CN110305787A - An in vivo mechanical environment simulation device - Google Patents

Abstract

The present invention provides a device for simulating the mechanical environment in vivo, comprising: a cell culture medium storage chamber for storing cell culture medium; a cell culture device with a medium inlet and a medium outlet; the medium inlet passes through a The peristaltic pump is fluidly connected to the cell culture medium storage chamber, and the medium outlet is fluidly connected to the cell culture medium storage chamber to form a circulation path; wherein, a piezoelectric ceramic sheet is arranged in the cell culture device, and the The piezoelectric ceramic sheet is conductively connected with a signal generating device, and the amplitude and frequency of the piezoelectric ceramic sheet are controlled by the signal generating device.

Description

An in vivo mechanical environment simulation device

technical field

The invention relates to the field of cell culture, in particular to an in vivo mechanical environment simulation device for cell culture.

Background technique

In cell culture, the stressed state of cells is very important for culturing tissues in vitro. It is currently believed that tissues in organisms such as bone and joints are subject to alternating positive pressure and shear force when body fluid flows. Almost all tubular systems, such as: arteries, In systems such as veins, there are two kinds of forces.

Traditional microfluidic mechanical environment design usually simulates unidirectional normal stress by exerting pressure on cells through elastic membranes, which cannot control the frequency of stress, and cannot quantitatively study the impact of cell stress on cell growth and differentiation.

Therefore, a new in vivo mechanical environment simulator is needed to solve the above problems.

Contents of the invention

An object of the present invention is to provide a device for simulating the mechanical environment in the body. By controlling the amplitude and frequency of the piezoelectric ceramic sheet, a force similar to that in the human body is generated in the flow channel of the cell culture device, so that the cells can move faster and better. Growth and survival in the cytosol.

In order to solve the above problems, the present invention provides a device for simulating the mechanical environment in vivo, comprising: a cell culture medium storage chamber for storing cell culture medium; a cell culture device with a culture medium inlet and a culture medium outlet; The medium inlet is fluidly connected to the cell culture medium storage cavity through a peristaltic pump, and the medium outlet is fluidly connected to the cell culture medium storage cavity to form a circulation path; wherein, a piezoelectric A ceramic sheet, the piezoelectric ceramic sheet is conductively connected with a signal generating device, and the amplitude and frequency of the piezoelectric ceramic sheet are controlled by the signal generating device.

Those skilled in the art can understand that the piezoelectric ceramic sheet and the signal generating device are commercially available products known in the art.

In one embodiment of the present invention, the cell culture device includes: an upper substrate and a lower substrate oppositely arranged, and a microfluidic chip, and the microfluidic chip is sandwiched between the upper substrate and the lower substrate Between; wherein, the piezoelectric ceramic sheet is fixedly arranged on the lower substrate, so that the piezoelectric ceramic sheet is in contact with the micro-channel chip.

In an embodiment of the present invention, the micro-channel chip includes: a micro-channel structure plate, a concave micro-channel structure is formed on the micro-channel structure plate, and the micro-channel structure has a fluid The input end and a fluid output end; and, an upper cover plate, the upper cover plate is covered on the micro-channel structure plate, and the upper cover plate is corresponding to the fluid input end and the said upper cover plate The fluid output ends respectively have a through hole to form the medium inlet and the medium outlet of the cell culture device.

Those skilled in the art can understand that the micro-channel structure can be designed and shaped according to actual needs.

In an embodiment of the present invention, at least one strain gauge is fixedly arranged on the lower substrate, and the strain gauge is arranged in the micro-channel chip. Those skilled in the art can understand that the strain gauges are commercially available products known in the art.

In an embodiment of the present invention, the upper base plate and the lower base plate are fixedly connected by bolts.

In an embodiment of the present invention, the medium inlet is fluidly connected to the peristaltic pump through a polyethylene tube, and the peristaltic pump is fluidly connected to the cell culture medium storage cavity through a polyethylene tube, and the medium The outlet is fluidly connected to the cell culture medium storage chamber through polyethylene tubing.

In an embodiment of the present invention, the strain gauge is electrically connected to a data analysis device for receiving and processing the measurement data of the strain gauge.

In an embodiment of the present invention, the data analysis device is a data acquisition card.

