WO2022227152A1

WO2022227152A1 - Heart chip and detection method and application thereof

Info

Publication number: WO2022227152A1
Application number: PCT/CN2021/095627
Authority: WO
Inventors: 张秀莉; 王帅; 罗勇
Original assignee: 苏州大学
Priority date: 2021-04-29
Filing date: 2021-05-25
Publication date: 2022-11-03
Also published as: CN112980686A; CN112980686B

Abstract

The present invention provides a heart chip, which comprises a cover plate, a first substrate, a second substrate, and a bottom plate which are sequentially stacked, and an elastic layer is provided between the first substrate and the second substrate. The first substrate is provided with first chambers for culturing cells; the second substrate is provided with a second chamber and a second communication portion, the second communication portion is attached to the bottom plate to form a second fluid channel, the second fluid channel is connected to the second chamber, a visual indicating liquid is provided in the second chamber and the second fluid channel, and the first chambers are communicated with the second chamber by means of the elastic layer. According to the present invention, by measuring the amplitude and frequency of periodic reciprocating movement of the visual indicating liquid in the second fluid channel, the intensity and frequency of the myocardial cell beat are measured, that is, the beat of the myocardial cells is converted into the vibration of the visual indicating liquid in the second fluid channel, the intensity and frequency of the whole beat of all myocardial cells are directly observed and metered, and therefore the efficiency and accuracy of cardiac drug evaluation are greatly improved.

Description

Cardiac chip and its detection method and application

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 technique

Screening drugs for the treatment of heart disease or evaluating the cardiotoxicity of drugs usually includes in vitro experiments. The in vitro experiments mainly include the following steps: (1) Determination of the effect of drugs on the electrophysiology of cardiomyocytes; (2) Determination of the beating intensity and frequency of cardiomyocytes Impact. Among them, the usual practice for the second step is to obtain the final data by video recording of beating cardiomyocytes, and then through video analysis and data processing. This method cannot directly observe and measure the intensity and frequency of cardiomyocyte beating, and the obtained data depends on the selection of cells in the video by the experimenter, the definition of cell contours, and the setting of multiple software parameters, which are random, Inaccuracy and inauthenticity, since the number of selected cells is always limited, the resulting data cannot reflect the overall beating state of all cells, thereby affecting the efficiency and accuracy of cardiac drug evaluation.

SUMMARY OF THE INVENTION

Therefore, the technical problem to be solved by the present invention is to overcome the defects of the prior art, such as the inability to directly observe and measure the beating intensity and frequency of cardiomyocytes, the inability to reflect the overall beating state of all cells, and the low efficiency and accuracy.

In order to solve the above technical problems, the present invention provides a heart chip, comprising a cover plate, a first substrate, a second substrate and a bottom plate that are stacked in sequence, and an elastic layer is arranged between the first substrate and the second substrate;

The first substrate is provided with a first chamber for culturing cells;

The second base plate is provided with a second chamber and a second communication portion, the second communication portion is fitted with the bottom plate to form a second fluid channel, and the second fluid channel communicates with the second chamber, A visual indicator liquid is arranged in the second chamber and the second fluid channel;

The first chamber is connected to the second chamber through an elastic layer, and when the mature cardiomyocytes cultured in the first chamber are beating, the beating will drive the deformation of the elastic layer, so that the second chamber is expanded or contraction, to drive the visual indicator fluid to reciprocate in the second fluid channel, and directly measure the intensity and frequency of the cardiomyocyte beating by measuring the amplitude and frequency of the visual indicator fluid vibrating in the second fluid channel.

In an embodiment of the present invention, a first communication portion is further provided on the first substrate, and the first communication portion is attached to the elastic layer to form a first fluid channel, and the first fluid channel is connected to the the first chamber.

In an embodiment of the present invention, the first communication portion is disposed on a side of the first substrate facing the elastic layer.

In an embodiment of the present invention, the elastic layer is a deformable elastic film, and an adhesive layer is provided on the surface of the elastic film.

In an embodiment of the present invention, the elastic layer is provided with electrodes, or electrodes are connected on the surface of the heart-related cells.

In an embodiment of the present invention, a visualization scale is further included, the visualization scale is disposed on the second substrate or the bottom plate, and the visualization scale is disposed close to the second fluid channel.

