WO2024189652A1 - Système automatisé et procédé de production d'organoïdes imprimés 3d personnalisés - Google Patents

Système automatisé et procédé de production d'organoïdes imprimés 3d personnalisés Download PDF

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Publication number
WO2024189652A1
WO2024189652A1 PCT/IN2024/050265 IN2024050265W WO2024189652A1 WO 2024189652 A1 WO2024189652 A1 WO 2024189652A1 IN 2024050265 W IN2024050265 W IN 2024050265W WO 2024189652 A1 WO2024189652 A1 WO 2024189652A1
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cell
organoid
automated
bio
ink
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English (en)
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Ikram Khan S.I
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Ismo Bio Photonics Pvt Ltd
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Ismo Bio Photonics Pvt Ltd
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    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N5/00—Undifferentiated human, animal or plant cells, e.g. cell lines; Tissues; Cultivation or maintenance thereof; Culture media therefor
    • C12N5/0062—General methods for three-dimensional culture
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B29—WORKING OF PLASTICS; WORKING OF SUBSTANCES IN A PLASTIC STATE IN GENERAL
    • B29C—SHAPING OR JOINING OF PLASTICS; SHAPING OF MATERIAL IN A PLASTIC STATE, NOT OTHERWISE PROVIDED FOR; AFTER-TREATMENT OF THE SHAPED PRODUCTS, e.g. REPAIRING
    • B29C64/00—Additive manufacturing, i.e. manufacturing of three-dimensional [3D] objects by additive deposition, additive agglomeration or additive layering, e.g. by 3D printing, stereolithography or selective laser sintering
    • B29C64/10—Processes of additive manufacturing
    • B29C64/106—Processes of additive manufacturing using only liquids or viscous materials, e.g. depositing a continuous bead of viscous material
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B29—WORKING OF PLASTICS; WORKING OF SUBSTANCES IN A PLASTIC STATE IN GENERAL
    • B29C—SHAPING OR JOINING OF PLASTICS; SHAPING OF MATERIAL IN A PLASTIC STATE, NOT OTHERWISE PROVIDED FOR; AFTER-TREATMENT OF THE SHAPED PRODUCTS, e.g. REPAIRING
    • B29C64/00—Additive manufacturing, i.e. manufacturing of three-dimensional [3D] objects by additive deposition, additive agglomeration or additive layering, e.g. by 3D printing, stereolithography or selective laser sintering
    • B29C64/20—Apparatus for additive manufacturing; Details thereof or accessories therefor
    • B29C64/205—Means for applying layers
    • B29C64/209—Heads; Nozzles
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B29—WORKING OF PLASTICS; WORKING OF SUBSTANCES IN A PLASTIC STATE IN GENERAL
    • B29C—SHAPING OR JOINING OF PLASTICS; SHAPING OF MATERIAL IN A PLASTIC STATE, NOT OTHERWISE PROVIDED FOR; AFTER-TREATMENT OF THE SHAPED PRODUCTS, e.g. REPAIRING
    • B29C64/00—Additive manufacturing, i.e. manufacturing of three-dimensional [3D] objects by additive deposition, additive agglomeration or additive layering, e.g. by 3D printing, stereolithography or selective laser sintering
    • B29C64/20—Apparatus for additive manufacturing; Details thereof or accessories therefor
    • B29C64/264—Arrangements for irradiation
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B29—WORKING OF PLASTICS; WORKING OF SUBSTANCES IN A PLASTIC STATE IN GENERAL
    • B29C—SHAPING OR JOINING OF PLASTICS; SHAPING OF MATERIAL IN A PLASTIC STATE, NOT OTHERWISE PROVIDED FOR; AFTER-TREATMENT OF THE SHAPED PRODUCTS, e.g. REPAIRING
    • B29C64/00—Additive manufacturing, i.e. manufacturing of three-dimensional [3D] objects by additive deposition, additive agglomeration or additive layering, e.g. by 3D printing, stereolithography or selective laser sintering
    • B29C64/30—Auxiliary operations or equipment
    • B29C64/35—Cleaning
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B29—WORKING OF PLASTICS; WORKING OF SUBSTANCES IN A PLASTIC STATE IN GENERAL
    • B29C—SHAPING OR JOINING OF PLASTICS; SHAPING OF MATERIAL IN A PLASTIC STATE, NOT OTHERWISE PROVIDED FOR; AFTER-TREATMENT OF THE SHAPED PRODUCTS, e.g. REPAIRING
    • B29C64/00—Additive manufacturing, i.e. manufacturing of three-dimensional [3D] objects by additive deposition, additive agglomeration or additive layering, e.g. by 3D printing, stereolithography or selective laser sintering
    • B29C64/30—Auxiliary operations or equipment
    • B29C64/386—Data acquisition or data processing for additive manufacturing
    • B29C64/393—Data acquisition or data processing for additive manufacturing for controlling or regulating additive manufacturing processes
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B33—ADDITIVE MANUFACTURING TECHNOLOGY
    • B33Y—ADDITIVE MANUFACTURING, i.e. MANUFACTURING OF THREE-DIMENSIONAL [3D] OBJECTS BY ADDITIVE DEPOSITION, ADDITIVE AGGLOMERATION OR ADDITIVE LAYERING, e.g. BY 3D PRINTING, STEREOLITHOGRAPHY OR SELECTIVE LASER SINTERING
    • B33Y10/00—Processes of additive manufacturing
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B33—ADDITIVE MANUFACTURING TECHNOLOGY
    • B33Y—ADDITIVE MANUFACTURING, i.e. MANUFACTURING OF THREE-DIMENSIONAL [3D] OBJECTS BY ADDITIVE DEPOSITION, ADDITIVE AGGLOMERATION OR ADDITIVE LAYERING, e.g. BY 3D PRINTING, STEREOLITHOGRAPHY OR SELECTIVE LASER SINTERING
    • B33Y30/00—Apparatus for additive manufacturing; Details thereof or accessories therefor
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B33—ADDITIVE MANUFACTURING TECHNOLOGY
    • B33Y—ADDITIVE MANUFACTURING, i.e. MANUFACTURING OF THREE-DIMENSIONAL [3D] OBJECTS BY ADDITIVE DEPOSITION, ADDITIVE AGGLOMERATION OR ADDITIVE LAYERING, e.g. BY 3D PRINTING, STEREOLITHOGRAPHY OR SELECTIVE LASER SINTERING
    • B33Y50/00—Data acquisition or data processing for additive manufacturing
    • B33Y50/02—Data acquisition or data processing for additive manufacturing for controlling or regulating additive manufacturing processes