In the in vivo mechanical environment simulation device of the present invention, the microfluidic chip is used as a cell culture system, and by controlling the amplitude and frequency of the piezoelectric ceramic strain gauge to apply appropriate shear force and normal stress to the cells, to achieve Simulate the fluid flow and force in the human body cavity. At the same time, the shear force and normal stress actually received by the cell culture device are detected in real time through the strain gauges, so as to be adjusted. Therefore, the in vivo mechanical environment simulating device of the present invention creates a more favorable environment for cell growth, and provides a basis for the further development of cell research.

Compared with the prior art, the present invention has the following beneficial effects:

1. The in vivo mechanical environment simulation device of the present invention has the characteristics of small device, small dose, and sensitive response;

2. The mechanical environment simulation device in the body described in the invention can quantify the mechanical analog quantity through the magnitude of the voltage, and has the characteristics of accurate simulation data, fine adjustable interval, and large adjustment range;

3. The voltage frequency of the piezoelectric ceramic sheet in the in vivo mechanical environment simulation device described in the invention is adjustable, giving the possibility of measurement under different pulsating environments;

4. Compared with the traditional static culture, the device for simulating the mechanical environment in the body of the present invention has the advantages of more realistic culture environment, controllable flow rate and controllable mechanical conditions;

5. Compared with the traditional negative pressure dynamic culture, the in vivo mechanical environment simulation device of the present invention has the advantages of simpler structure, convenient operation, and semi-automatic control of mechanical simulation.

Description of drawings

FIG. 1 is a schematic structural diagram of an in vivo mechanical environment simulation device according to an embodiment of the present invention;

Fig. 2 is an exploded view of the cell culture device of the in vivo mechanical environment simulation device.

Detailed ways

The following describes the preferred embodiments of the present invention with reference to the accompanying drawings to prove that the present invention can be implemented. The embodiments can fully introduce the present invention to those skilled in the art, making its technical content clearer and easier to understand. The present invention can be embodied in many different forms of embodiments, and the protection scope of the present invention is not limited to the embodiments mentioned herein.

As shown in FIG. 1 , the present invention provides an in vivo mechanical environment simulation device 100 , including: a cell culture medium storage chamber 200 , a cell culture device 300 and a peristaltic pump 400 . As shown in the figure, the cell culture medium storage chamber 200, the cell culture device 300 and the peristaltic pump 400 form a circulation path through a polyethylene tube, so that the cell culture medium storage chamber is driven by the peristaltic pump 400 The cell culture medium within 200 flows in the circulation channel.

The structure of the cell culture device 300 will be described in detail below with reference to FIG. 2 .

As shown in FIG. 2 , the cell culture device 300 includes an upper substrate 310 , a lower substrate 320 , and a microfluidic chip 330 sandwiched between the upper substrate 310 and the lower substrate 320 . The piezoelectric ceramic sheet 321 is fixedly arranged on the lower substrate 320 , so that the piezoelectric ceramic sheet 321 is in contact with the micro-channel chip 330 . The piezoelectric ceramic sheet 321 is conductively connected with a signal generating device 340 , and the amplitude and frequency of the piezoelectric ceramic sheet 321 are controlled by the signal generating device 340 . Both the piezoelectric ceramic sheet 321 and the signal generating device 340 are commercially available products known in the art.

As shown in Figure 2, the micro-channel chip 330 includes: a micro-channel structure plate 331 and an upper cover plate 332, a concave micro-channel structure is formed on the micro-channel structure plate 331, and the micro-channel structure The upper cover plate 332 covers the micro-channel structure plate 331 to form an inner cavity of the micro-channel structure.

Those skilled in the art can understand that the micro-channel structure of the micro-channel chip 330 can be designed and shaped according to actual needs. In this embodiment, the micro-channel chip 330 is in the form of constitute, but are not limited to.

As shown in Figure 2, the microfluidic channel structure is a stepped cylindrical cavity, including: a first cylindrical cavity 333, a second cylindrical cavity 334, a cell scaffold cavity 335, a first cylindrical cavity Four cylindrical cavities 336 and a fifth cylindrical cavity 337 . Wherein, the first cylindrical cavity 333 and the fifth cylindrical cavity 337 are 10 mm long and 4 mm in diameter. The second cylindrical cavity 334 and the fourth cylindrical cavity 336 are 5.5 mm long and 5 mm in diameter. The cell scaffold cavity 335 is 14.5 mm long and 6.5 mm in diameter.