In an embodiment of the present invention, it further includes a through hole, the through hole is disposed on the cover plate, the first substrate, the elastic layer, the second substrate and the bottom plate, the cover plate, the first substrate, the elastic layer , the second substrate and the bottom plate form a via through the through hole.

In addition, the present invention also provides a method for detecting the beating intensity and frequency of cardiomyocytes using the above-mentioned heart chip, comprising the following steps:

adding a cell culture solution to the first chamber for cardiac-related cell culture, while adding a visual indicator solution to the second chamber and the second fluid channel;

After the cardiomyocytes adhering to the elastic layer mature, the pulsation of the cardiomyocytes drives the deformation of the elastic layer, so that the second chamber expands or contracts, so as to drive the visual indicator fluid to reciprocate in the second fluid channel, and pass through the second fluid channel. Measuring the amplitude and frequency of the vibration of the visual indicator fluid within the second fluid channel directly determines the strength and frequency of the cardiomyocyte beating.

In one embodiment of the present invention, the intensity and frequency of the cardiomyocyte beating are determined by the visual scale.

In addition, the present invention also provides an application of the above-mentioned heart chip for culturing cardiomyocytes in vitro, simulating a heart organ, and performing drug screening and evaluation.

The above-mentioned technical scheme of the present invention has the following advantages compared with the prior art:

The present invention measures the intensity and frequency of cardiac muscle cell pulsation by measuring the amplitude and frequency of the periodic reciprocating motion of the visual indicator liquid in the second fluid channel, that is, converting the pulsation of the cardiac muscle cell into the vibration of the visual indicator fluid in the second fluid channel, Directly observe and measure the overall beating intensity and frequency of all cardiomyocytes, greatly improving the efficiency and accuracy of cardiac drug assessment

Description of drawings

In order to make the content of the present invention easier to understand clearly, the present invention will be described in further detail below according to specific embodiments of the present invention and in conjunction with the accompanying drawings.

FIG. 1 is a schematic structural diagram of Embodiment 1 of the present invention.

FIG. 2 is a schematic structural diagram of a preferred solution in Embodiment 1 of the present invention.

Figure 3 is a schematic diagram of the state of myocardial cell beating before evodiamine is added in Example 3 of the present invention.

4 is a schematic diagram of the state of myocardial cell pulsation after evodiamine is added in Example 3 of the present invention.

FIG. 5 is a schematic diagram of the electrophysiological state of cardiomyocytes before the administration of evodiamine in Example 3 of the present invention.

FIG. 6 is a schematic diagram of the electrophysiological state of cardiomyocytes after evodiamine is added in Example 3 of the present invention.

Description of reference numerals in the description: 1. Cover plate; 2. First substrate; 3. Elastic layer; 4. Second substrate; 5. Bottom plate.

Detailed ways

The present invention will be further described below in conjunction with the accompanying drawings and specific embodiments, so that those skilled in the art can better understand the present invention and implement it, but the embodiments are not intended to limit the present invention.

Example 1

The first embodiment of a heart chip provided by the present invention will be introduced below. Referring to FIG. 1, the first embodiment 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 . The cover plate 1 is provided with first through holes, some of which are first through holes. For connecting fluid pipelines, some of the first through holes are used to insert screws, and some of the first through holes are used to connect electrodes; the first substrate 2 is provided with a first chamber and a first communication part for culturing cells and a second through hole; the elastic layer 3 is provided with a third through hole; the second base plate 4 is provided with a second chamber, a second communication part and a fourth through hole, and the bottom plate 5 is provided with a fifth through hole for inserting the screw through holes.

It is conceivable that the material of the substrate may be selected from one or more of quartz, glass, PMMA, PDMS polymer, polycarbonate, polyester, agarose, chitosan, PC/ABS or sodium alginate, Of course, other materials may also be used, and the present invention is not limited thereto.

