WO2016189527A1 - Systèmes de bio-impression à deux, trois et quatre dimensions - Google Patents

Systèmes de bio-impression à deux, trois et quatre dimensions Download PDF

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Publication number
WO2016189527A1
WO2016189527A1 PCT/IL2016/050537 IL2016050537W WO2016189527A1 WO 2016189527 A1 WO2016189527 A1 WO 2016189527A1 IL 2016050537 W IL2016050537 W IL 2016050537W WO 2016189527 A1 WO2016189527 A1 WO 2016189527A1
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WIPO (PCT)
Prior art keywords
additionally
energy
reservoir
donor material
waveguide
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PCT/IL2016/050537
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English (en)
Inventor
Aryeh Batt
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Photon Jet Ltd.
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Publication of WO2016189527A1 publication Critical patent/WO2016189527A1/fr

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    • CCHEMISTRY; METALLURGY
    • C23COATING METALLIC MATERIAL; COATING MATERIAL WITH METALLIC MATERIAL; CHEMICAL SURFACE TREATMENT; DIFFUSION TREATMENT OF METALLIC MATERIAL; COATING BY VACUUM EVAPORATION, BY SPUTTERING, BY ION IMPLANTATION OR BY CHEMICAL VAPOUR DEPOSITION, IN GENERAL; INHIBITING CORROSION OF METALLIC MATERIAL OR INCRUSTATION IN GENERAL
    • C23CCOATING METALLIC MATERIAL; COATING MATERIAL WITH METALLIC MATERIAL; SURFACE TREATMENT OF METALLIC MATERIAL BY DIFFUSION INTO THE SURFACE, BY CHEMICAL CONVERSION OR SUBSTITUTION; COATING BY VACUUM EVAPORATION, BY SPUTTERING, BY ION IMPLANTATION OR BY CHEMICAL VAPOUR DEPOSITION, IN GENERAL
    • C23C14/00Coating by vacuum evaporation, by sputtering or by ion implantation of the coating forming material
    • C23C14/22Coating by vacuum evaporation, by sputtering or by ion implantation of the coating forming material characterised by the process of coating
    • C23C14/24Vacuum evaporation
    • C23C14/28Vacuum evaporation by wave energy or particle radiation
    • CCHEMISTRY; METALLURGY
    • C23COATING METALLIC MATERIAL; COATING MATERIAL WITH METALLIC MATERIAL; CHEMICAL SURFACE TREATMENT; DIFFUSION TREATMENT OF METALLIC MATERIAL; COATING BY VACUUM EVAPORATION, BY SPUTTERING, BY ION IMPLANTATION OR BY CHEMICAL VAPOUR DEPOSITION, IN GENERAL; INHIBITING CORROSION OF METALLIC MATERIAL OR INCRUSTATION IN GENERAL
    • C23CCOATING METALLIC MATERIAL; COATING MATERIAL WITH METALLIC MATERIAL; SURFACE TREATMENT OF METALLIC MATERIAL BY DIFFUSION INTO THE SURFACE, BY CHEMICAL CONVERSION OR SUBSTITUTION; COATING BY VACUUM EVAPORATION, BY SPUTTERING, BY ION IMPLANTATION OR BY CHEMICAL VAPOUR DEPOSITION, IN GENERAL
    • C23C14/00Coating by vacuum evaporation, by sputtering or by ion implantation of the coating forming material
    • C23C14/04Coating on selected surface areas, e.g. using masks
    • C23C14/048Coating on selected surface areas, e.g. using masks using irradiation by energy or particles
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B29WORKING OF PLASTICS; WORKING OF SUBSTANCES IN A PLASTIC STATE IN GENERAL
    • B29CSHAPING OR JOINING OF PLASTICS; SHAPING OF MATERIAL IN A PLASTIC STATE, NOT OTHERWISE PROVIDED FOR; AFTER-TREATMENT OF THE SHAPED PRODUCTS, e.g. REPAIRING
    • B29C64/00Additive 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
    • B29C64/10Processes of additive manufacturing
    • B29C64/106Processes of additive manufacturing using only liquids or viscous materials, e.g. depositing a continuous bead of viscous material
    • B29C64/112Processes of additive manufacturing using only liquids or viscous materials, e.g. depositing a continuous bead of viscous material using individual droplets, e.g. from jetting heads
