CN109517739A - Double organs are coupled three-layer laminated integrated chip - Google Patents

Double organs are coupled three-layer laminated integrated chip Download PDF

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Publication number
CN109517739A
CN109517739A CN201811609624.8A CN201811609624A CN109517739A CN 109517739 A CN109517739 A CN 109517739A CN 201811609624 A CN201811609624 A CN 201811609624A CN 109517739 A CN109517739 A CN 109517739A
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silicone polymer
dimethyl silicone
culture
polymer layer
organs
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田甜
李弦
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Chongqing University
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Chongqing University
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    • CCHEMISTRY; METALLURGY
    • 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
    • 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
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61HPHYSICAL THERAPY APPARATUS, e.g. DEVICES FOR LOCATING OR STIMULATING REFLEX POINTS IN THE BODY; ARTIFICIAL RESPIRATION; MASSAGE; BATHING DEVICES FOR SPECIAL THERAPEUTIC OR HYGIENIC PURPOSES OR SPECIFIC PARTS OF THE BODY
    • A61H1/00Apparatus for passive exercising; Vibrating apparatus; Chiropractic devices, e.g. body impacting devices, external devices for briefly extending or aligning unbroken bones
    • A61H1/02Stretching or bending or torsioning apparatus for exercising
    • A61H1/0237Stretching or bending or torsioning apparatus for exercising for the lower limbs
    • A61H1/0266Foot
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61HPHYSICAL THERAPY APPARATUS, e.g. DEVICES FOR LOCATING OR STIMULATING REFLEX POINTS IN THE BODY; ARTIFICIAL RESPIRATION; MASSAGE; BATHING DEVICES FOR SPECIAL THERAPEUTIC OR HYGIENIC PURPOSES OR SPECIFIC PARTS OF THE BODY
    • A61H9/00Pneumatic or hydraulic massage
    • A61H9/005Pneumatic massage
    • A61H9/0078Pneumatic massage with intermittent or alternately inflated bladders or cuffs
    • AHUMAN NECESSITIES
    • A63SPORTS; GAMES; AMUSEMENTS
    • A63BAPPARATUS FOR PHYSICAL TRAINING, GYMNASTICS, SWIMMING, CLIMBING, OR FENCING; BALL GAMES; TRAINING EQUIPMENT
    • A63B23/00Exercising apparatus specially adapted for particular parts of the body
    • A63B23/035Exercising apparatus specially adapted for particular parts of the body for limbs, i.e. upper or lower limbs, e.g. simultaneously
    • A63B23/04Exercising apparatus specially adapted for particular parts of the body for limbs, i.e. upper or lower limbs, e.g. simultaneously for lower limbs
    • A63B23/08Exercising apparatus specially adapted for particular parts of the body for limbs, i.e. upper or lower limbs, e.g. simultaneously for lower limbs for ankle joints
    • CCHEMISTRY; METALLURGY
    • 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
    • C12M23/00Constructional details, e.g. recesses, hinges
    • C12M23/34Internal compartments or partitions
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61HPHYSICAL THERAPY APPARATUS, e.g. DEVICES FOR LOCATING OR STIMULATING REFLEX POINTS IN THE BODY; ARTIFICIAL RESPIRATION; MASSAGE; BATHING DEVICES FOR SPECIAL THERAPEUTIC OR HYGIENIC PURPOSES OR SPECIFIC PARTS OF THE BODY
    • A61H2201/00Characteristics of apparatus not provided for in the preceding codes
    • A61H2201/16Physical interface with patient
    • A61H2201/1602Physical interface with patient kind of interface, e.g. head rest, knee support or lumbar support
    • A61H2201/164Feet or leg, e.g. pedal
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61HPHYSICAL THERAPY APPARATUS, e.g. DEVICES FOR LOCATING OR STIMULATING REFLEX POINTS IN THE BODY; ARTIFICIAL RESPIRATION; MASSAGE; BATHING DEVICES FOR SPECIAL THERAPEUTIC OR HYGIENIC PURPOSES OR SPECIFIC PARTS OF THE BODY
    • A61H2205/00Devices for specific parts of the body
    • A61H2205/12Feet

