CN108359604A - A kind of conveying of stem cell seed and microenvironment regulating system - Google Patents

A kind of conveying of stem cell seed and microenvironment regulating system Download PDF

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Publication number
CN108359604A
CN108359604A CN201810070731.1A CN201810070731A CN108359604A CN 108359604 A CN108359604 A CN 108359604A CN 201810070731 A CN201810070731 A CN 201810070731A CN 108359604 A CN108359604 A CN 108359604A
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China
Prior art keywords
stem cell
chamber
limited
cavity
conduit
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CN201810070731.1A
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Chinese (zh)
Inventor
张海军
尹玉霞
卢天恒
陈凤英
侯文博
周超
鲁守涛
段翠海
刘光
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Shandong Branden Medical Devices Co Ltd
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Shandong Branden Medical Devices Co Ltd
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Priority to CN201810070731.1A priority Critical patent/CN108359604A/en
Publication of CN108359604A publication Critical patent/CN108359604A/en
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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
    • C12M41/00Means for regulation, monitoring, measurement or control, e.g. flow regulation
    • C12M41/26Means for regulation, monitoring, measurement or control, e.g. flow regulation of pH
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61MDEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M5/00Devices for bringing media into the body in a subcutaneous, intra-vascular or intramuscular way; Accessories therefor, e.g. filling or cleaning devices, arm-rests
    • A61M5/178Syringes
    • A61M5/19Syringes having more than one chamber, e.g. including a manifold coupling two parallelly aligned syringes through separate channels to a common discharge assembly
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61MDEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M5/00Devices for bringing media into the body in a subcutaneous, intra-vascular or intramuscular way; Accessories therefor, e.g. filling or cleaning devices, arm-rests
    • A61M5/178Syringes
    • A61M5/31Details
    • 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
    • C12M41/00Means for regulation, monitoring, measurement or control, e.g. flow regulation
    • C12M41/12Means for regulation, monitoring, measurement or control, e.g. flow regulation of temperature
    • 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
    • C12M41/00Means for regulation, monitoring, measurement or control, e.g. flow regulation
    • C12M41/30Means for regulation, monitoring, measurement or control, e.g. flow regulation of concentration
    • C12M41/36Means for regulation, monitoring, measurement or control, e.g. flow regulation of concentration of biomass, e.g. colony counters or by turbidity measurements
    • 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
    • C12M41/00Means for regulation, monitoring, measurement or control, e.g. flow regulation
    • C12M41/40Means for regulation, monitoring, measurement or control, e.g. flow regulation of pressure

Abstract

The present invention discloses a kind of conveying of stem cell seed and microenvironment regulating system and its method for production, is applied to stem cell target and transplants, belongs to biotechnology and regenerative medicine field.The agent structure of the invention includes that 2 or multiple containing liquid chambers correspond to the conduit of two-chamber or multi-cavity with developing mark.Different containing liquid chambers and tube chamber can be used for conveying stem cell seed, pumpback tissue fluid and cell, conveying bioactie agent and real time monitoring graft state.The system can adjust therapeutic strategy in time, and periodically precisely conveying supplement stem cell seed and bioactie agent, adjusting cell seed surrounding microenvironment sequencing promote proliferation and the differentiation of stem cell.The invention can solve the problem of stem cell transplantation survival efficiency is low, and functionalization level is low, easy diffusive migration, repeatedly transplanting wound and infection.