Definitions

  • the present invention relates to the field of organoid formation involves multidisciplinary fields of cell biology, tissue engineering and biomedical engineering.
  • the present invention specifically discusses 3-dimensional organoid structure derived from patient specific tissues.
  • Organoids are tiny, self-organized three-dimensional tissue cultures that are derived from cells or stem cells. Such cultures can be crafted to replicate much of the complexity of an organ, or to express selected aspects of it like producing only certain types of cells. Organoids are in vitro miniaturized and simplified model systems of organs that have gained enormous interest for modelling tissue development and disease, drug screening and cell therapy.
  • organoids made from patient derived biopsy gives very accurate results at a very early stage of clinical trials. This helps in accelerating the clinical trials and reduce the time to market.
  • Three-dimensional Printing is one of the crucial factors in the area of medicine, particularly 3D bioprinting for organoids has capability to analyse the improvement and mechanisms of diseases along having a multitude of packages in regenerative therapies.
  • the invention provides a methods and systems for generating a three-dimensional (3D) structure corresponding to a biological material where a bio-printed three-dimensional matrices is generated based at least in part on the computer representations.
  • the high-throughput culture method generates organoids by means of microfluidics and then prints the organoids into a culture carrier by means of a 3D printing platform that can achieve convenient, fast and accurate printing, such that the size and structure of the organoids are suitable, uniform, and controllable, and the number of the organoids in a culture chamber of each culture carrier is constant.
  • organoids a drug sensitivity test and a toxicity test can be performed at the same time, and an accurate clinical prediction can be made.
  • the primary objective of the present invention is to provide a completely automated controller assisted bioreactor system that is capable of digesting and direct 3D printing of organoids from the patient derived biopsies or any cell line to produce a personalized /patient specific/ cell line specific organoid which mimics patient’s disease model
  • the present invention discusses a controller assisted system or device along with a method to produce bioink from primary tissues derived from tissue samples and generate a personalized organoid using direct organoid 3D printer integrated within the said system.
  • the system is a completely automated bioreactor capable of producing bioink from primary tissues derived from tissue samples obtained from the patient and generate a personalized patient specific organoid which mimics the patient’s disease condition. These organoids could be used to study personalized treatment and clinical trials.
  • the system to generate patient specific 3D organoids from patient’s biopsy comprises;
  • Receiving chamber configured to receive the patient derived cell sample
  • a Agitation and tissue digester chamber configured to mince the received cell sample and further enzymatically digest the received input tissue , the digested cells are subjected to washing and binding with target cell specific magnetic beads in the buffer and proceeded to magnetic sorter unit.
  • the Magnetic sorter unit sorts cells and isolates them to proceed further where they are expanded in culture conditions which are precisely regulated by the device
  • the sensors equipped in the system sense temperature, gas, pH , humidity to provide ambient conditions for cell survival and proliferation which can be selected using software,
  • the bioink preparation unit prepares bioink with ECM and other supporting factories
  • a bio-ink extrusion system including a extruder nozzle and control system where the cells are further directed to 3D printing units (supported by x, y and z axis movable motion control system) where the 3D printed patient derived organoids are generated.
  • the said method is supported with fluidic system to supply necessary materials for the cell growth along with a suite of sensors to maintain the ambient temperature or predetermined temperature , where the entire operations and system is microcontroller assisted and the system functions automatically.
  • the method to obtain a patient specific 3D organoid from patient’s biopsy includes:
  • Minced tissue is subjected to digestive enzyme of choice for a desired time period
  • the enzyme subjected tissue bits are separated using strainer, which separates tissues bits form the suspension cells or suspension
  • Figure 1 Illustrates the overall automated system for the preparation of 3D organoids
  • FIG. 2 Illustrates the expanded view of the Tissue digester and bio-ink making system and magnetic stirrer coil
  • Figure 3 Illustrates the expanded view of the tissue digestion and bioink preparation unit illustrating enzyme inlet, staged digestion and magnetic cell sorter.