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B29WORKING OF PLASTICS; WORKING OF SUBSTANCES IN A PLASTIC STATE IN GENERAL
    • B29CSHAPING OR JOINING OF PLASTICS; SHAPING OF MATERIAL IN A PLASTIC STATE, NOT OTHERWISE PROVIDED FOR; AFTER-TREATMENT OF THE SHAPED PRODUCTS, e.g. REPAIRING
    • B29C64/00Additive 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
    • B29C64/20Apparatus for additive manufacturing; Details thereof or accessories therefor
    • B29C64/264Arrangements for irradiation
    • B29C64/268Arrangements for irradiation using laser beams; using electron beams [EB]
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B33ADDITIVE MANUFACTURING TECHNOLOGY
    • B33YADDITIVE MANUFACTURING, i.e. MANUFACTURING OF THREE-DIMENSIONAL [3-D] OBJECTS BY ADDITIVE DEPOSITION, ADDITIVE AGGLOMERATION OR ADDITIVE LAYERING, e.g. BY 3-D PRINTING, STEREOLITHOGRAPHY OR SELECTIVE LASER SINTERING
    • B33Y10/00Processes of additive manufacturing

Definitions

  • This invention generally relates to material printing, material deposition, and material distribution. More specifically the invention relates to new methods of laser induced forward transfer for enabling 2D, 3D or 4D printing of various materials, distribution of a plurality of materials, high resolution patterning, and improved methods of medical treatment and intervention, particularly in endoscopic procedures.
  • LIFT consists of a transparent substrate coated with a thin film of material to be transferred (the "donor"), which is facing a receiver substrate, (the “acceptor”).
  • a laser pulse locally induces a thermal excitation that finally results in material transfer towards the acceptor.
  • the LIFT method can be used to transfer a rather large number of different materials, e.g. copper, nickel, aluminum, and chrome.
  • laser transfer of liquid droplets was investigated both theoretically and experimentally with special emphasis on bio-materials.
  • the main problem of LIFT technology essentially used in academic research centers, is the complexity of the LIFT system, including (i) the Laser manipulation; (ii) the donor holding and supplying.
  • This invention overcome this inconvenience and complexity and brings LIFT means and method to industrial use for bio-printing.
  • Existing technologies and systems for bio-printing such as micropipettes, aerosol, pressurized nozzles and other, have limitations of droplet size, and even more critical limitations as effects of 'killing' of the living tissue and cells. Additional limitations are of the kind of materials that can be distributed in a repeatable, sustainable manner and with a controlled quality and accuracy.
  • the current invention covers basic technology for printing, deposition and distribution of biological and bio-compatible materials, and a system perspective comprising these technologies in bringing a comprehensive solution for several applications.
  • the basic applicable technologies to support the above are selected in a non-limiting manner from the group consisting of substrateless LIFT (SL-LIFT); Local Donor LIFT (LD-LIFT); new LIFT concepts; advanced sintering methods; and UV curing.
  • the present invention also brings new means and methods of producing and utilizing a simple, accurate, precise and effective Substrate-Less LIFT and Local-Donor LIFT targeted, inter alia, as a 2D, 3D and 4D bio-printing device, avoiding the need of a substrate enabling distribution mechanism.
  • the present invention discloses a system for performing substrateless and/or local donor Laser Induced Forward Transfer (LIFT), wherein said system comprises a reservoir (9) comprising at least one opening and an energy source configured to deliver energy to a donor material within said reservoir, thereby initiating a LIFT process or additional Induced Transfer process by other energy sources.
