first substrate, the elastic layer, the second substrate, and the bottom plate are provided with through holes, and the cover plate, the first substrate, the elastic layer, the second substrate, and the bottom plate form a passage through the through holes.
The invention also provides a detection method for simulating the beating intensity and frequency of the myocardial cells by using the heart chip, which comprises the following steps:
adding a cell culture solution into the first chamber to culture heart-related cells, and simultaneously adding a visual indicator solution into the second chamber and the second fluid channel;
after the cardiomyocyte adhered on the elastic layer is matured, the elastic layer is driven by the beating of the cardiomyocyte to deform, so that the second cavity is expanded or contracted to drive the visual indicating liquid to reciprocate in the second fluid channel, and the beating intensity and frequency of the cardiomyocyte are directly measured by measuring the amplitude and frequency of the vibration of the visual indicating liquid in the second fluid channel.
In one embodiment of the invention, the intensity and frequency of the beating of the cardiomyocytes is determined by means of the visualization scale.
In addition, the invention also provides application of the heart chip in culturing myocardial cells in vitro, simulating heart organs and carrying out drug screening and evaluation.
Compared with the prior art, the technical scheme of the invention has the following advantages:
the invention measures the strength and frequency of the beating of the myocardial cells by measuring the amplitude and frequency of the periodic reciprocating motion of the visual indicating liquid in the second fluid channel, namely, the beating of the myocardial cells is converted into the vibration of the visual indicating liquid in the second fluid channel, and the strength and frequency of the integral beating of all the myocardial cells are directly observed and measured, thereby greatly improving the efficiency and accuracy of heart drug evaluation.
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In order that the present disclosure may be more readily and clearly understood, reference will now be made in detail to the present disclosure, examples of which are illustrated in the accompanying drawings.
Fig. 1 is a schematic structural diagram of a first embodiment of the present invention.
Fig. 2 is a schematic structural diagram of a preferred embodiment of the first embodiment of the present invention.
FIG. 3 is a schematic diagram of the beating status of the cardiomyocytes before the evodiamine is added into the drug according to the third embodiment of the present invention.
FIG. 4 is a schematic diagram of the pulsating status of cardiomyocytes after the evodiamine is dosed in example III of the present invention.
FIG. 5 is a schematic diagram of the electrophysiological status of the evodiamine-containing cardiomyocytes prior to administration in the third embodiment of the present invention.
FIG. 6 is a schematic diagram of the electrophysiological status of the cardiomyocytes after the evodiamine is dosed in example III of the present invention.
The specification reference numbers indicate: 1. a cover plate; 2. a first substrate; 3. an elastic layer; 4. a second substrate; 5. a base plate.
Detailed Description
The present invention is further described below in conjunction with the following figures and specific examples so that those skilled in the art may better understand the present invention and practice it, but the examples are not intended to limit the present invention.
Example one
Referring to fig. 1, a first embodiment of a heart chip according to the present invention is described, which includes:
referring to fig. 1, a heart chip includes a cover plate 1, a first substrate 2, an elastic layer 3, a second substrate 4 and a bottom plate 5, wherein the cover plate 1 is provided with first through holes, a part of the first through holes are used for connecting fluid pipelines, a part of the first through holes are used for inserting screws, and a part of the first through holes are used for connecting electrodes; the first substrate 2 is provided with a first chamber for culturing cells, a first communicating part and a second through hole; the elastic layer 3 is provided with a third through hole; the second substrate 4 is provided with a second chamber, a second communicating part and a fourth through hole, and the bottom plate 5 is provided with a fifth through hole for inserting a screw rod.
It is contemplated that the substrate material may be selected from one or more of quartz, glass, PMMA, PDMS polymer, polycarbonate, polyester, agarose, chitosan, PC/ABS, or sodium alginate, but may be other materials, and the invention is not limited thereto.
The cover plate 1, the first substrate 2, the elastic layer 3, after the second substrate 4 and the bottom plate 5 are laminated and attached in sequence, the cover plate 1 is communicated with the first substrate 2 through a first through hole, one surface of the first substrate 2 facing the elastic layer 3 is provided with a first communicating part, the first communicating part is attached to the elastic layer 3 to form a first fluid channel, the first fluid channel is connected with a first cavity, namely, the first substrate 2 is communicated with the elastic layer 3 through the first fluid channel, a second cavity is arranged on the second substrate 4, the elastic layer 3 connects the first cavity with the second cavity but is not communicated with the first cavity, one surface of the second substrate 4 facing the bottom plate 5 is provided with a second communicating part, the second communicating part is attached to the bottom plate 5 to form a second fluid channel, the second fluid channel is connected with the second cavity, namely, the second substrate 4 is communicated with the bottom plate 5 through the second fluid channel.