  • Figure 4 Illustrates the 90 degree cut view and 60 degree cut view of the system
  • Figure 5 Illustrates the entire architecture of the system in nutshell
  • the present invention relates to a device to produce bioink from primary tissues derived from tissue samples and a direct organoid 3D bioprinter integrated with the controller assisted system. These 3D printed organoids are useful for disease diagnosis, chemotherapybased drug dosage for cancer patients, and also in translation medicine. Usually, to prepare an organoid from a pluripotent stem cell or primary, it would ideally take multiple weeks, but in the present direct 3D bioprinter, the preparation time of organoids prepared from bio-ink is reduced, and direct production of 3D print customized organoids of different size, shape, density, scaffolds, and cell combinations for efficient disease modelling and precise modelling of disease for in-vitro drug screening.
  • the present invention is emerging as a de novo piece of equipment that can develop an organoid with the patient’s cancer biopsy, thus generating primary cell organoids within the bioreactor
  • the present invention is a completely automated microcontroller assisted bioreactor that is capable of 3D printing organoids from the patient derived biopsies or cell lines.
  • the primary cells from the biopsies or cell lines will be converted to different organoids that mimic the patient’s disease model. These organoids will be a closely related model of study to plan the treatment regimen for personalized treatment and clinical trials.
  • This bioreactor will provide the essential conditions for the primary tissue processing or cell lines, organoid development and expansion similar to that of the biological niche.
  • the automated device automatically makes 3D printed organoids from the patient's biopsy or any cell line as per below steps
  • STEP- 1 We obtain a biopsy sample or cell line of the patient from the clinician. The sample will be transported in a buffer with antibiotics to prevent contamination. STEP-2: The tissue sample will be washed a couple of times with the buffer ( PBS + Abs buffer) to remove contaminating blood and other cells.
  • STEP-3 After washing, the tissues will be minced thoroughly. The tissue bits will be transferred to a tube containing the digestion enzyme of choice for the desired time period.
  • the generally used enzymes are collagenase, hyaluronidase.
  • STEP-4 The cell strainer will separate tissue bits from the suspension cells. The suspension will then be centrifuged to obtain the cell pellet.
  • STEP-5 The cells will be resuspended in media and will be sorted using Magnetic cell sorter.
  • STEP-6 After sorting, the cells will be expanded in culture with culture media and growth factors and supplements that support organoid growth for direct organoid 3D printing after mixing with ECM material with photoinitiator.
  • STEP-7 The generated organoids can be directly 3D printed into mass drug screening bioreactors used for different drug testing, toxicology studies and understanding new disease.
  • the chamber present in the system receives the tissue samples and is mixed finely for enzymatic digestion using enzymes like collagenase, hyaluronidase etc.
  • the cells are isolated, analyzed and expanded in culture conditions which are precisely regulated by the device.
  • the system is integrated with sensors like temperature, gas, pH and humidity to provide the required incubation environment for cell survival and proliferation based on the specific cell type protocol selected in the device's user interface software.
  • Organoid 3D printing system enables cell seeding onto the ECM for organoid development which will be further used for toxicology study.
  • the 3D printer chamber received pre-sorted cells from the previous stage and the 3D printer combines this cell in different ECM at different concentrations and combinations selectable through user interface software.
  • Organoid 3D printing system enables cell seeding onto the ECM for organoid development which will be further used for toxicology study.
  • the 3D printer chamber received magneticly sorted cells from the previous stage and the 3D printer combines this cell in different ECM at different concentrations and combinations selectable through user interface software.
  • the said system is compactly discussed in fig 1.
  • the present invention is a user-friendly, completely automatic device that can convert primary cells isolated from the patient's biopsy into organoids which provides highly specific treatment modalities to the patient by analysing the nature of cells or cancer that they exhibit.
  • This invention can be used in hospitals, pharma labs and Centres for cancer research where the treatment protocols for the patients can be tested, analysed and planned using the organoids developed.
  • this automated system avoids any human errors and improves the accuracy.