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  • Life Sciences & Earth Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • General Health & Medical Sciences (AREA)
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  • Bioinformatics & Cheminformatics (AREA)
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  • Biomedical Technology (AREA)
  • Orthopedic Medicine & Surgery (AREA)
  • Physical Education & Sports Medicine (AREA)
  • Genetics & Genomics (AREA)
  • General Engineering & Computer Science (AREA)
  • Pain & Pain Management (AREA)
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  • Biochemistry (AREA)
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Abstract

The invention discloses a kind of double organs to be coupled three-layer laminated integrated chip, including the first polymethyl methacrylate layers, the first dimethyl silicone polymer layer, the second dimethyl silicone polymer layer and the second polymethyl methacrylate layers from top to bottom set gradually, it is spaced apart and is set there are two miniature culture pond on the binding face of the first dimethyl silicone polymer layer and the second dimethyl silicone polymer layer, each culture pond is provided with the inlet tube and outlet extended in culture pond by the first polymethyl methacrylate layers upper surface.The present invention is spaced apart the cell set there are two two kinds of Different Organs of culture pond culture on the binding face of the first dimethyl silicone polymer layer and the second dimethyl silicone polymer layer, according to the Quality Design culture solution type and flow velocity of micro-organs, micro-organs cell morphology and survival rate, and the content of quantitative analysis each group organ biomarker can directly be observed.