  • LIFT Laser Induced Forward Transfer
  • the present invention discloses a printing, material deposition, and material distribution system, characterized by: one or more printing heads, each of which comprises at least one distributor that distributes material by substrateless LIFT (SL-LIFT) and/or Local Donor LIFT (LD-LIFT) method; one or more material reservoirs, each of which contains or in connection with at least one material to be fed by said printing head in a continuous manner; and one or more energy sources in connection with said one or more reservoirs; and at least one energy source is adapted to generate said LIFT process.
  • the present invention further discloses a method of bio-printing and bio-material deposition by means of said system.
  • the present invention discloses a printing, material deposition, and material distribution system, as defined in any of the above, wherein laser operation parameters are selected from the group consisting of PW, PRF, power, pulse shape and other parameters can be controlled.
  • the present invention further discloses a method of printing and material distributing by means of said system.
  • the present invention discloses a printing, material deposition, and material distribution system, as defined in any of the above, wherein the laser source is distributed to several waveguides submerged in the reservoir, and acts each as an individual jetting apparatus.
  • the present invention discloses a printing, material deposition, and material distribution system, as defined in any of the above, wherein the laser is distributed by an energy distribution mechanism distributes the energy to at least one waveguide and at a time division or power division mechanism.
  • a heater selected from the group consisting of an energy source, CW laser, pulsed laser and any effective mechanism that heats the material locally in the reservoir.
  • the present invention discloses a printing, material deposition, and material distribution system, as defined in any of the above, wherein at least a portion of the walls of the reservoir and/or its opening is coated by a hydrophobic material, or is wetted by a wetting layer, or treated by a bio-compatible coating, or treated by elevated or reduced temperature thereby surface shape parameters are controlled and material properties and attributes are maintained.
  • each reservoir or printing head may receive material from any of the material main reservoir sources. It is another object of the invention to disclose a method as defined above, wherein the method further comprising a step of providing a feedback mechanism selected from the group consisting of a sensor, array of sensors, cameras, a source and detector, and any combination thereof.
  • It is another object of the present invention to present a SL-LIFT and LD-LIFT printing, material deposition, and material distribution system comprising the following modules: (a) a LIFT-based depositing mechanism that which distributes or deposits materials without utilizing a substrate; (b) one or more reservoirs for various materials, each of said materials feeds the deposition head continuously, semi continuously or in a batch- wise manner; and (c) an energy source and means to introduce or otherwise apply energy produced by said energy source to the material in said reservoir, thereby generating the LIFT process.
  • the apparatus may utilize a laser diode or LED or other energy source, or chemical process, that generates the crosslink process of biological cells.
  • the parameters that control the production of said arc are selected in a non-limiting manner from the group consisting of power, such as energy parameters, pulse duration, pulse shape, pulse frequency and any combination thereof.
  • the present invention discloses a printing, material deposition, and material distribution system, as defined in any of the above, wherein at least one resisting element receives power from a signal generator that controls parameters of the power, said parameters are selected from the group consisting of energy, pulse duration and frequency.
  • thermo-electric coolers Peltier module
  • heat pipes CW laser, pulsed laser and any combination thereof.
  • an optical element such as a lens, mirror, filter or a scanning element
  • a cooler selected from the group consisting of a thermo-electric cooler, Peltier module, heat pipes and any other cooling mechanism adapted to provide longer shelve life of the material.
  • an effective energy source such as a CW laser, pulsed laser and any other mechanism that heats the material locally within the reservoir.
  • It is another object of the present invention to present a medical device comprising a LIFT system adapted to embed a predefined material within or onto patient's body.
  • This LIFT system is utilizable without the necessity to prepare a substrate prior to distributing the material.
  • It is an object the present invention to present method producing a SL-LIFT system comprising steps of: providing a SL-LIFT or LD-LIFT deposition head; integrating therein one or more reservoirs for various materials; providing each of said materials in solid or liquid connection with said deposition head; integrating an energy source therein; and providing energy transfer means for applying energy to said material in said reservoir thereby generating a LIFT process.