  • the present system comprising 3D bioprinter the preparation of organoids will take less than a week to prepare bio-ink and instantaneously 3D print customized organoids of different size, shape, density, scaffolds and cell combinations for efficient disease modelling for precise modelling of disease for in-vitro drug screening i.
  • the present invention is an automated microcontroller assisted system and method to produce a personalized 3D printed organoids from patient specific biopsy cells or any cell line.
  • the present system is a completely automated bioreactor capable of producing bioink from primary tissues and is integrated to a 3D printer to produce patient specific personalized organoids for studies.
  • the system comprises An inlet to receive the sample which can be any cell line or biopsy sample , the sample is generally received along with antibiotics and/or induced pluripotent stem cells.
  • ii A washing mechanism design to utlize a buffer to wash the tissue sample ; where the system is designed to wash the cells for n number of predetermined washes.
  • iii A mincing unit to mince the tissue sample iv.
  • the system consists of a Tissue digester and bio-ink making system 1, v.
  • the Tissue digester and bio-ink making system 1 has an extruder nozzle 6 through which the bioink is precisely ejected and an integrated UV light guided in Optical fiber cures (67) the bio-ink after printing in each individual well (63).
  • the digestion and mixing for enzymes is actuated by a Magnetic stirrer (7) which generates a rotating magnetic field around digestion and Cell Strainers chamber and its controlled by a h-bridge driver (61). Further, a specialized rotating and static magnetic field generator (9) is used in the Magnetic sorting chamber (26) and magnetic field is controlled with individual drivers (62) which is selectively activate each magnet with timers in a rotating sequence.
  • the Tissue digester and bio-ink making system 1 consists of two main stages, first is digestion and Cell Strainers chamber (24) which is responsible to collect the tissue or cell lines or IPSC fixed with different chemicals to do digestion and Cell Strainers.
  • Second part is Magnetic sorting chamber (26), in which cells received from chamber (24) are sorted to choose different cells required for printing.
  • First chamber is classified into 4 stages where each stage is separated by multiple fine filters (27,28,29) of pore size larger to smaller 120 um, 80 um and 50 um respectively, So that the cell of interest can be trapped in a 50 um chamber.
  • Each of this chamber has a Stirrer (10) which can be rooted with external magnetic generated by Magnetic stirrer (7).
  • magnetic stirrer (9) is capable of generating static and rotating magnetic fields. In rotating magnetic fields the mixing happens and when sorting magnetic field is applied cells get accumulated near these electro magnets, which can be demagnetized after magnetic cell sorting.
  • the components discussed above are illustrated clearly in fig 3.
  • Each of these chambers have stirrer and high impedance electrical pins responsible for measuring the level of liquid in each chamber (17). These pins are connected to amplifiers and ADC 56 for converting to digital and transferring to the microcontroller (71).
  • the bio ink extrusion system where the bio-ink Extrusion occurs through a needle (6) is precisely controlled, controlling the Output Extrusion control solenoid valve (60) connected to port (8) in synchronized with the pressure control system. Further, pH, temperature and DO in the chamber are monitored with optical sensors (66) as feedback to control the temperature inside the enclosure. Also, the magnetic field generator (9,7) itself acts like a heater to regulate the temperature of the chamber.
  • a pre-mixed gas of 5% CO2, 21 % oxygen and Balanced Nitrogen cylinder (39) is pumped by enabling solenoid (38) and passes through the air filter of (37). Further, the gas passes through flow sensor (35) to regulate flow rate and followed by the pressure sensor (34) to monitor pressure inside the chamber. Finally it passes through a humidifier chamber (36) with relative humidity regulated to around 95%. Further the air exists through the solenoid (30) and filter (31).
  • the port (11) in magnetic sorting chamber (26) is connected to a 3 -way solenoid valve (58) which connects to Magnetic particles for selective cell sorting fluid in bottle (59) in COM to NC.
  • valve 8 and air outlet port (15) are closed, so that pump (40) can increase the pressure inside the chamber and the fluid from port (11) can be sucked into the sorting chamber, further by switching valve (58) we can select bottle (59) with Hydrogel mixture with photo initiator bottle solenoid valve to prepare the bio-ink after the required cell types are sorted. All the solenoid valves are connected to the drivers (57) which is controlled by the microcontroller (71). viii. Further, This Extrusion chambers (9) and digestion/Cell Strainers chamber are connected with a thread (25) .
  • the chip has (4) ports, Air exit control port (12), Media inlet (13) , Gas mixture in port (14) and waste Outlet port (15).