Description

Double organs are coupled three-layer laminated integrated chip
Technical field
The invention belongs to cultivate organ chip field, more particularly to a kind of double three-layer laminated integrated cores of organ coupling Piece.
Background technique
The scientist headed by WYSS research institute, Harvard University proposes the concept of organ chip in recent years, it would be desirable to enough Microchip replicates the function of human organ, even replaces controversial zoopery to reduce in drug development process, Clinical Transformation Application is set to become the more easy idealization diagnosis ex vivo that can also be achieved disease.Organ chip is by calculator memory The transparent flexible polymer of size is constituted, and inside is hollow microfluidic channel, the human cell of channel liner work.Study people Member goes out the physiology and mechanical function of human organ by design simulation, observes the response situation of cell in real time in drug test. The chip developed includes lung, heart, liver, kidney, blood vessel and marrow etc..
Scientist in clinical precisely diagnosis and accurate therapeutic process using more predictability, more effective means for being come The exploration for carrying out Disease Warning Mechanism and effective and safe medication never stopped.Mainly carried out at present using experimental animal and cell model The research of above-mentioned problem in science.However, the nonuniformity and autoblast model microenvironment of human body and animal epigenetic without Method simulation target is organotropic in body state, while the limitation of ethics, these are all that disease diagnosis and therapy research instantly is difficult to The realistic problem and challenge of avoidance seriously constrain our scientific knowledges to human diseases, are badly in need of the appearance of new model.
To solve this problem, the organ that can only be implanted into single type in the single organ chip developed at present mostly is thin Born of the same parents, and really life process is multiple organ synergistic effects as a result, therefore, ideal way is by various organ chipsets It is merged the manikin for connecing one micromation of building, helps us understand and recognize the physiology and pathologic process of human body.In human body It is different with the active function micro-organs biochemical parameter of physiological metabolism.And during body metabolism and drug test, often It often needs while monitoring the double organ metabolic conditions connected each other as a whole.Therefore, how according to reflection Human Physiology dissection The physiology pharmacokinetic model (physiologically based pharmacokinetics, PBPK) of structure establishes more devices Official is coupled chip, the dynamic change of more preferable simulation human body generated metabolite when being changed by outside stimulus or internal gene Change, becomes the emphasis of those skilled in the art's research.
Summary of the invention
It is an object of the invention to provide a kind of double organs to be coupled three-layer laminated integrated chip, can be fully solved above-mentioned existing There is the shortcoming of technology.
The purpose of the present invention is realized by following technical proposals:
The three-layer laminated integrated chip of a kind of double organ couplings, including the first polymethyl from top to bottom set gradually Sour methyl esters layer, the first dimethyl silicone polymer layer, the second dimethyl silicone polymer layer and the second polymethyl methacrylate layers, institute It states to be spaced apart on the binding face of the first dimethyl silicone polymer layer and the second dimethyl silicone polymer layer and set there are two culture pond, often A culture pond is provided with the inlet tube and outlet extended in culture pond by the first polymethyl methacrylate layers upper surface.
Preferably, the inlet tube extends to the left bottom of culture pond, the outlet extends to the right side of culture pond Lateral roof.
Preferably, being arranged in the second polymethyl methacrylate layers, there are two the circular holes that diameter is 16mm-18mm, each One culture pond of circular hole face is easy to use two culture ponds of micro- sem observation by circular hole.
Preferably, each culture pond includes the first culture for being opened in the first dimethyl silicone polymer layer lower surface Slot and the second culture tank for being opened in the second dimethyl silicone polymer layer upper surface, first culture tank are overlapped in the second culture Slot upper surface.
Preferably, first culture tank and the second culture tank are cylindrical structure, it is highly 1mm-2mm, diameter is 10mm-12mm。
Compared with prior art, the beneficial effects of the present invention are:
The configuration of the present invention is simple, design is reasonable, in the first dimethyl silicone polymer layer and the second dimethyl silicone polymer layer Binding face on be spaced apart the cell set there are two two kinds of Different Organs of culture pond culture, according to the Quality Design culture of micro-organs Flow velocity can directly observe micro-organs cell morphology and survival rate, the content of quantitative analysis each group organ biomarker.
Detailed description of the invention
Fig. 1 is longitudinal section view of the invention;
Fig. 2 is exploded view of the invention.
Appended drawing reference: the first polymethyl methacrylate layers of 1-, 2- the first dimethyl silicone polymer layer, the poly- diformazan of 3- second Radical siloxane layer, the second polymethyl methacrylate layers of 4-, the first screw of 5-, the first lock nut of 6-, the second screw of 7-, 8- Two lock nuts, the first culture tank of 9-, the second culture tank of 10-, 11- inlet tube, 12- outlet, 13- circular hole, 14- third spiral shell Nail, 15- third lock nut.
Specific embodiment
The present invention is further illustrated with attached drawing combined with specific embodiments below.
