CN217459447U - Skin chip - Google Patents

Abstract

The utility model relates to an organ chip technical field, concretely relates to skin chip. A skin chip comprising: the chip comprises a chip body and a chip body, wherein the chip body comprises a first chip, a second chip, a porous membrane and a third chip which are sequentially arranged, a first cavity is arranged on the second chip, a second cavity is arranged at the position of the third chip corresponding to the first cavity, and the first cavity and the second cavity are arranged in a through mode through the porous membrane; and the bubble removing film is arranged at the inlet of the second chamber between the second chip and the third chip so as to remove bubbles in the second chamber. The utility model provides a skin chip capable of removing bubbles.

Description

Skin chip

Technical Field

The utility model relates to an organ chip technical field, concretely relates to skin chip.

Background

Engineered skin can be used as a very valuable in vitro model to examine the permeability and inflammatory response of drugs in a high throughput manner. A typical approach for human skin engineering is to simplify the highly complex skin structure into two parts: epidermis and dermis.

In vitro 3D skin is stably fixed on the device and drugs and cosmetics can be added during the culture, the culture medium serving as a nutrient delivery pathway. Although conventional skin construction methods can construct a three-dimensional environment similar to skin cells in vivo, they are far from the true skin structure.

Organ chip technology enables researchers to design increasingly complex microenvironments, capture the structure and geometry of tissue, and better support organ-level functions. This technology is also currently being increasingly applied to dermal drug screening and cosmetic efficacy assessment, which seems to be the most advanced in vitro platform for drug safety and efficacy assessment. Despite advances in the construction and study of in vitro simulated organs, successful application of microfluidic chips in skin pathology studies and drug screening is still lacking.

Although a bionic system of a skin microenvironment can be simulated by adopting a microfluidic chip, the formation of a gas-liquid interface is influenced because a culture medium has bubbles, so that the effectiveness of screening cosmetics and medicines is influenced.

SUMMERY OF THE UTILITY MODEL

Therefore, the to-be-solved technical problem of the utility model lies in overcoming among the prior art and having the bubble entering culture chamber because of the culture medium to influence the validity of cosmetics and drug screening, thereby provide a skin chip that can get rid of the bubble.

In order to solve the technical problem, the utility model provides a skin chip, include:

the chip comprises a chip body and a chip cover, wherein the chip body comprises a first chip, a second chip, a porous membrane and a third chip which are sequentially arranged, a first cavity is arranged on the second chip, a second cavity is arranged at the position of the third chip, which corresponds to the first cavity, and the first cavity and the second cavity are arranged in a run-through manner through the porous membrane;

and the bubble removing film is arranged at the inlet of the second chamber between the second chip and the third chip so as to remove bubbles in the second chamber.

Optionally, a pair of medium inlets and medium outlets are formed in the first chip, a first through hole and a second through hole which are communicated with the medium inlets and the medium outlets are respectively formed in corresponding positions of the second chip, the first through hole and the second through hole are both communicated with the second chamber, and the defoaming film is arranged between the first through hole and the inlets of the second chamber.

Optionally, a pair of second flow channels communicated with the second chamber is further disposed on the third chip, and the defoaming film is disposed between the first through hole and an inlet of the corresponding second flow channel.

Optionally, the de-bubbling membrane is made of polytetrafluoroethylene.

Optionally, the second chip is further provided with a pair of first flow channels communicated with the first chamber, and the first chip is provided with a gas inlet and a gas outlet respectively communicated with the pair of first flow channels.

Optionally, the first chip is made of a transparent material.

Optionally, the porous membrane is slightly larger in size than the second chamber.

The utility model discloses technical scheme has following advantage:

1. the utility model provides a skin chip, including the chip body, the chip body is including the first chip that sets gradually, the second chip, porous membrane and third chip, be equipped with first cavity on the second chip, the third chip is provided with the second cavity with first cavity correspondence, the first cavity and the second cavity that correspond to set up are favorable to complete skin tissue lower floor and culture medium to contact completely, make the better infiltration of culture medium advance skin tissue, do benefit to the cultivation of skin tissue, first cavity and second cavity pass through the porous membrane and link up the setting, the culture medium passes through the porous membrane and gets into the second cavity, the metabolite permeable porous membrane that the metabolism produced gets into the second cavity and is taken away in the skin tissue culture process, the metabolite of real time monitoring skin tissue, thereby monitor the influence of different concentration gradient medicines to skin tissue; the entrance of the second chamber between second chip and the third chip is located to the bubble removal membrane, and when the culture medium passed through the membrane hole that removes the bubble, the tension of bubble in the culture medium had been eliminated to the shearing force that forms for the bubble splitting is filtered, thereby gets rid of the bubble when culture medium got into the second chamber, does not influence the formation of gas-liquid interface, makes the culture medium get into the second chamber smoothly, with the influence that reduces tissue culture.