The micro-channel structure has been formed in any known way, for example, the designed flow channel is presented on a glass slide with abs material and shadowless glue, fixed by ultraviolet light, and then made with a ratio of 10:1 The PDMS material is poured on it, and the air bubbles in the PDMS material are drawn out by using a vacuum pump, and finally heated on a heating table to solidify and form.

As shown in FIG. 2 , the upper cover plate has two through holes, through which the medium inlet 301 and the medium outlet 302 of the cell culture device 300 are respectively inserted.

As shown in FIG. 2 , a strain gauge (not labeled in the figure) can be arranged in the micro-channel structure of the micro-channel chip 330 to detect the actual stress of the micro-channel chip 330 . As shown in Figure 1, the strain gauge can be electrically connected with a data analysis device 500 such as a data acquisition card for receiving and processing the measurement data of the strain gauge, and can be further connected with a computer 600 for displaying Analyze and store measurement data.

In the in vivo mechanical environment simulation device of the present invention, the microfluidic chip is used as a cell culture system, and by controlling the amplitude and frequency of the piezoelectric ceramic strain gauge to apply appropriate shear force and normal stress to the cells, to achieve Simulate the fluid flow and force in the human body cavity. At the same time, the shear force and normal stress actually received by the cell culture device are detected in real time through the strain gauges, so as to be adjusted. Therefore, the in vivo mechanical environment simulating device of the present invention creates a more favorable environment for cell growth, and provides a basis for the further development of cell research.

The above is only a preferred embodiment of the present invention, it should be pointed out that for those of ordinary skill in the art, without departing from the principle of the present invention, some improvements and modifications can also be made, and these improvements and modifications should also be considered Be the protection scope of the present invention.

Claims (8)

1. An in vivo mechanical environment simulation device, comprising:

a cell culture medium storage chamber for storing cell culture medium;

a cell culture device having a medium inlet and a medium outlet; the culture medium inlet is in fluid connection with the cell culture medium storage cavity through a peristaltic pump, and the culture medium outlet is in fluid connection with the cell culture medium storage cavity to form a circulation channel; wherein,

the cell culture device is internally provided with a piezoelectric ceramic piece, the piezoelectric ceramic piece is electrically connected with a signal generating device, and the amplitude and the frequency of the piezoelectric ceramic piece are controlled by the signal generating device.

2. The simulation apparatus of claim 1, wherein the cell culture apparatus comprises:

an upper substrate and a lower substrate disposed opposite to each other, and,

the micro-channel chip is clamped between the upper substrate and the lower substrate; wherein,

the piezoelectric ceramic piece is fixedly arranged on the lower substrate, so that the piezoelectric ceramic piece is in contact with the micro-channel chip.

3. The simulation apparatus according to claim 2, wherein the micro flow channel chip comprises:

the micro-channel structure plate is provided with an inwards concave micro-channel structure, and the micro-channel structure is provided with a fluid input end and a fluid output end; and the number of the first and second groups,

and the upper cover plate covers the micro-channel structure plate, and is provided with a through hole corresponding to the fluid input end and the fluid output end respectively so as to form the culture medium inlet and the culture medium outlet of the cell culture device.

4. The simulation device of claim 3, wherein at least one strain gauge is further fixed on the lower substrate, and the strain gauge is disposed in the micro flow channel chip.

5. The simulation apparatus of claim 3, wherein the upper substrate and the lower substrate are fixedly connected by a bolt.

6. The simulation apparatus of claim 3, wherein the medium inlet is fluidly connected to the peristaltic pump by a polyethylene tube, the peristaltic pump is fluidly connected to the cell medium storage chamber by a polyethylene tube, and the medium outlet is fluidly connected to the cell medium storage chamber by a polyethylene tube.

7. The simulation apparatus of claim 4, wherein the strain gage is conductively coupled to a data analysis device for receiving and processing measurement data from the strain gage.

8. The simulation apparatus of claim 7, wherein the data analysis apparatus is a data acquisition card.