Description

A kind of conveying of stem cell seed and microenvironment regulating system
Technical field
The invention belongs to biotechnologys and regenerative medicine field, and in particular to a kind of conveying of stem cell seed and microenvironment tune Section system.
Background technology
With the development of medical research and science and technology, more and more disease types are realized and capture, and give vast trouble Person and family have sent to Gospel.But still have a large amount of disease conventional therapy means not good enough, cannot be satisfied sufferer to curative effect persistence, Small side effects and the requirement for facilitating beauty.Stem cells technology, also known as regeneration medicine technology are a kind of modern times that developed recently gets up Biotechnology is the third-largest bioscience achievement after clone technology, genetic engineering.Stem cell have it is " unlimited " proliferation, it is more To differentiation potential, it can be divided into multiple functions cell or tissue organ, be referred to as " general-purpose cell " in medical field.By to dry Cell detached, in vitro culture, directional induction, the even processes such as genetic modification, breed out in vitro it is completely new, normal very To younger cell, tissue or organ, and may be implemented to clinical disease eventually by the transplanting of cell tissue or organ Treatment.Especially autologous stem cells have safe and non-toxic, and non-immunogenicity, source is sufficient, therapeutic domain is wide, it is considered to be best Immunization therapy and gene therapy vector.Cellular replacement therapy is widely used in the nervous system disease field(As brain paralysis, brain lack Blood, spinal cord injury, motor neuron disease, Parkinson's disease etc.), disease of immune system(Such as diabetes, leukaemia, AIDS)With And heart disease, muscular atrophy, skin injury, eye disease, breast reconstruction shaping etc..The means of currently used stem cell transplantation Have through blood circulation injection, through cerebrospinal fluid injection and local orthotopic transplantation etc..Include being injected intravenously and moving through blood circulation injection Arteries and veins is injected, easy to operate, wound is small, is easily accepted by patients, but transplants that targeting is poor, and through a long time, which migrates, to be caused largely to transplant Cell is consumed in blood circulation, and stem cell survival and field planting rate are low, or even cannot be introduced into focal area.It is noted through cerebrospinal fluid It penetrates for the nervous system disease, shortens circulation time, but the ingredient of cerebrospinal fluid is different from blood and there are blood-brain barrier, Affect the success rate of stem cell transplantation.Stem cell migration ability and Multidirectional Differentiation ability are strong, and orthotopic transplantation is in addition to that will reduce pair Except the damage of transplantation site, the survival rate of transplanting stem cell returned leakage migration, improve stem cell seed should be also reduced, is determined Break up to induction.In addition to this, cellular replacement therapy is there are the risk of long term complication such as tumour, how EARLY RECOGNITION and to press down The generation of tumour processed is also one of the necessary Consideration of stem-cell therapy.
It is new through looking into, in stem cell transplantation field, it there is no the patent that can effectively solve clinical problem both at home and abroad at present.It is Chinese special Sharp CN201520124142.9 discloses a kind of autologous tissue's engineering stem cell transplantation operation special syringe, including cavity circle Pipe, plunger tube core and injection needle, it is plastic simplicity, of low cost, the local injection of stem cell seed may be implemented.It is Chinese special Sharp CN201320476307.X discloses a kind of Subretinal space stem cell transplanter.It is promoted by syringe needle, casing, injection power Pipe, spiral cover, the syringe needle, casing, injection power propulsion tube, spiral cover, linear motor, power supply, control switch, quantitative storage pipe, The compositions such as positioning limiting fixator, it is easy to operate, securely and reliably, overcomes two people and operate the uncoordinated wind for wearing out retina brought Danger.
When consulting long-time vein medication or being transfused the patent of nutrition, Chinese patent CN201510158575.0 discloses one Kind check valve sealing-free tube implanted administration device, including drug delivery device main body, conduit and locking device.By using this hair Bright, drug can be directly entered specified location and play targeted therapy, and can effectively avoid drug reflux obstruction conduit.This hair Bright injection seat and conduit are single cavity structure, are had a single function.Stem cell seed conveys and microenvironment regulating system is according to required work( The diversity of energy, structure is increasingly complex, combines each friendship such as mechanical processing, Biomaterials Modification, optical sensor, biochemistry Subject is pitched, analysis and defeated periodically is carried out to stem cell seed and its periphery microenvironment by the way that multi-cavity structure and induction system are orientable Supplement stem cell seed and bioactie agent are sent to realize that stem cell seed is repeatedly to the fine adjustment of cell micro-environment The sequencing of plantation, the multiple biological activities factor is transfused Trinitarian accurate cellular replacement therapy.
Invention content
The present invention discloses a kind of conveying of stem cell seed and microenvironment regulating system and its method for production, is applied to stem cell Transplantation treatment is targeted, biotechnology and regenerative medicine field are belonged to.The agent structure of the invention includes 2 or multiple containing liquid chambers The implanted stem cell conveying of corresponding two-chamber or multi-cavity catheter and study on microenvironment regulation system.It can continue including the system, repeatedly, The growth conditions and cell function of periodic monitoring stem cell, adjusting therapeutic strategy in time, periodically precisely conveying supplements stem cell seed And bioactie agent, adjust proliferation and differentiation that cell seed surrounding microenvironment sequencing promotes stem cell.The invention can Solve the problem of stem cell transplantation survival efficiency is low, and functionalization level is low, easy diffusive migration, repeatedly transplanting wound and infection.