It is contemplated that the cross-section of the first and second fluid channels may be rectangular, trapezoidal, semi-circular, or semi-elliptical, although other shapes are possible, and the invention is not limited thereto.
Wherein, the first chamber is used for culturing cells, and can be one or more of cells, cell balls, tissues and organoids, and the cells, cell balls, tissues and organoids can be originated from various organs or tissues.
Furthermore, the number of the first chambers is multiple, wherein at least one first chamber is used for culturing heart-related cells or tissues, and the first chamber for culturing the heart-related cells or tissues is connected with the second chamber through the elastic layer 3, that is, the second chamber is arranged right below the first chamber, that is, the elastic layer 3 is not only the bottom surface of the first chamber, but also the top surface of the second chamber, so that the pulsation of the cardiomyocyte can drive the elastic layer 3 to deform, so that the second chamber expands or contracts.
Be provided with visual indicator liquid in second cavity and the second fluid passage, in order to facilitate the more directly perceived state of observing visual indicator liquid, as preferred, visual indicator liquid can be colored visual indicator liquid, for example visual indicator liquid is red, when cultivateing ripe cardiomyocyte in first cavity and beating, its beat can drive elastic layer 3 and warp for the second cavity inflation or shrink, in order to drive red visual indicator liquid reciprocating motion in the second fluid passage, through the direct intensity and the frequency of surveying the cardiomyocyte beating of the range and the frequency of visual indicator liquid vibration in the second fluid passage.
It is contemplated that the first and second chambers may be cylindrical, rectangular, or square in shape, although other shapes are possible, and the invention is not limited thereto.
It is contemplated that the visual indicator fluid may be a non-volatile fluid such as oil, which is non-volatile and can be stored for a longer period of time in the second chamber and the second fluid passageway.
Still include visual scale, visual scale sets up on second base plate 4, and visual scale is close to second fluid passage and sets up, directly surveys the intensity and the frequency of cardiomyocyte pulsation through visual scale. As a modification, the visualization scale may be provided on the bottom plate 5, and the function of directly measuring the intensity and frequency of the pulsation of the cardiomyocyte can be similarly realized.
Elastic layer 3 is the elastic membrane that can take place deformation, and the elastic membrane surface is provided with the adhesion layer, and as preferred, the elastic membrane surface is provided with the adhesion layer that is used for the relevant cell of adhesion heart for the myocardial cell adheres on the elastic membrane, so makes the beat of myocardial cell can drive the elastic membrane and warp. Of course, the adhesion layer may also be provided in the first chamber in which heart-related cells, cell spheres, tissues or organoids are cultured.
Furthermore, the present invention can simultaneously measure the electrophysiology of the myocardial cells, and an electrode, preferably a flexible electrode, can be arranged on the elastic membrane. As a modification, the surface of the cultured (which may be three-dimensional culture) cardiomyocytes is connected to an electrode, and the function of measuring the electrophysiological properties of the cardiomyocytes can be similarly achieved.
Referring to fig. 2, fig. 2 is a schematic structural diagram of a preferred embodiment of the heart chip of the present invention, which is labeled as follows: the first through holes 1-1, 1-2, 1-3 and 1-4 on the cover plate 1 are used for connecting fluid pipelines; the first through holes 1-5, 1-6, 1-7 and 1-8 are used for inserting screws; the first through holes 1-9 and 1-10 are used for connecting electrodes. First chambers 2-5, 2-6 and 2-8 on the first substrate 2 for culturing cells; a first communicating portion 2-7 for connecting the first chamber 2-5 and the first chamber 2-6, and a first communicating portion 2-11 for connecting the first chamber 2-6 and the first chamber 2-8; the second through holes 2-1, 2-2, 2-3 and 2-4 are used for connecting fluid pipelines; the second through holes 2-9 and 2-10 are used for connecting electrodes. Third through holes 3-3 and 3-4 on the elastic layer 3 are used for connecting fluid pipelines; the electrodes 3-5 and 3-6 are used to measure the electrophysiological properties of the cardiomyocytes. A second cavity 4-5 on the second substrate 4 is filled with visual indicating liquid; the second communicating part 4-6 is used for connecting the second chamber 4-5; the fourth through holes 4-3 and 4-4 are used for connecting fluid pipelines; visualization scales 4-7 are used to determine the intensity and frequency of cardiomyocytes. The fifth through holes 5-5, 5-6, 5-7 and 5-8 on the bottom plate 5 are used for inserting the screw rods.