After the cover plate 1 , the first substrate 2 , the elastic layer 3 , the second substrate 4 and the bottom plate 5 are laminated in sequence, the cover plate 1 communicates with the first substrate 2 through the first through hole, and the first substrate 2 faces the elastic layer 3 . One side is provided with a first communication part, the first communication part is attached to the elastic layer 3 to form a first fluid channel, and the first fluid channel is connected to the first chamber, that is, the first substrate 2 communicates with the elastic layer 3 through the first fluid channel, and the first fluid channel is connected to the first chamber. The two chambers are arranged on the second substrate 4, the elastic layer 3 connects the first chamber and the second chamber but does not communicate with each other. A second fluid channel is formed by being attached to the bottom plate 5, and the second fluid channel is connected to the second chamber, that is, the second substrate 4 is connected to the bottom plate 5 through the second fluid channel.

It is conceivable that the cross-sections of the first fluid channel and the second fluid channel may be rectangular, trapezoidal, semicircular or semi-elliptical, and certainly may be other shapes, which are not limited in the present invention.

The function of the first chamber is to culture cells, which can be one or more of cells, spheroids, tissues and organoids, and the cells, spheroids, tissues and organoids can be derived from various organs or organize.

Further, the number of first chambers is multiple, and at least one first chamber is used for culturing heart-related cells or tissues, and the first chamber for culturing heart-related cells or tissues is connected to the second chamber through the elastic layer 3 chamber, that is, the second chamber is directly below the first chamber, that is to say, 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 cardiomyocytes can drive the elastic layer 3 Deformed, causing the second chamber to expand or contract.

A visual indicator liquid is arranged in the second chamber and the second fluid channel. In order to observe the state of the visual indicator liquid more intuitively, preferably, the visual indicator liquid can be a colored visual indicator liquid. For example, the visual indicator liquid is Red, when the mature cardiomyocytes cultured in the first chamber are beating, the beating will drive the elastic layer 3 to deform, so that the second chamber expands or contracts, so as to drive the red visual indicator fluid to reciprocate in the second fluid channel. The amplitude and frequency of the visual indicator fluid vibrating within the second fluid channel directly determines the strength and frequency of the cardiomyocyte beating.

It is conceivable that the shape of the first chamber and the second chamber may be a cylinder, a rectangular parallelepiped or a cube, and of course other shapes, which are not limited in the present invention.

It is conceivable that the visual indicator liquid may be a non-volatile liquid, such as oil, which is not volatile and can be stored in the second chamber and the second fluid channel for a long time.

It also includes a visual scale, the visual scale is arranged on the second substrate 4, and the visual scale is arranged close to the second fluid channel, and the intensity and frequency of cardiomyocyte beating can be directly measured by the visual scale. As a variant, the visual scale can also be arranged on the bottom plate 5, which can also realize the function of directly measuring the intensity and frequency of the cardiac muscle cell beating.

The elastic layer 3 is an elastic film that can be deformed, and an adhesive layer is provided on the surface of the elastic film. In this way, the pulsation of the cardiomyocytes can drive the deformation of the elastic membrane. Of course, an adhesion layer can also be provided in the first chamber for culturing heart-related cells, cell spheroids, tissues or organoids.

Furthermore, the present invention can also measure the electrophysiology of cardiomyocytes at the same time, and electrodes can be arranged on the elastic membrane, and the electrodes are preferably flexible electrodes. As a variant, the surface of the cultured (which can be three-dimensional cultured) cardiomyocytes is connected with electrodes, which can also achieve the function of measuring the electrophysiological properties of the cardiomyocytes.

Please refer to FIG. 2 . FIG. 2 is a schematic structural diagram of a preferred solution of the heart chip of the present invention. The symbols in the figure are described as follows: the first through holes 1-1, 1-2, 1-3 and 1 on the cover plate 1 -4 is used to connect the fluid pipeline; the first through holes 1-5, 1-6, 1-7 and 1-8 are used to insert the screw; the first through holes 1-9 and 1-10 are used to connect the electrodes. The first chambers 2-5, 2-6 and 2-8 on the first substrate 2 are used for culturing cells; the first communication part 2-7 is used to connect the first chamber 2-5 and the first chamber 2- 6. The first communication part 2-11 is used to connect 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 to connect Fluid lines; second through holes 2-9 and 2-10 for connecting electrodes. The third through holes 3-3 and 3-4 on the elastic layer 3 are used to connect the fluid pipeline; the electrodes 3-5 and 3-6 are used to measure the electrophysiological properties of the cardiomyocytes. The second chamber 4-5 on the second substrate 4 is filled with the visual indicator liquid; the second communication part 4-6 is used for connecting the second chamber 4-5; the fourth through holes 4-3 and 4-4 are used for Connect fluid lines; visualization scales 4-7 are used to measure cardiomyocyte strength and frequency. The fifth through holes 5-5, 5-6, 5-7 and 5-8 on the bottom plate 5 are used for inserting screws.