2. The utility model provides a skin chip is equipped with a pair of first runner with first cavity intercommunication on the second chip, goes into second cavity top with the air pump during the experiment from the gas inlet pump of first chip with sterile air, flows through first runner, and human skin microenvironment can be simulated to first runner, and the skin tissue that the external preparation of gas-liquid is favorable to is cultivateed mutually forms stratum corneum and basement membrane.

3. The utility model provides a skin chip, first chip are transparent material, are favorable to surveing the tissue form change in real time.

4. The utility model provides a skin chip, first chip seal the chip cavity at the cultivation in-process, can reveal after the cultivation and form open cultivation cavity, chemical toxicity and drug test can directly add to on the skin tissue to simulation percutaneous medication, or from medium entry simulation intravenous route medication of dosing, the mode of dosing is various, is favorable to accurate testing result.

Drawings

In order to more clearly illustrate the embodiments of the present invention or the technical solutions in the prior art, the drawings used in the embodiments or the technical solutions in the prior art will be briefly described below, and it is obvious that the drawings in the following description are some embodiments of the present invention, and for those skilled in the art, other drawings can be obtained according to these drawings without creative efforts.

Fig. 1 is a schematic structural diagram of a skin chip.

Description of reference numerals:

1-a media inlet; 2-a gas inlet; 3-a gas outlet; 4-a media outlet; 5-a first flow channel; 6-a second flow channel; 7-a second chamber; 8-porous membrane; 9-a first chamber; 10-a first chip; 11-a second chip; 12-a third chip; 13-a second via; 14-a first via; and 15-removing the bubble film.

Detailed Description

The technical solution of the present invention will be described clearly and completely with reference to the accompanying drawings, and obviously, the described embodiments are some, but not all embodiments of the present invention. Based on the embodiments in the present invention, all other embodiments obtained by a person skilled in the art without creative work belong to the protection scope of the present invention.

In the description of the present invention, it should be noted that the terms "center", "upper", "lower", "left", "right", "vertical", "horizontal", "inner", "outer", and the like indicate orientations or positional relationships based on the orientations or positional relationships shown in the drawings, and are only for convenience of description and simplification of description, but do not indicate or imply that the device or element referred to must have a specific orientation, be constructed and operated in a specific orientation, and thus, should not be construed as limiting the present invention. Furthermore, the terms "first," "second," and "third" are used for descriptive purposes only and are not to be construed as indicating or implying relative importance.

In the description of the present invention, it is to be noted that, unless otherwise explicitly specified or limited, the terms "mounted," "connected," and "connected" are to be construed broadly, and may be, for example, fixedly connected, detachably connected, or integrally connected; can be mechanically or electrically connected; they may be connected directly or indirectly through intervening media, or they may be interconnected between two elements. The specific meaning of the above terms in the present invention can be understood in specific cases to those skilled in the art.

Furthermore, the technical features mentioned in the different embodiments of the invention described below can be combined with each other as long as they do not conflict with each other.

As shown in figure 1, the skin chip is used for bionic manufacture of skin models of true epidermis and basement membrane, and comprises a chip body and a defoaming membrane 15, wherein the thickness of the whole chip is less than 7 mm.

The chip body is including the first chip 10 that sets gradually, the second chip 11, porous membrane 8 and third chip 12, for observing the change of tissue morphology in real time, first chip 10 adopts transparent material, be equipped with first cavity 9 on the second chip 11, first cavity 9 is for cultivateing the chamber, be equipped with second cavity 7 on the third chip 12, second cavity 7 is the culture solution pond, second cavity 7 corresponds the setting with first cavity 9, and first cavity 9 and second cavity 7 link up the setting through porous membrane 8, porous membrane 8's size slightly is greater than second cavity 7's size. The first chip 10 is provided with a pair of medium inlets 1 and medium outlets 4, and is further provided with a pair of gas inlets 2 and gas outlets 3, the pair of medium inlets 1 and medium outlets 4 and the pair of gas inlets 2 and gas outlets 3 are coaxially arranged, the second chip 11 is provided with a first through hole 14 and a second through hole 13 corresponding to the pair of medium inlets 1 and medium outlets 4, the first through hole 14 and the second through hole 13 are both communicated with the second chamber 7 but not communicated with the first chamber 9, the second chip 11 is further provided with a pair of first runners 5 communicated with the first chamber 9, inlets and outlets of the first runners 5 are respectively communicated with the gas inlets 2 and the gas outlets 3, the third chip 12 is further provided with a pair of second runners 6 communicated with the second chamber 7, and inlets and outlets of the second runners 6 are respectively communicated with the first through holes 14 and the second through holes 13.