  • a gas mixture for cell culture is pumped from port (13) to port (15) , this initially flows through the chip and then couples vertically to the chamber.
  • Port Media inlet 12 is a system which can select different liquids and pump through this port.
  • bottles culture Media, supplements and organoid growth factors bottle and 50, Digestion enzymes bottle 51, Tripsin bottle 52, extra bottle 53,Buffers/70% ethanol 54, and Extra bottle 55 are connect to a dedicated solenoid valves 44, 45,46,47,48,48 respectively and the output of this solenoids are connected to a coupler 43. Then the output of this coupler 43 is connected to pump 40.
  • any of the solenoids valves 44, 45,46,47,48,48 will be selected and by pumping selected liquid can be pumped to the system with solenoid 41 in Normally closed (NC-COM) state and flow in the direction of to the chamber 24.
  • NC-COM Normally closed
  • Solenoid 41 is put in Normally open state (ie NO to Com ) Now pump pumps the fluid towards each bottle by switching on solenoid 44, 45,46,47,48,48 one by one in order so that each and individual tubings can be cleaned with 70% ethanol in bottle 42.
  • a fiber coupled UV (65) source is located near the needle (6)which is enabled after every layer is printed for photo polymerization. This light source is drived with a constant current source driver 64.
  • a west eject port 14 on chip 21 which is controlled by solenoid 32 and waste is dumped in bottle 33.
  • a port 16 connecting the median pore size chamber in which final filter cells will be located, at the end of the cell filtering the cells will be transferred to magnetic sorting chamber via this port 16.
  • xi A plurality of control systems , viz an X and Y axis linear motion control system 2 with Z axis linear motion control system 3 for printing in 3 -dimension.
  • the entire system is covered by Enclosure with temperature, Humidity control and gas control enclosure 5 with heater and humidifier with integrated temperature and humidity sensor 68 connected to the microcontroller.
  • the entire system discussed is illustrated in fig 4 in both 90 degree cut view and 60 degree cut view .
  • the system has a Top lid 18, which is sealed with an air seal 19. This lid is opened and the partially minced tissue is placed inside this chamber top most chamber of digestion and Cell Strainers chamber 24 and Lid 18 is closed.
  • the chamber 24 is filled buffere and antibiotics to prepare the tissue for digession.
  • Digestion enzymes bottle from bottle 51 as discussed above state of valves positions and fluid flow direction till the top most camber with level sensor pinl7.
  • the chamber 24 comprises plurality of magnetic stirrers in descending order or pore size filters .
  • the Stirrer 10 has a fin-like structure, by adjusting the direction of its rotation with magnetic field the fluid inside the chamber can be directed to circulate between each of the chambers. By periodically changing the direction of rotation the digestion and sorting of cells is improved. 6. Once the digestion process is completed, the magnetic field is stopped and cells and debris settle in each of the filters
  • solenoid 32 which drains all the digestion enzymes to flow out from port 13 .
  • valve 8 and port 11 were closed, so no liquid flowed down to magnetic stirrer chamber 26 due to air lock.
  • the air seal is realized by opening the solenoid valve 71 which removes the air seal anc connects to output air filter 72. Now the sorter cells and the media flow down to the cell sorting chamber 26.
  • the stirrer 10 in the magnetic sorting chamber is rotated with 9 rotating magnetic field generation mode for few minutes. Now all the target cells will be bonded with beads. Rotating magnetic field is stopped and only one side magnet 9 is kept enabled, which makes the cell move to one side of the chamber and other debris can be washed out with a buffer through the exitruction port 18 by enabling valve 8. Now the magnetic sorting chamber is left with pure cells of interest. 12. Now the medium with growth factors and supplements that support organoid growth is pumped by enabling valve 44 to the meganitic sorting chamber for embryoid body formation, and induction.
  • the cells are embedded in a three-dimensional scaffold or a synthetic hydrogel. This matrix supports the cells and allows them to grow in a structure that mimics their natural environment .
  • Hydrogel mixture with photoinitiator 59 is pumped into the magnetic sorting chamber 26. Then mixed to create a homogeneous mixture of bio-ink which is ready for direct printing.
  • bio-ink generation system can be used as arrays for large scale tissue processing during personalized drug screening labs.
  • This system is not limited to one extrusion head to enable printing different organoids which plays a critical role in study of metastasis and multi organ models on the microfluidic chips. (The entire working is clearly indicated in fig 5)
  • this chambers are standalone to generate on demand bio-ink for personalized disease models for disease like cancer.