  • the method additionally comprises providing at least one tube adapted to be embedded in or onto a medical device; and filling said at least one tube with said material.
  • the apparatus may utilize a laser diode or LED or other energy source, or chemical process, that generates the crosslink process of biological cells.
  • FIG. 1 schematically illustrates the conventional LIFT process known in the prior art
  • FIG. 2 schematically illustrates a substrateless LIFT (SL-LIFT) system according to one embodiment of the invention herein disclosed;
  • FIG. 3 schematically illustrates one embodiment of a five step SL-LIFT method
  • FIG. 4 schematically illustrates a non-limiting example of an energy profile provided by an energy source during the course of an SL-LIFT process according to one embodiment of the invention herein disclosed;
  • FIG. 5 schematically illustrates a non-limiting embodiment of the invention herein disclosed in which the system comprises a plurality of energy transfer means;
  • FIG. 6 schematically illustrates a method of a high speed printing process according to the invention herein disclosed in which a waveguide is translated vertically during the course of the process;
  • FIG. 7 schematically illustrates several embodiments of the invention that comprise addons to the waveguide and types of waveguides
  • FIG. 8 schematically illustrates a non-limiting embodiment of the system herein disclosed, in which the system comprises a rotating cylinder;
  • FIG. 9 schematically illustrates a non-limiting embodiment of the system herein disclosed, in which the system comprises a plurality of energy sources, a plurality of energy transfer means, a plurality of material feeders, and a mounting alignment mechanism;
  • FIG. 10 schematically illustrates a system with a plurality of printing heads according to one non-limiting embodiment of the invention herein disclosed;
  • FIG. 13 schematically illustrates feedback mechanisms added on to a printing head according to one non-limiting embodiment of the invention herein disclosed
  • FIG. 16 schematically illustrates the steps of a sintering process according to one embodiment of the invention herein disclosed;
  • FIG. 19 schematically illustrates the local-donor LIFT concept
  • PW pulse width
  • PRR pulse repetition rate
  • PRF pulse repetition frequency
  • LIFT laser- induced forward transfer
  • LD-LIFT linear discriminant-induced forward transfer
  • SL-LIFT substrateless laser-induced forward transfer
  • calibration is used herein to refer to the accuracy and orientation of the head in the system; and to the calibration of head parameters such as laser power, laser PW, laser PRF, heating and cooling temperatures, speed of movement of the waveguide, etc.
  • medical device refers herein to an instrument, apparatus, implant, in vitro reagent, or other similar or related article that is intended for use in the diagnosis of disease or other conditions, or in the cure, mitigation, treatment, or prevention of disease, or intended to affect the structure or any function of the body and which does not achieve any of its primary intended purposes through chemical action within or on the body or by being metabolized.
  • Non-limiting examples of "medical devices” include devices such as endoscopes and laparoscopes; pipettes and micropipettes; catheters; infusion equipment; recycling systems for biological fluids; implanted feeding tubes; irrigators; delivery systems for drugs, medicaments, biological molecules, nutrients, inorganic compounds, etc.; implantable pumps and tubing thereof; intradural drug injection and feeding systems; in situ delivery modules for neurological drugs and neurotransmitters; markers and biomarkers and derivatives thereof; contrast agents; etc.
  • an additional concept is provided that supports the curing or x-linking the biological cells thus completing the bio-printing process. This integrated technology provides a single comprehensive solution for tissue regeneration specifically and bio-printing in general.
  • a system in which one or more materials are deposited thus to complete the requirement of the specific tissue regenerated.
  • bio-printing system based on SL-LIFT and/or LD LIFT and/or LIFT that is complemented with a curing system based on laser or other illuminating or energy source, or chemical processing method.