The present invention relates to the orientable periodically conveying supplement stem cell seed of one kind and bioactie agents, adjust cell seed Surrounding microenvironment is chronically implanted formula two-chamber or multi-cavity transport system.The system includes two-chamber or multi-cavity injection seat, band development mark Two-chamber or multi-cavity valve conduit, buckle of note etc..The injection seat internal cavity structures with macromolecule material film carry out every Disconnected, cavity top is Arcuate puncture window, and bottom is the metal gasket of anti-penetration;Injection seat lateral opening circular channel is for connecting The conduit, internal cavities are corresponding with conduit two-chamber or multi-cavity structure to be communicated;The conduit be two-chamber or multi-cavity structure, tail end with Injection seat be connected, head end radiography plug closing, the conduit head end at radiography plug 0.5-1cm through medical adhesive water process, can With rapid closing blood vessel/tissue, stem cell/stem cell planting body is avoided to return leakage.Respectively there is a three-dimensional in each tube chamber side of conduit head end Valve plays the role of counterflow-preventing.Valve catheter should have good flexibility and elasticity, adapt to subcutaneously or intramuscularly implantation and pull Needs.First containing liquid chamber of the transport system and tube chamber can convey stem cell seed, second containing liquid chamber as needed The differentiation degree and cell function for the stem cell that can be transplanted with pumpback tissue fluid and raji cell assay Raji with tube chamber, third containing liquid chamber with Tube chamber can convey bioactie agent and adjust stem cell transplantation microenvironment.Inductor system can be added in 4th containing liquid chamber and tube chamber System, realize pH, pressure, temperature, graft density and volume real time monitoring.There is circuit in storehouse, bio signal can be converted Afterwards data exchange is carried out with external reception system.
Using the above design scheme, the invention has the advantages that:
1, Preserving time, can periodically sampling monitoring transplanting stem cell growth and differentiation state and cell function, in time adjustment control Treat strategy;
2, Preserving time periodically can precisely convey supplement stem cell seed, and solution stem cell transplantation survival efficiency is low, repeatedly moves Plant the problem of wound and infection;
3, Preserving time periodically can precisely convey bioactie agent, adjust cell seed surrounding microenvironment sequencing and promote to do The proliferation of cell and differentiation.
4, Preserving time can realize the real-time prison of pH, pressure, temperature, graft density and volume etc. by inductor Control.
5, Preserving time, can regular sample detection tumor cell marker, avoid graft from generating tumor-like lesion.
6, medical adhesive water process conduit head end can avoid stem cell/stem cell planting body with rapid closing blood vessel/tissue Return leakage.
7, respectively there is a three-dimensional valve in each chamber side of conduit head end, plays the role of counterflow-preventing.
8, the use of whole device can make stem cell transplantation realize real time monitoring, adjust in real time, in due course supplement three one Body fully accomplishes individuation immunotherapy targeted autoantibody.
Description of the drawings
Fig. 1 is Endermic implantating two-chamber of the present invention or the structural schematic diagram of multi-cavity transport system appearance
Fig. 2 is the internal structure schematic diagram pattern 1 of the invention agent structure injection seat
Fig. 3 is the internal structure schematic diagram pattern 2 of the invention agent structure injection seat
Fig. 4 is the internal structure schematic diagram pattern 3 of the invention agent structure injection seat
Fig. 5 is the internal structure schematic diagram pattern 4 of the invention agent structure injection seat
Wherein:1 injection seat;2 threading holes;3 conduits are locked;4 buckles;5 conduits;6 three-dimensional valves;7 radiography plugs;8 Arcuate punctures Window;9 first chambers;10 second chambers;11 diaphragms;12 third chambers;13 the 4th chambers;14 conduit connections
Two, the surgical implantation of the invention device
Injection pedestal should be embedded at the subcutaneous 0.5 ~ 1.0cm of no damaged skin, should have bone structure support, such as rib surface, ilium Surface, should not be placed under abdomen (injection pedestal invagination easily occurs) or costal margin (leads to costal margin pain).After local anaesthesia, in selected entrance An osculum is cut at place, and embedding injection seat fixes pedestal and tissue by threading hole with degradable suture.It is led with tunnel guide Pipe is positioned at stem cell transplantation, and injection seat is connected with the catheter tip after trimming with buckle and is locked.
Three, the Clinical practice of the invention device
Apparatus of the present invention can be used for stem cell seed transplantation treatment and supplementary therapy in the future for the first time.Transplantation treatment for the first time:Such as mesh Mark position is cavity structure, can measure target site volume by inductor system, the quantity of stem cell is transplanted in estimation for the first time;
By not damaged needle pierces skin and Arcuate puncture window, into first chamber, connection disposable syringe is injected suitable Measure stem cell seed suspension.Daily monitoring:By inductor system, to pH, pressure, temperature, shifting around stem cell graft Plant growth density and volume are monitored in real time.Supplementary therapy:By not damaged needle pierces skin, Arcuate puncture window and Can self-healing film, into second chamber, connection disposable syringe injects appropriate physiological saline and pumpback tissue fluid, in tissue fluid Including part cell, can be detected various thin by the cell growth and differentiation situation at flow cytomery stem cell transplantation The content of intracellular cytokine and tumour cell marker etc..It needs to formulate individualized treatment strategy with clinic according to testing result, in due course New stem cell seed and bioactie agent are supplemented in right amount, are completed respectively by first chamber and third chamber.
Above to illustrate the specific implementation mode for describing the present invention, protection scope of the present invention is wanted by appended right Book is asked to limit.Those skilled in the art, can be to these embodiment party under the premise of without departing substantially from the principle and substance of the present invention Formula makes numerous variations or change, but these change and modification each fall within protection scope of the present invention.