When the cover plate 1, the first substrate 2, the elastic film, the second substrate 4 and the bottom plate 5 are closely attached, the top and bottom surfaces of the first chambers 2-5, 2-6 and 2-8 are respectively attached to the cover plate 1 and the elastic film, which forms a first chamber 2-5 with an elastic bottom surface, wherein the first chamber 2-5 can be used for culturing myocardial cells, the first chamber 2-6 can be used for three-dimensional culturing parenchymal hepatocytes, the first chamber 2-8 can be used for three-dimensional culturing adipocytes, and a first communicating part 2-7 and an elastic membrane are attached to form one of the first fluid channels, the first fluid channel connects the first chamber 2-5 and the first chamber 2-6, and similarly, the first communicating portion 2-11 and the elastic membrane are attached to form another first fluid channel, and the first fluid channel connects the first chamber 2-6 and the first chamber 2-8.
Wherein the first through hole 1-1 on the cover plate 1, the second through hole 2-1 on the first substrate 2 and the elastic membrane form one passage, the first through hole 1-2 on the cover plate 1, the second through hole 2-2 on the first substrate 2 and the elastic membrane form the other passage, and cell culture solution and medicines can be added into the first chambers 2-5, 2-6 and 2-8 through the two passages.
The top and bottom surfaces of the second chamber 4-5 are attached to the elastic membrane and the bottom plate 5, respectively, which form the second chamber 4-5 having an elastic top surface, and a second communicating portion 4-6 is attached to the bottom plate 5 to form a second fluid passage communicating with the second chamber 4-5.
Wherein a first through hole 1-3 on the cover plate 1, a second through hole 2-3 on the first substrate 2, a third through hole 3-3 on the elastic membrane, a fourth through hole 4-3 on the second substrate 4 and the bottom plate 5 form one of the passages, wherein the first through hole 1-4 on the cover plate 1, the second through hole 2-4 on the first substrate 2, the third through hole 3-4 on the elastic membrane, the fourth through hole 4-4 on the second substrate 4 and the bottom plate 5 form another channel, through these two passages, the second chamber 4-5 and the second fluid channel can be filled with a visual indicator liquid, wherein the second chamber 4-5 and the visual indicator fluid in the second fluid pathway may be the same fluid, for example red oil, which fills the second chamber 4-5 and is poured half way down the visual scale 4-7. When the myocardial cells adhered to the elastic membrane are mature, the myocardial cells begin to beat, so that the elastic membrane is subjected to periodic deformation, the second chamber 4-5 is expanded or contracted to drive the red visual indicating liquid to reciprocate in the second fluid channel, and the beating intensity and frequency of the myocardial cells are directly measured through the intensity and frequency of vibration of the visual indicating liquid in the second fluid channel.
The strength and the frequency of the beating of the myocardial cells are directly measured through the strength and the frequency of the movement of the visual indicating liquid in the second fluid channel, namely the beating of the myocardial cells is converted into the reciprocating movement of the visual indicating liquid in the second fluid channel, so that the strength and the frequency of the integral beating of all the myocardial cells are directly observed and measured, the state of the integral beating of all the myocardial cells can be reflected, and the efficiency and the accuracy of heart drug evaluation are greatly improved.
The invention can integrate other organs, such as liver organs, to directly research the cardiotoxicity or drug effect of drug liver metabolites, and further integrate more other organs to simulate human body, so as to measure the cardiotoxicity or drug effect of drugs in the environment of human body simulation, that is, the invention finally provides a brand-new and highly bionic in-vitro platform for screening cardiodrugs.
Example two
The second embodiment of the detection method for simulating the beating intensity and frequency of the cardiomyocyte provided by the invention is described below by taking the preferred embodiment shown in fig. 2 in the first embodiment as an example.
A detection method for simulating the beating intensity and frequency of a myocardial cell by using a heart chip (here, the heart chip in the first embodiment) comprises the following steps:
s10, adding cell culture solution into the first chamber 2-5 to culture the heart-related cells, and simultaneously adding visual indicator solution into the second chamber 4-5 and the second fluid channel.