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 close to the cover plate 1 Fitted with the elastic membrane, it constitutes a first chamber 2-5 with an elastic bottom surface, wherein the first chamber 2-5 can be used for culturing cardiomyocytes, and the first chamber 2-6 can be used for three-dimensional culturing of liver parenchyma cells , the first chamber 2-8 can be used for three-dimensional culture of adipocytes, and the first communication part 2-7 is attached to the elastic membrane to form one of the first fluid channels, and the first fluid channel is connected to the first chamber 2- 5 and the first chamber 2-6, similarly, the first communication part 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 Room 2-8.

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 film constitute one of the passages. The first through hole 1-2 on the cover plate 1, the first through hole 2-1 on the The second through hole 2-2 on the base plate 2 and the elastic membrane form another passage, through which the cell culture fluid and medicine can be added to the first chambers 2-5, 2-6, and 2-8.

The top and bottom surfaces of the second chamber 4-5 are respectively attached to the elastic membrane and the bottom plate 5, which constitute the second chamber 4-5 with an elastic top surface, and the second communicating portion 4-6 is attached to the bottom plate 5. The second fluid channel is combined to form a second fluid channel, and the second fluid channel communicates with the second chambers 4-5.

The first through hole 1-3 on the cover plate 1, the second through hole 2-3 on the first substrate 2, the third through hole 3-3 on the elastic film, and the fourth through hole on the second substrate 4 4-3 and the bottom plate 5 constitute 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, and the third through hole 3-4 on the elastic film , the fourth through hole 4-4 on the second substrate 4 and the bottom plate 5 constitute another passage, through which the visual indicator liquid can be perfused into the second chamber 4-5 and the second fluid channel, wherein the first The visual indicator liquid in the second chamber 4-5 and the second fluid channel can be the same liquid, such as red oil, the red oil should fill the second chamber 4-5, and the red oil is poured into the visualization scale 4- 7 half way up. When the cardiomyocytes adhering to the elastic membrane mature, they begin to beat, causing periodic deformation of the elastic membrane, causing the second chamber to expand or contract to drive the red visual indicator fluid to reciprocate in the second fluid channel , the intensity and frequency of cardiomyocyte beating can be directly determined by visualizing the intensity and frequency of the vibration of the indicator fluid in the second fluid channel.

The present invention directly measures the intensity and frequency of the beating of the cardiomyocytes by visualizing the intensity and frequency of the movement of the indicator fluid in the second fluid channel, that is, converting the beating of the cardiomyocytes into the reciprocating motion of the visual indicator fluid in the second fluid channel, so as to directly observe And measuring the overall beating intensity and frequency of all cardiomyocytes can reflect the overall beating state of all cells, greatly improving the efficiency and accuracy of cardiac drug evaluation.

The present invention can also integrate other organs, such as liver organs, so as to directly study the cardiotoxicity or efficacy of drug liver metabolites, and further, more other organs can be integrated to simulate the human body. To measure the cardiotoxicity or efficacy of a drug, the present invention finally provides a novel, highly biomimetic in vitro platform for cardiac drug screening.

Embodiment 2

Taking the preferred solution shown in FIG. 2 in the first embodiment as an example, the second embodiment of a detection method for simulating the beating intensity and frequency of myocardial cells using a heart chip provided by the present invention will be described below.

A detection method for simulating the beating intensity and frequency of cardiomyocytes using a heart chip (here refers to the heart chip in Embodiment 1), comprising the following steps:

S10, adding a cell culture solution to the first chamber 2-5 to culture heart-related cells, and adding a visual indicator solution to the second chamber 4-5 and the second fluid channel at the same time.