Claims (13)

1. the present invention relates to a kind of orientable periodically precisely convey that can be used for a long time to supplement stem cell seed and bioactivity The factor adjusts the Endermic implantating transport system of stem cell transplantation microenvironment;It is characterized in that, the system is noted by two-chamber or multi-cavity Penetrate seat, the two-chamber with development or multi-cavity valve catheter and buckle three parts composition;The injection seat is that internal double layers or multilayer are empty Cavity configuration, cavity top are Arcuate puncture window, and cavity is separated by polymer separators, and bottom is metal gasket;Injection seat For connecting the conduit, each containing liquid chamber is corresponding with each chamber of conduit to be communicated lateral opening circular hole;The conduit is two-chamber or multi-cavity Structure, tail end are connected with injection seat, and the closing of head end radiography plug, respectively there is a valve in each cavity side at head end 5mm-10mm Film;The structure of the Endermic implantating two-chamber or multi-cavity transport system mainly may include:1 is injection seat, and 2 be threading hole, and 3 be conduit Lock, 4 be buckle, and 5 be conduit, and 6 be three-dimensional valve, and 7 be radiography plug.
2. according to claim 1, the injection seat shell is not limited to the materials such as stainless steel, titanium alloy, macromolecule or ceramics.
3. according to claim 1, the injection seat punctures window and is not limited to the high molecular materials such as silica gel, polyurethane, thermoelastic, thick Degree is 1-5mm, and can tolerate not damaged syringe needle, repeatedly puncture has no exfoliation.
4. according to claim 1, the injection seat cavity is not limited to two-chamber or multi-cavity, and diaphragm is not limited to silica gel, polyurethane, thermoelastic Property the high molecular materials such as body, material therefor should have certain elasticity, after puncture can self-healing, keep the isolation shape between cavity State.
5. according to claim 1, the injection seat metal gasket, which is not limited to pure titanium, titanium alloy, stainless steel, platinum etc., to be stopped The material of sharp pin puncture.
6. according to claim 1, the injection holder structure is not limited to Fig. 2, Fig. 3, Fig. 4 or Fig. 5 and other possible types, wherein 8 be Arcuate puncture window, and 9 be first chamber, and 10 be second chamber, and 11 be diaphragm, and 12 be third chamber, and 13 be the 4th chamber, 14 For conduit connection;There are two threading holes for the edge distribution of pedestal, are convenient for the fixation of injection seat and tissue.
7. according to claim 1, the conduit is two-chamber or multi-cavity valve catheter, is not limited to medical silica-gel, PEBAX or polyurethane Equal high molecular materials, should have preferable elasticity;First containing liquid chamber and tube chamber can convey stem cell seed, as needed The differentiation degree and cell function for the stem cell that two containing liquid chambers and tube chamber can be transplanted with pumpback tissue fluid and raji cell assay Raji, third A containing liquid chamber and tube chamber can convey bioactie agent and adjust stem cell transplantation microenvironment;4th containing liquid chamber and tube chamber can add Enter inductor system, realize pH, pressure, temperature, graft density and volume real time monitoring.
8. according to claim 1, the conduit is two-chamber or multi-cavity valve catheter;Conduit head end radiography plug is not limited to sulfuric acid pair One or several kinds in methylaminophenol, hydroquinone, CD-2, CD-3, CD-4 are used in combination as developer;The conductor housing End, through medical adhesive water process, can avoid stem cell/stem cell at radiography plug 0.5-1cm with rapid closing blood vessel/tissue Planting body returns leakage;Respectively there is a valve in each chamber side of conduit head end, plays the role of counterflow-preventing.
9. according to claim 1, the buckle is not limited to the materials such as polypropylene, is not limited to internal thread locking or the shapes such as physics blocks Formula, by injection seat and conduit clamping fixed, whole device is linked together, and is avoided the loosening of conduit, transposition or is fallen off, it is ensured that product Normal use.
10. according to claim 1, the Endermic implantating two-chamber or multi-cavity transport system material therefor be not limited to metal, macromolecule, The compound use of ceramics and different materials, but the mechanical performance using position should be met and have good biocompatibility.
11. according to claim 1, the stem cell of the Endermic implantating two-chamber or the conveying of multi-cavity transport system is not limited to fill between marrow Matter stem cell, neural stem cell, fat stem cell, pancreatic stem cell, Cardiac Stem Cells and its directed differentiation or genetic modification are thin Born of the same parents etc.;Bioactie agent is not limited to Porcine HGF, DNA or the polypeptide of various suitable stem cell growths, and can catch Albumen or the polypeptide etc. of stem cell seed or endogenous retinal stem cells are obtained, combination is not limited to commonly mixing, physical absorption and change Learn reaction etc.;The disease treated is not limited to cardiovascular and cerebrovascular disease, disease of immune system, beauty and shaping etc..
12. according to claim 7, inductor system is not limited to pressure inductor, bio signal inductor and fiber sensor etc.; The function of realization is not limited to the real time monitoring etc. of pH, pressure, temperature, graft density and volume.
13. according to claim 8, medical glue composition is not limited to chemical glue, biogum or compound adhesive etc..
CN201810070731.1A 2018-01-25 2018-01-25 A kind of conveying of stem cell seed and microenvironment regulating system Pending CN108359604A (en)