Illustratively, referring to fig. 2, a cardiomyocyte culture solution, a hepatocyte culture solution, and an adipocyte culture solution are respectively added to the first chambers 2-5, 2-6, and 2-8 through two passages (1-1, 2-1, 3 constituting one passage and 1-2, 2-2, 3 constituting the other passage) formed by the cover plate 1, the first substrate 2, and the elastic membrane.
Illustratively, with continued reference to fig. 2, two passages (1-3, 2-3, 3-3, 4-3, 5 constituting one passage and 1-4, 2-4, 3-4, 4-4, 5 constituting the other passage) formed by the cover plate 1, the first substrate 2, the elastic membrane, the second substrate 4 and the bottom plate 5 are filled with red oil into the second chamber 4-5 and the second fluid channel, the red oil is filled in the second chamber 4-5 until the red oil is filled in a half of the visual scale 4-7, and then the through holes (1-3, 2-3, 3-3, 4-3, 5) are blocked, leaving the through holes (1-4, 2-4, 3-4, 4-4, 5) open.
S20, after the cardiomyocyte adhered on the elastic membrane is mature, the elastic membrane is driven to deform by the pulsation of the cardiomyocyte, so that the second chamber 4-5 is expanded or contracted to drive the visual indicating liquid to reciprocate in the second fluid channel, the pulsating strength and frequency of the cardiomyocyte are directly measured by the vibration amplitude and frequency of the visual indicating liquid in the second fluid channel, and the pulsating strength and frequency of the cardiomyocyte are measured by the visual scale.
EXAMPLE III
The third embodiment of the application of the heart chip provided by the invention is described below, and the third embodiment is realized based on the first embodiment and the second embodiment, and is expanded to a certain extent on the basis of the first embodiment and the second embodiment.
This example provides the application of the heart chip in vitro culture of cardiomyocytes, and the specific structure of the heart chip, the marks of the through holes and the marks of the chambers are shown in fig. 2. Specific contents of the dirty chip in fig. 2 have been elaborated in the first embodiment, and this embodiment is not described herein again.
In this embodiment, referring to fig. 2, a cell culture solution may be added into the first chamber 2-5 for performing heart-related cell culture, for example, a cardiomyocyte culture solution, a hepatocyte culture solution and an adipocyte culture solution may be added into the first chamber 2-5, 2-6 and 2-8 through two passages (1-1, 2-1, 3 constitutes one passage and 1-2, 2-2, 3 constitutes the other passage) formed by the cover plate 1, the first substrate 2 and the elastic membrane, respectively.
Example four
An application example of the heart chip provided by the present invention is described below, and the example four is implemented based on the above example three and is expanded to a certain extent based on the example three.
The embodiment provides an application of a heart chip in simulating heart organs and performing drug screening and evaluation, and the specific structure of the heart chip, the marks of through holes and the marks of chambers are shown in fig. 2. Specific contents of the dirty chip in fig. 2 have been elaborated in the first embodiment, and this embodiment is not described herein again.
In this embodiment, referring to FIG. 2, two passages (1-1, 2-1, 3 constituting one passage and 1-2, 2-2, 3 constituting the other passage) formed by the cover plate 1, the first base plate 2 and the elastic membrane are filled with a cardiomyocyte culture solution, a hepatocyte culture solution and an adipocyte culture solution into the first chambers 2-5, 2-6 and 2-8, respectively, to perform cell culture, and two passages (1-3, 2-3, 3-3, 4-3, 5 constituting one passage and 1-4, 2-4, 3-4, 4-4, 5 constituting the other passage) formed by the cover plate 1, the first base plate 2, the elastic membrane, the second base plate 4 and the bottom plate 5 are filled with a red oil into the second chambers 4-5 and the second fluid channel, the second chamber 4-5 is filled with red oil, and the red oil is poured to half of the visual scale 4-7, and then the through holes (1-3, 2-3, 3-3, 4-3, 5) are blocked, and the through holes (1-4, 2-4, 3-4, 4-4, 5) are left open.
After the cardiomyocyte adhered to the elastic membrane is mature, the cardiomyocyte starts to beat, so that the elastic membrane is subjected to periodic deformation, the second chamber 4-5 is expanded or contracted to drive the red visual indicating liquid to reciprocate in the second fluid channel, namely the visual indicating liquid is subjected to periodic expansion and contraction in the second fluid channel, and the frequency and the intensity of beating of the cardiomyocyte can be visually judged according to the expansion and contraction rate and intensity of the visual indicating liquid.