2, two passages (1-1, 2-1, 3 constitute one passage and 1-2, 2-2, 3) formed by the cover plate 1, the first substrate 2 and the elastic film Another channel is formed) into the first chambers 2-5, 2-6 and 2-8, respectively, adding cardiomyocyte culture medium, hepatocyte culture medium and adipocyte culture medium.

For example, please continue to refer to FIG. 2 , two passages (1-3, 2-3, 3-3, 4) formed by the cover plate 1, the first substrate 2, the elastic film, the second substrate 4 and the bottom plate 5 -3, 5 constitute one of the passages and 1-4, 2-4, 3-4, 4-4, 5 constitute the other passage) pour red oil into the second chamber 4-5 and the second fluid channel, The red oil should fill the second chamber 4-5, and the red oil should be filled to the half of the visual scale 4-7, then the through holes (1-3, 2-3, 3-3, 4-3, 5) Block it, leaving the openings of the through holes (1-4, 2-4, 3-4, 4-4, 5).

S20. After the cardiomyocytes adhered to the elastic membrane mature, the pulsation of the cardiomyocytes drives the elastic membrane to deform, so that the second chamber 4-5 expands or contracts, so as to drive the visual indicator fluid to reciprocate in the second fluid channel, The intensity and frequency of the cardiomyocyte beating are directly determined by visualizing the amplitude and frequency of the vibration of the indicator fluid in the second fluid channel, wherein the intensity and frequency of the cardiomyocyte beating are determined by a visual scale.

Embodiment 3

The third application embodiment of a heart chip provided by the present invention will be introduced below. The third embodiment is implemented based on the above-mentioned first and second embodiments, and is expanded to a certain extent on the basis of the first and second embodiments. .

This embodiment provides the application of the heart chip for culturing cardiomyocytes in vitro, and the specific structure of the heart chip, the marking of the through hole and the marking of the chamber are shown in FIG. 2 . The specific content of the heart chip in FIG. 2 has been described in detail in Embodiment 1, and details are not described here in this embodiment.

In this embodiment, as shown in FIG. 2 , a cell culture medium can be added to the first chambers 2-5 for culturing heart-related cells, for example, two cells consisting of a cover plate 1 , a first substrate 2 and an elastic membrane can be added. The channels (1-1, 2-1, 3 constitute one channel and 1-2, 2-2, 3 constitute another channel) add cardiomyocytes to the first chambers 2-5, 2-6 and 2-8, respectively Culture medium, hepatocyte culture medium and adipocyte culture medium.

Embodiment 4

The fourth embodiment of the application of a heart chip provided by the present invention will be introduced below. The fourth embodiment is implemented based on the third embodiment, and is expanded to a certain extent on the basis of the third embodiment.

This embodiment provides an application of a heart chip in simulating a heart organ and performing drug screening evaluation. The specific structure of the heart chip, the marking of the through hole and the marking of the chamber are shown in FIG. 2 . The specific content of the heart chip in FIG. 2 has been described in detail in Embodiment 1, and details are not described here in this embodiment.

In this embodiment, referring to FIG. 2 , two passages (1-1, 2-1, 3 constitute one passage and 1-2, 2- 2, 3 constitute another channel) respectively add cardiomyocyte culture fluid, hepatocyte culture fluid and adipocyte culture fluid to the first chamber 2-5, 2-6 and 2-8 for cell culture, and pass the cover plate. 1. Two passages (1-3, 2-3, 3-3, 4-3, 5 constitute one passage and 1-4, 2- 4, 3-4, 4-4, 5 constitute another passage) pour red oil into the second chamber 4-5 and the second fluid channel, the red oil should fill the second chamber 4-5, and the red The oil is poured to the 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) opening.

When the cardiomyocytes adhered to the elastic membrane mature, they start to beat, which causes the elastic membrane to undergo periodic deformation, so that the second chamber 4-5 expands or contracts, so as to drive the red visual indicator fluid in the second fluid channel Reciprocating motion, that is, the periodic expansion and contraction of the visual indicator fluid in the second fluid channel. By visualizing the rate and intensity of the expansion and contraction of the indicator fluid, the frequency and intensity of the cardiomyocyte beating can be intuitively judged.