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Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN112980690A (en) * 2019-12-17 2021-06-18 华东数字医学工程研究院 PDX model incubation device and anti-tumor drug screening method
CN114292729A (en) * 2021-12-23 2022-04-08 山东百多安医疗器械股份有限公司 Cell culture environment regulation and control device and operation method

Citations (5)

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Publication number Priority date Publication date Assignee Title
CH546076A (en) * 1971-02-11 1974-02-28 Ampoules Inc MULTI-CHAMBER INJECTION CARTRIDGE.
US20040030282A1 (en) * 2002-08-09 2004-02-12 Toby Freyman Injection devices that provide reduced outflow of therapeutic agents and methods of delivering therapeutic agents
US20120100600A1 (en) * 2002-06-20 2012-04-26 Primeradx, Inc. Apparatus for polynucleotide detection and quantitation
CN104368059A (en) * 2014-11-18 2015-02-25 肖程午 Minimally invasive intervention implantable drug-supplying device with one-way valve
CN105126237A (en) * 2015-06-26 2015-12-09 中国人民解放军总医院 Double-mode heart in-situ perfusion system

Patent Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CH546076A (en) * 1971-02-11 1974-02-28 Ampoules Inc MULTI-CHAMBER INJECTION CARTRIDGE.
US20120100600A1 (en) * 2002-06-20 2012-04-26 Primeradx, Inc. Apparatus for polynucleotide detection and quantitation
US20040030282A1 (en) * 2002-08-09 2004-02-12 Toby Freyman Injection devices that provide reduced outflow of therapeutic agents and methods of delivering therapeutic agents
CN104368059A (en) * 2014-11-18 2015-02-25 肖程午 Minimally invasive intervention implantable drug-supplying device with one-way valve
CN105126237A (en) * 2015-06-26 2015-12-09 中国人民解放军总医院 Double-mode heart in-situ perfusion system

Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN112980690A (en) * 2019-12-17 2021-06-18 华东数字医学工程研究院 PDX model incubation device and anti-tumor drug screening method
CN112980690B (en) * 2019-12-17 2022-10-21 华东数字医学工程研究院 PDX model incubation device and anti-tumor drug screening method
CN114292729A (en) * 2021-12-23 2022-04-08 山东百多安医疗器械股份有限公司 Cell culture environment regulation and control device and operation method

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Application publication date: 20180803