As shown in Figure 1 to Figure 2, a kind of double organs are coupled three-layer laminated integrated chip, including are from top to bottom successively bonded The first polymethyl methacrylate layers 1, the first dimethyl silicone polymer layer 2, the second dimethyl silicone polymer layer 3 and second poly- The length of methyl methacrylate layer 4, the first dimethyl silicone polymer layer 2 and the second dimethyl silicone polymer layer 3 is 75mm- 80mm, width are 25mm-30mm, are highly 4mm-6mm, the first polymethyl methacrylate layers 1 and the second poly- methyl-prop The length of e pioic acid methyl ester layer 4 is 86mm-90mm, and width is 35mm-40mm, is highly 3mm-5mm, the first poly- methyl-prop The left and right ends of e pioic acid methyl ester layer 1 and the left and right ends of the second polymethyl methacrylate layers 4 offer threaded hole, use One screw 5 is threadedly coupled the left end of the first polymethyl methacrylate layers 1 and the left end of the second polymethyl methacrylate layers 4, And locked with the first lock nut 6, the right end and the of the first polymethyl methacrylate layers 1 is threadedly coupled using the second screw 7 The right end of two polymethyl methacrylate layers 4, and locked with the second lock nut 8, similarly, in the first polymethyl methacrylate The front of and behind of layer 1 and the second polymethyl methacrylate layers 4 is solid by third screw 14 and the locking of third lock nut 15 Fixed first polymethyl methacrylate layers 1 and the second polymethyl methacrylate layers 4, four layer materials of such chip pass through screw It fits and is fixed together, form closed double organ chip sets, be similar to sandwich sandwich structure, the first polydimethylsiloxanes Culture pond there are two setting, the second poly-methyl methacrylate are spaced apart on the binding face of alkane layer 2 and the second dimethyl silicone polymer layer 3 The circular hole 13 that diameter is 16mm-18mm is provided in ester layer 4, each 13 face of circular hole culture pond one by one can not beaten in this way Microscope direct observing micro-organs upgrowth situation in the case where minisize reaction pond is opened, each culture pond includes being opened in first poly- two First culture tank 9 of 2 lower surface of methylsiloxane layer and the second culture for being opened in 3 upper surface of the second dimethyl silicone polymer layer Slot 10, the first culture tank 9 are overlapped in 10 upper surface of the second culture tank, and the first culture tank 9 and the second culture tank 10 are cylindrical knot Structure is highly 1mm-2mm, and diameter 10mm-12mm, the right end of the first culture tank 9 is provided with and communicated with for placing outlet 12 Notch, the left end of the second culture tank 10 is provided with and communicated with the notch for placing inlet tube 11, and each culture pond is provided with Inlet tube 11 and outlet 12 in culture pond are extended to by 1 upper surface of the first polymethyl methacrylate layers, inlet tube 11 prolongs The bottom of notch on the left of culture pond is extended to, outlet 12 extends to the top of notch on the right side of culture pond.
The present invention uses stability, the robustness that polymethyl methacrylate (PMMA) sheathing material is due to this material And the transparency, and the internal material that dimethyl silicone polymer (PDMS) material is used as organ chip is then due to material itself Biocompatibility, elasticity and leakproofness, there are two miniature culture pond, culture ponds to be connected with extraneous microfluidic system for core inner setting It is recyclable to pump out different classes of cell culture fluid to support the cell being embedded in GelMA hydrogel to grow and due to entirety The transparency of chip can observe the growing state of three-dimensional micro-organs (liver micro-organs and kidney micro-organs) in real time.
Organ microchips of the invention double while comprising hydrogel cell culturing bracket with certain liquid crushing resistance, Wherein special detail setting is but also the subsequent Biology Observation that will be carried out and biomarker analysis are more easy.Together Sample can also supply nutrition required for two kinds of micro-organs by the culture fluid circulation of main support of microfluidic system in time And biomarker and waste caused by cell metabolism are taken away by efferent duct in time.Therefore, the double organs of entire liver-kidney Microchip, that is, analog human inner cell metabolism and nutriment exchange process.
With continuous research of the invention, the present invention has wide potential application foreground, other than drug screening, organ Chip also has revolutionary potentiality in terms of the human test of chemicals, toxin and cosmetics etc..WYSS research institute grinds Study carefully personnel and carries out toxin and Contaminant measurement using lung chip.
Meanwhile organ chip is also the new method that scientist imitates human diseases.Current many human diseases are not dynamic Object model, such as Crohn disease.Its pathogenic factor is unknown so far, also lacks effective treatment means, maximum reason is just It is that can not find to suffer from the animal of this disease equally to carry out drug test.And human mould is established using human body chip technology Type, this problem are just readily solved.
In terms of personalized medicine, usable genome editing technique successfully prepares individual pathological tissues chip at present, examines It examines and the effect that gene product corrects its defect is provided.Or patient is induced multi-potent stem cell into (iPS) and does specific cells induction point Human body chip is implanted into after change, to construct personalized drug toxicity Evaluation Platform.
The foregoing is merely illustrative of the preferred embodiments of the present invention, is not intended to limit the invention, all in essence of the invention Made any modifications, equivalent replacements, and improvements etc., should all be included in the protection scope of the present invention within mind and principle.