  • the system comprises (i) at least one reservoir, at least one of said reservoirs at least partially filled by a material, (ii) at least one energy source, said light source is selected in a non-limiting manner form one or more members of a group consisting of: one or more lasers; one or more heating filaments; any other suitable mechanism and applicable means adapted to bring a required energy into said reservoir at a required location; and any combination thereof.
  • multiple independent energy sources are used.
  • these energy sources are selected from the group consisting of continuous wave (CW) lasers; and pulsed lasers.
  • the multiple independent energy sources may also comprise a local low-power laser for each printing head, each laser comprising a gain mechanism such as a ytterbium fiber.
  • the temperature of the reservoir(s) is controlled by a heating mechanism and/or by a thermoelectric heater/cooler, thus improving the donor material's properties for depositing, shelf life, and/or stability.
  • the system further comprises at least one waveguide with additional optics such as lenses, mirrors, coatings, or other optical elements.
  • the system further comprises a reservoir that can be filled in such way as to reduce or eliminate any need to disassemble or remove the printing head.
  • the system comprises a plurality of reservoirs.
  • the plurality of reservoirs may be a multi compartment reservoir; a plurality of independent reservoirs; or a sequence or train of reservoirs in fluid connection and fed by one or more central reservoirs.
  • the plurality of reservoirs are in fluid connection with one or more printing heads.
  • FIG. 1 illustrating schematically the LIFT process as it is known in the prior art: a transparent substrate (1) is coated with a thin film of the transferred material (3, the "donor”). A layer of donor material 3 faces the receiver substrate (7, the "acceptor”). There may be an intermediate layer between the substrate and donor layers.
  • a laser pulse (4) induces a local thermal excitation that results in rapid heat transfer to the donor material, generating a gas bubble (5) at the predefined focus point. The gas bubble rapidly travels to the surface and injects a droplet (6) from the boundary between the donor material and the ambient environment to the surface of the acceptor.
  • FIG. 2A illustrates schematically (not to scale) one embodiment of the improved LIFT system disclosed in the present invention.
  • the donor material itself is used as the donor substrate.
  • FIG. 2A provides a general illustration of the system.
  • a reservoir (9) contains the donor material (10).
  • An energy source or means for transferring energy from an energy source is disposed so as to be able to transfer energy to the donor material within the reservoir.
  • the energy source is a laser external to the reservoir, the light from which is transferred to the donor material via a waveguide (8). Any other appropriate energy source known in the art can be used, however. Non-limiting examples of energy sources used in embodiments of the invention not illustrated in FIG.
  • the reservoir comprises at least one opening 9b that enables material to exit. While the size of the opening is not critical to the operation of the system, in typical embodiments, it much larger than nozzles in typical inkjet printing heads. The increased size of the opening relative to those typically found in inkjet printing heads enables flow of large particles and of viscous materials without clogging the system. In preferred embodiments, the opening's largest dimension D4 (or diameter in embodiments in which it is circular) is at least 100 ⁇ , and may range up to several mm. In order to enable refilling of the reservoir without loss of material during the refilling, in preferred embodiments, the reservoir is provided with a stopper 9a.
  • one or more heating and/or cooling mechanisms are in thermal connection with the reservoir.
  • the viscosity of the material is controlled via heating of the material, while cooling can improve the shelf life of the material.
  • the heating mechanism is selected from the group consisting of resistive heating by at least one electrical filament, laser energy, and resistive heating from electrical current flowing through the reservoir walls; any other heating mechanism known in the art may be used as well.
  • the cooling mechanism is selected from the group consisting of thermoelectric coolers such as a Peltier module, heat pipes, and fluid flowing through the reservoir walls; any other cooling mechanism known in the art may be used as well.
  • the reservoir may be constructed from any of a variety of materials.
  • suitable materials for construction of the reservoir include plastics such as poly- and oligo- carbonates, metals and metal-containing compositions; and organic and inorganic compositions. Materials such as plastics that enable printing of acid materials are used in preferred embodiments.