Firstly, recording the frequency and intensity of the beating of the myocardial cells by using a visual scale (as shown in figure 3), recording electrophysiological signals by using electrodes (3-5, 3-6) (as shown in figure 5), then adding evodiamine into the chip through a passage (a passage formed by a first through hole 1-2, a second through hole 2-2 and an elastic membrane), wherein the evodiamine firstly flows through fat cells in a first chamber 2-8, is metabolized by fat, then flows through three-dimensional cultured liver cells in the first chamber 2-6, is metabolized by the liver cells, metabolites and raw drugs further flow into the first chamber 2-5 to interact with the myocardial cells, and after 24 hours, the frequency and intensity of the beating of the myocardial cells (the result is shown in figure 4) and the electrophysiological signals (the result is shown in figure 6) are recorded.
From fig. 3 to fig. 6, it can be seen that after the effect of the cardiomyocyte and the evodiamine and the metabolite thereof, the beating frequency of the cardiomyocyte becomes faster, which indicates that the evodiamine and the metabolite thereof have the effect of accelerating heartbeat, and the combination of the change of the electrophysiological signal of the cardiomyocyte indicates that the evodiamine has certain cardiotoxicity.
It should be understood that the above examples are only for clarity of illustration and are not intended to limit the embodiments. Other variations and modifications will be apparent to persons skilled in the art in light of the above description. And are neither required nor exhaustive of all embodiments. And obvious variations or modifications of the invention may be made without departing from the spirit or scope of the invention.

Claims (10)

1. A heart chip, comprising: the elastic layer is arranged between the first substrate and the second substrate;
a first chamber for culturing cells is arranged on the first substrate;
a second cavity and a second communicating part are arranged on the second substrate, the second communicating part is attached to the bottom plate to form a second fluid channel, the second fluid channel is communicated with the second cavity, and visual indicating liquid is arranged in the second cavity and the second fluid channel;
the first chamber is connected with the second chamber through an elastic layer, when mature myocardial cells cultured in the first chamber are in pulsation, the pulsation drives the elastic layer to deform, so that the second chamber expands or contracts to drive the visual indicating liquid to reciprocate in the second fluid channel, and the pulsation intensity and frequency of the myocardial cells are directly measured through the vibration amplitude and frequency of the visual indicating liquid in the second fluid channel.
2. The heart chip of claim 1, wherein: the first substrate is further provided with a first communicating part, the first communicating part and the elastic layer are attached to form a first fluid channel, and the first fluid channel is connected with the first cavity.
3. The heart chip of claim 2, wherein: the first communicating part is arranged on one surface of the first substrate, which faces the elastic layer.
4. The heart chip of claim 1, wherein: the elastic layer is an elastic film capable of deforming, and an adhesion layer is arranged on the surface of the elastic film.
5. A cardiac chip as claimed in claim 1 or 4, wherein: the elastic layer is provided with electrodes, or the surfaces of the heart-related cells are connected with the electrodes.
6. The heart chip of claim 1, wherein: the second substrate is provided with a bottom plate, the bottom plate is provided with a second fluid channel, and the bottom plate is provided with a second base plate and a second base plate.
7. The heart chip of claim 1, wherein: the cover plate, the first substrate, the elastic layer, the second substrate and the bottom plate form a passage through the through holes.
8. A method for detecting the intensity and frequency of a beating of a cardiomyocyte using a heart chip according to any one of claims 1 to 7, comprising the steps of:
adding a cell culture solution into the first chamber to culture heart-related cells, and simultaneously adding a visual indicator solution into the second chamber and the second fluid channel;
after the cardiomyocyte adhered on the elastic layer is matured, the elastic layer is driven by the beating of the cardiomyocyte to deform, so that the second cavity is expanded or contracted to drive the visual indicating liquid to reciprocate in the second fluid channel, and the beating intensity and frequency of the cardiomyocyte are directly measured by measuring the amplitude and frequency of the vibration of the visual indicating liquid in the second fluid channel.
9. The detection method according to claim 8, characterized in that: the intensity and frequency of the beating of the cardiomyocytes was determined by visual scale.
10. Use of a heart chip according to any one of claims 1 to 7 for culturing cardiomyocytes in vitro, for simulating heart organs and for drug screening evaluation.
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