Claims (5)

1. a kind of double organs are coupled three-layer laminated integrated chip, it is characterised in that: including from top to bottom set gradually first Polymethyl methacrylate layers (1), the first dimethyl silicone polymer layer (2), the second dimethyl silicone polymer layer (3) and second are poly- Methyl methacrylate layer (4), the patch of the first dimethyl silicone polymer layer (2) and the second dimethyl silicone polymer layer (3) It is spaced apart and is set there are two culture pond on conjunction face, each culture pond is provided with by table on the first polymethyl methacrylate layers (2) Face extends to inlet tube (11) and outlet (12) in culture pond.
2. a kind of double organs according to claim 1 are coupled three-layer laminated integrated chip, it is characterised in that: the import Pipe (11) extends to the left bottom of culture pond, and the outlet (12) extends to the right hand top of culture pond.
3. a kind of double organs according to claim 1 are coupled three-layer laminated integrated chip, it is characterised in that: the second poly- first It is arranged on base methyl acrylate layer (4) there are two the circular hole (13) that diameter is 16mm-18mm, each circular hole (13) face one is trained Pond is supported, two culture ponds of micro- sem observation are easy to use by circular hole (13).
4. a kind of double organs according to claim 1 are coupled three-layer laminated integrated chip, it is characterised in that: described each Culture pond includes being opened in first culture tank (9) of first dimethyl silicone polymer layer (2) lower surface and being opened in second poly- two Second culture tank (10) of methylsiloxane layer (3) upper surface, first culture tank (9) are overlapped on the second culture tank (10) Surface.
5. a kind of double organs according to claim 3 are coupled three-layer laminated integrated chip, it is characterised in that: described first Culture tank (9) and the second culture tank (10) are cylindrical structure, are highly 1mm-2mm, diameter 10mm-12mm.
CN201811609624.8A 2018-12-27 2018-12-27 Double organs are coupled three-layer laminated integrated chip Pending CN109517739A (en)

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Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20150253309A1 (en) * 2012-09-28 2015-09-10 Tissuse Gmbh Multi-organ chip with improved life time and homoeostasis
CN106811413A (en) * 2015-11-30 2017-06-09 中国科学院大连化学物理研究所 Multiple organ chip based on microflow control technique and preparation method thereof
WO2018094003A1 (en) * 2016-11-16 2018-05-24 President And Fellows Of Harvard College Coupled organ-on-chip systems, devices, and methods of use for mimicking a de-coupled organ
CN209584263U (en) * 2018-12-27 2019-11-05 重庆大学 Double organs are coupled three-layer laminated integrated chip

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20150253309A1 (en) * 2012-09-28 2015-09-10 Tissuse Gmbh Multi-organ chip with improved life time and homoeostasis
CN106811413A (en) * 2015-11-30 2017-06-09 中国科学院大连化学物理研究所 Multiple organ chip based on microflow control technique and preparation method thereof
WO2018094003A1 (en) * 2016-11-16 2018-05-24 President And Fellows Of Harvard College Coupled organ-on-chip systems, devices, and methods of use for mimicking a de-coupled organ
CN209584263U (en) * 2018-12-27 2019-11-05 重庆大学 Double organs are coupled three-layer laminated integrated chip

Non-Patent Citations (3)

* Cited by examiner, † Cited by third party
Title
LEILA CHOUCHA-SNOUBER等: "Investigation of Ifosfamide Nephrotoxicity Induced in a Liver–Kidney Co-Culture Biochip", 《BIOTECHNOLOGY AND BIOENGINEERING》, vol. 110, no. 2, pages 599 *
SANGEETA N BHATIA等: "Microfluidic organs-on-chips", 《NATURE BIOTECHNOLOGY》, vol. 32, no. 8, pages 765 *
黄恒顺;邓九;李晓瑞;陈宗正;罗勇;: "微流控肠-肝-乳腺癌芯片的构建及其体外药物PK-PD分析", 中国实验方剂学杂志, no. 02 *

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