  • the size of the opening of the reservoir (D4) can be adjustable or fixed. Adjustment of the opening of the reservoir enables control of the meniscus curvature in relation to the type of material, viscosity and required printing parameters. In some embodiments, control of the meniscus curvature is achieved by electro-wetting of the walls, heating of the material, heating or coating the walls of the opening, or a combination thereof. Control of the meniscus curvature is essential in order to receive uniform droplet properties from each energy source. In some embodiments of the invention, a vacuum or partial vacuum in the reservoir controls the boundary of the surface with the ambient environment.
  • FIG. 2B provides a close-up (not to scale) view of the LIFT process as it is performed in the novel system of the present invention.
  • the distal end of the energy source is placed at a distance Dl from the reservoir opening; in general, the energy source will be submerged in the donor material.
  • D2 represents the overall width of the energy source, while D3 the width of the core (active area, e.g. the waveguide in cases in which the energy source is a laser).
  • a gas bubble 11 is generated in the donor material.
  • a receiver substrate is placed facing opening 9b, an SL-LIFT process will occur in which the energy source in the reservoir acts as the donor substrate, without any necessity for a separate donor substrate.
  • the parameters of the energy applied to the donor material are controllable by a central mechanism, such as a laser with controllable PRR, PW, power, and rise time, an electrical pulse generator connected to the arc, and/or a resistance element.
  • a central mechanism such as a laser with controllable PRR, PW, power, and rise time, an electrical pulse generator connected to the arc, and/or a resistance element.
  • These embodiments can comprise one or more additional or alternative energy sources, such as a CW laser, electronic heater element, or any other heating module known in the art, that heat the material and thus modify its viscosity to a value adequate for the required printing parameters.
  • control of Dl the distance between the end of the energy source and the surface of the material, adds degrees of freedom setting droplet size and frequency of the process.
  • FIG. 3 illustrating in a non-limiting manner and not to scale a one embodiment of an SL-LIFT process that can be performed using the system disclosed herein.
  • the process illustrated in FIG. 3 is referred to herein as the "five step SL-LIFT process.”
  • step 1 a pulse of energy is applied from the energy source, causing a gas bubble to form (step 2).
  • step 3 the gas bubble forces donor material toward the reservoir opening 9b. Jetting, i.e. the bubble and donor material exit the reservoir and encounter the receiver substrate, occurs in step 4.
  • donor material from within the reservoir refreshes the interface.
  • the frequency with which these steps can be repeated in a system comprising a single energy transfer means e.g. a single waveguide
  • FIG. 4 illustrating a qualitative energy profile for the deposition of energy as a function of time during one embodiment of an SL-LIFT process performed by using one embodiment of the system disclosed herein.
  • a heat source such as a continuous wave (CW) laser or quasi-CW laser
  • CW continuous wave
  • This SL-LIFT process leads to a decreased refresh time of the material and an increased frequency.
  • throughput of the system increases and hence enables an additional degree of freedom in controlling and managing the droplet volume.
  • FIG. 5 illustrates schematically (not to scale) one reservoir in an embodiment of the system herein disclosed in which the system comprises at least one reservoir into which a plurality of energy sources or energy transfer means (e.g. a plurality of waveguides) have been introduced.
  • energy is transferred from a single energy source 15 such as a laser to energy distribution head 14.
  • the energy distribution head can divide the input energy into N parts, or can distribute the energy in time, e.g. by diverting the energy sequentially to each of the energy transfer means 13.
  • the energy transfer means can be a plurality of N waveguides.
  • the energy is then deposited simultaneously or sequentially to the donor material 10. Donor material removed from the reservoir is replaced by material stored in a material feeder (16) that is in fluid connection with the reservoir.
  • FIG. 6, illustrating a sequence of steps for an SL-LIFT process performed in the system herein disclosed according to one embodiment of the present invention.
  • the system and method herein disclosed enable filling the reservoir without any necessity for disassembly and assembly of the apparatus of which the reservoir is a part, e.g. a printing head, or for extracting the apparatus from the location in which it has been place, e.g. in the case of a tube implanted in situ in the body of a patient or in online fluid connection with an organ of patient's body.