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Abstract

La présente invention concerne un système automatisé assisté par microcontrôleur et un procédé pour produire des organoïdes imprimés 3D personnalisés à partir de cellules de biopsie spécifiques à un patient ou d'une quelconque lignée cellulaire. Le présent système est un bioréacteur complètement automatisé capable de produire de la bio-encre à partir de tissus primaires et est intégré à une imprimante 3D pour produire des organoïdes personnalisés spécifiques à un patient pour des études. La génération d'organoïdes est commencée en prélevant des cellules de patients par biopsie, qui sont ensuite émincées et digérées par voie enzymatique. Ces cellules sont triées à l'aide d'un trieur de cellules et développées. Le système est équipé pour générer une bio-encre qui est extraite de manière régulée pour imprimer un organoïde 3D personnalisé généré à partir de cellules spécifiques à un patient à l'aide d'une bio-imprimante 3D incorporée dans le système. Le système peut générer des sphéroïdes et des organoïdes qui supportent diverses applications.
PCT/IN2024/050265 2023-03-14 2024-03-14 Système automatisé et procédé de production d'organoïdes imprimés 3d personnalisés Ceased WO2024189652A1 (fr)

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Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN119589951A (zh) * 2024-11-14 2025-03-11 清源至芯(深圳)生物科技有限公司 打印喷头装置、挤出式类器官3d打印机、通讯模块及类器官打印方法

Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20180257297A1 (en) * 2017-03-10 2018-09-13 Prellis Biologics, Inc. Methods and systems for printing biological material

Patent Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20180257297A1 (en) * 2017-03-10 2018-09-13 Prellis Biologics, Inc. Methods and systems for printing biological material

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN119589951A (zh) * 2024-11-14 2025-03-11 清源至芯(深圳)生物科技有限公司 打印喷头装置、挤出式类器官3d打印机、通讯模块及类器官打印方法

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