First, the frequency and intensity of cardiomyocyte beats were recorded using a visual ruler (as shown in Figure 3), and electrophysiological signals were recorded using electrodes (3-5, 3-6) (as shown in Figure 5), and then evodiamine was passed through the pathway (The first through-hole 1-2, the second through-hole 2-2 and the channel formed by the elastic membrane) are added to the chip, and the evodiamine first flows through the fat cells in the first chamber 2-8, and after being metabolized by the fat, Then it flows through the three-dimensional cultured hepatocytes in the first chamber 2-6. After being metabolized by the hepatocytes, the metabolites and the original drug flow into the first chamber 2-5 to interact with the cardiomyocytes. After 24 hours, The frequency and intensity of cardiomyocyte beating (results shown in Figure 4), and electrophysiological signals (results shown in Figure 6) were then recorded.

From Figure 3 to Figure 6, it can be seen that after the cardiomyocytes interact with evodiamine and its metabolites, the beating frequency of cardiomyocytes becomes faster. The changes showed that evodiamine had certain cardiotoxicity.

Obviously, the above-mentioned embodiments are only examples for clear description, and are not intended to limit the implementation manner. For those of ordinary skill in the art, other different forms of changes or modifications can also be made on the basis of the above description. There is no need and cannot be exhaustive of all implementations here. However, the obvious changes or changes derived from this are still within the protection scope of the present invention.

Claims

A heart chip, characterized in that it comprises a cover plate, a first substrate, a second substrate and a bottom plate which are stacked in sequence, and an elastic layer is arranged between the first substrate and the second substrate;

The first substrate is provided with a first chamber for culturing cells;

The second base plate is provided with a second chamber and a second communication portion, the second communication portion is fitted with the bottom plate to form a second fluid channel, and the second fluid channel communicates with the second chamber, A visual indicator liquid is arranged in the second chamber and the second fluid channel;

The first chamber is connected to the second chamber through an elastic layer, and when the mature cardiomyocytes cultured in the first chamber are beating, the beating will drive the deformation of the elastic layer, so that the second chamber is expanded or contraction, to drive the visual indicator fluid to reciprocate in the second fluid channel, and the intensity and frequency of the cardiomyocyte beating can be directly determined by the amplitude and frequency of the visual indicator fluid vibrating in the second fluid channel.
The heart chip according to claim 1, wherein a first communication portion is further provided on the first substrate, and the first communication portion is bonded with the elastic layer to form a first fluid channel, and the first communication portion is A fluid channel connects the first chamber.
The cardiac chip according to claim 2, wherein the first communication portion is disposed on a side of the first substrate facing the elastic layer.
The heart chip according to claim 1, wherein the elastic layer is a deformable elastic film, and an adhesive layer is provided on the surface of the elastic film.
The heart chip according to claim 1 or 4, wherein the elastic layer is provided with electrodes, or electrodes are connected on the surface of heart-related cells.
The heart chip according to claim 1, further comprising a visualization scale, the visualization scale is disposed on the second substrate or the bottom plate, and the visualization scale is disposed close to the second fluid channel.
The heart chip according to claim 1, further comprising a through hole, the through hole is provided on the cover plate, the first substrate, the elastic layer, the second substrate and the bottom plate, the cover plate, the first substrate A substrate, the elastic layer, the second substrate and the bottom plate form a passage through the through hole.
A kind of detection method that uses heart chip as described in any one of claim 1-7 to simulate myocardial cell beat intensity and frequency, it is characterized in that, comprises the following steps:

adding a cell culture solution to the first chamber for cardiac-related cell culture, while adding a visual indicator solution to the second chamber and the second fluid channel;

After the cardiomyocytes adhered to the elastic layer mature, the pulsation of the cardiomyocytes drives the deformation of the elastic layer, so that the second chamber expands or contracts, so as to drive the visual indicator fluid to reciprocate in the second fluid channel, through Measuring the amplitude and frequency of the vibration of the visual indicator fluid within the second fluid channel directly determines the strength and frequency of the cardiomyocyte beating.
The detection method according to claim 8, wherein the intensity and frequency of the cardiomyocyte beating are determined by a visual scale.
An application of the heart chip according to any one of claims 1 to 7 in culturing cardiomyocytes in vitro, simulating a heart organ, and performing drug screening and evaluation.