  • the reservoir opening is closed while the reservoir is being filled in order that material will not flow out of the reservoir.
  • the opening can be opened and closed by control of the adjustable opening mentioned above, or by manipulation of a plug or stopper (9a) connected to the waveguide.
  • a plug or stopper (9a) connected to the waveguide.
  • vertical motion of the waveguide will bring the plug into position to seal the reservoir opening.
  • any other mechanical plug that can be electrically or vacuum controlled such as mechanical plugs, solenoids, and vacuum controllers, can be used.
  • throughput is also derived from the refresh rate, in addition to the laser PRR and other parameters.
  • the refresh rate is controlled by the viscosity of the material, as stated above regarding the heating; additionally or alternatively, it can be controlled by movement of the waveguide, an electric arc, or other energy transfer mechanism. Mechanical movement, such as a stirring in a lateral movement, applying ultrasonic vibration, etc., can be used to increase the refresh rate.
  • FIG. 7, illustrating (not to scale) non-limiting embodiments of the end tip of the waveguide in which it has been treated to improve the system performance and enable additional capabilities.
  • a local intermediate layer 18 can be provided (FIG.
  • An intermediate layer made of material with higher thermal conductivity than that of the waveguide will improve the efficiency of the heat transfer relative to a waveguide that lacks the intermediate layer, and also enables deposition of materials that are transparent at the output wavelength of the laser.
  • Cleaning of the energy transfer means is essential, since residual material may accumulate on its distal end, degrading system performance.
  • coating of the end tip with hydrophobic material, or shaping of the end is performed as a preventive measure.
  • mechanical cleaning of the tip is performed, for example, by extending the tip and brushing off excess material with an automatic or semiautomatic mechanism.
  • FIG. 7B presents a schematic illustration of a waveguide to which a lens (19) has been added.
  • FIG. 7C presents a schematic illustration of a waveguide tip to which Graded Index (GRIN) material (19a) has been added.
  • GRIN Graded Index
  • plates are added to assist focusing and to provide improved light transfer to the material.
  • Active components as MEMS and micro mirrors can be used to scan and distribute the energy at various locations on the meniscus and in the extracted state of the waveguide can be used to pattern, ablate and cure the deposited material.
  • FIG. 8 presenting a non-limiting schematic illustration (not to scale) of another embodiment of the SL-LIFT system disclosed in the present invention, an overall view of which is provided in FIG. 8A.
  • the system comprises a transparent rotatable cylinder (20) submerged in the reservoir; energy transfer means (e.g. a waveguide) (22) that transfers the energy to the donor material, a scanning mechanism (23), such as Galvo, MEMS, micro mirror or other scanning apparatus that directs the energy to a predetermined spot on the surface of the cylinder; and a mechanism for heating and cooling.
  • energy transfer means e.g. a waveguide
  • a scanning mechanism such as Galvo, MEMS, micro mirror or other scanning apparatus that directs the energy to a predetermined spot on the surface of the cylinder
  • a mechanism for heating and cooling As the cylinder rotates, it is coated with donor material, analogous to gravure printing, so that fresh material is continually presented to the energy transfer means.
  • the SL-LIFT process comprises (1) coating of the cylinder with donor material by rotation in the reservoir; (2) providing an energy pulse when a coated area reaches the floor of the reservoir, thereby initiating the LIFT process; and (3) removing and recoating the cylinder with donor material as it continues to rotate.
  • the cylindrical LIFT mechanism provides a dual technology head, serving both as an curing head and a deposition head.
  • One mode of operating said dual head is cleaning any material coating the cylinder; focusing energy on the printed substrate, which is possible because no material is coated on the cylinder; and scanning with the scanning mechanism (23) and removing or patterning or curing according to predefined data.