Remove bubble membrane 15 and locate between the entry of first through-hole 14 and corresponding second runner 6, the diameter is 4mm, adopt the polytetrafluoroethylene material, when the culture medium passed through bubble membrane 15, the tension of bubble in the culture medium has been eliminated to the shearing force that forms for the bubble splitting is filtered, and the bubble in the culture medium can be got rid of, thereby does not influence the formation at gas-liquid interface, makes the culture medium get into second chamber 7 smoothly, has reduced the influence to tissue culture.

In order to obtain a skin chip mold, a 3D printing method is adopted to obtain a silicon plate with the same structure as the first flow channel 5 and the first cavity 9 in the figure 1, monomers and a curing agent are mixed and stirred uniformly, the mixture is poured into the mold, bubbles generated after stirring are extracted through a vacuum pump, the mixed solution after removing the bubbles is poured into the silicon plate, the silicon plate is placed on a heating plate to be cured at the temperature of 80 ℃ for 1 hour, PDMS solid is formed, the cured PDMS is stripped from the silicon plate, holes are punched at positions corresponding to the first through hole 14 and the second through hole 13, then the porous membrane 8 and the bubble removing membrane 15 are respectively clamped at corresponding positions and attached, the mold is placed on the heating plate again for 1 hour at the temperature of 80 ℃, and a weight of 1Kg is placed above the mold to ensure sealing.

When the skin chip is used, a fibroblast suspension with a certain concentration and matrigel are added into a first chamber 9, a tissue layer structure with a certain thickness is formed after the first chamber 9 is cultured to be gelatinized, then a peristaltic pump is adopted to continuously focus on a culture medium, a certain proportion of keratinocytes and melanocytes are injected above the tissue layer after a period of culture, gas-liquid perfusion is carried out after a period of culture, gas-liquid interface culture is realized, whole skin cell culture is realized, then a first chip 10 is covered, the first chip 10, a second chip 11, a porous membrane 8 and a third chip 12 are installed together by screws, sterile air is pumped into the upper part of the first chamber 9 from a gas inlet 2 of the first chip 10 by an air pump, flows through a first flow passage 5 above and is discharged from a gas outlet 3, the culture medium enters from a medium inlet 1, bubbles are removed through a bubble removing membrane 15 and then flows through a second flow passage 6 of the third chip 12, and the skin tissue enters the second chamber 7 through the porous membrane 8, meanwhile, metabolic products generated by metabolism in the skin tissue culture process enter the second flow channel 6 through the porous membrane 8 and are taken away, finally, the culture medium is discharged from the medium outlet 4, the construction and culture of the whole skin tissue are carried out through the designed skin chip, the sterile gas and the culture medium both flow dynamically, a bionic microenvironment can be provided, the skin tissue is cultured in a gas-liquid interface environment, corresponding shearing force is provided, and the stratum corneum of the skin tissue and the substrate film formation of a dermal epidermis interface are facilitated.

As an alternative embodiment, the de-bubbling film 15 may also be made of polyethylene terephthalate, and may have other shapes capable of completely covering the first through hole 14.

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 can be made without departing from the scope of the invention.

Claims (7)

1. A skin chip, comprising:

the chip comprises a chip body and a chip body, wherein the chip body comprises a first chip (10), a second chip (11), a porous membrane (8) and a third chip (12) which are sequentially arranged, a first cavity (9) is arranged on the second chip (11), a second cavity (7) is arranged at the position, corresponding to the first cavity (9), of the third chip (12), and the first cavity (9) and the second cavity (7) are arranged in a penetrating manner through the porous membrane (8);

a de-bubbling film (15) disposed at an inlet of the second chamber (7) between the second chip (11) and the third chip (12) to remove bubbles in the second chamber (7).

2. The dermal chip of claim 1, wherein the first chip (10) is provided with a pair of a medium inlet (1) and a medium outlet (4), the second chip (11) is provided at a corresponding position with a first through hole (14) and a second through hole (13) respectively communicating with the medium inlet (1) and the medium outlet (4), the first through hole (14) and the second through hole (13) are both communicated with the second chamber (7), and the de-bubbling membrane (15) is arranged between the first through hole (14) and the inlet of the second chamber (7).

3. The dermal chip of claim 2, characterized in that the third chip (12) is further provided with a pair of second flow channels (6) communicating with the second chamber (7), the de-bubbling membrane (15) being provided between the first through-hole (14) and the inlet of the respective second flow channel (6).

4. A skin chip according to any one of claims 1 to 3, characterized in that said de-bubbling membrane (15) is of teflon.

5. A dermal chip according to any of claims 1 to 3, characterized in that the second chip (11) is further provided with a pair of first channels (5) communicating with the first chamber (9), and the first chip (10) is provided with a gas inlet (2) and a gas outlet (3) respectively communicating with the pair of first channels (5).

6. A skin chip according to any one of claims 1 to 3, characterized in that said first chip (10) is of transparent material.

7. A skin chip according to any one of claims 1 to 3, characterized in that the size of the porous membrane (8) is slightly larger than the size of the second chamber (7).

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