  • FIG. 9 illustrates (not to scale) an SL-LIFT printing head comprising the rotating cylinder illustrated in FIG. 8.
  • This printing head incorporates an advanced LIFT means, at least one first energy source (25) and at least one second energy source (30); an energy distribution mechanism (26) that is configured to receive the energy output of the energy sources and distribute it to the donor material (see FIG. 5), at least one first material feeding source (27) in fluid connection with the reservoir, at least one second material feeding source (31) in fluid connection with the reservoir, an adjustable mechanical interface (28) configured to manipulate and fix the tilt and orientation of the printing head, and a feedback mechanism to control the depositing process.
  • an advanced LIFT means at least one first energy source (25) and at least one second energy source (30); an energy distribution mechanism (26) that is configured to receive the energy output of the energy sources and distribute it to the donor material (see FIG. 5), at least one first material feeding source (27) in fluid connection with the reservoir, at least one second material feeding source (31) in fluid connection with the reservoir, an adjustable mechanical interface (28) configured to manipulate and fix the tilt
  • FIG. 10 providing a non-limiting schematic illustration of another embodiment of a printing head according to the present invention.
  • a plurality of N printing heads are mounted on a system and have interfaces to the energy distribution system (26), the material feeding source or sources (27), the electronics of the platform, the control mechanism of the platform and the platform software.
  • the system interfaces are described in detail below.
  • Material flow to the head reservoir is controlled by and supplied from the main material feeding system (27) or systems (27, 31) containing the various materials.
  • the system controls the flow.
  • filling of the reservoir is achieved by use of stopper 9a (FIG. 2); in embodiments comprising a cylindrical head, the cylinder is moved into position to close the reservoir's opening in order to enable filling of the reservoir.
  • the control system operates according one or more of the following: data and material data provided from a feedback mechanism, predefined material information which comprises inter alia droplet size and dimensions, material types etc.
  • the control system further adapted (i) to receive data from the feedback mechanism for the process control; and (ii) to tune droplet parameters, such as speed, power, etc.
  • the control system can further be set to control the movement of energy sources, scanning mirrors, optics, temperature cooling and heating, timing, cleaning according to feedback etc.
  • the control system of the head receives pattern data and material data from the platform and transforms it to coordinates and parameters required by the deposition head.
  • Non-limiting examples of such parameters include dimensions; locations and orientation of the cells; number of cells, shape and order of cells, neighboring of various types of cells; the type of cells being used; and parameters determining whether or not curing or x-linking is required.
  • the control system is also configured to receive data from the feedback mechanism for process control the process and for tuning of depositing parameters such as speed and power.
  • Non-limiting examples of system functions that may be controlled by the control system in preferred embodiments include the movement of the energy source, movement and positioning of the scanning mirror, movement and positioning of the optics, the temperature to be provided by the heating or cooling system, timing of cleaning, and the feedback mechanism.
  • Material flow to the reservoir is remotely controllable; material is supplied from a main material feeding system retaining one or more materials.
  • the electrical interface supplies power, inter alia, to the distributing head mechanism, and controls mirrors, fibers, heating and cooling mechanisms, reservoir operation etc.
  • the electrical interface is provided via one or more connectors and includes means for electrical control of the waveguide(s), fibers of the energy source etc.
  • FIG. 13 illustrates schematically (not to scale) a non- limiting embodiment of a feedback mechanism according to the present invention.
  • the feedback mechanism is incorporated into the printing head.
  • a sensor array such as a CCD or CMOS (32) or any other suitable array, photo-detector, quad detector or other power detector is mounted in or on the head.
  • the feedback mechanism may be integrated with the light source 33 or waveguide 35. Additionally or alternatively, it may be mounted external to the waveguide, for example, near the energy source 34 or one or more additional energy sources 34a.
  • the feedback mechanism is used to calibrate and synchronize the printing head(s) and to provide process control.
  • the multiple heads are can be calibrated during assembly.
  • the calibration is provided by calibration targets that are pre- manufactured or printed by the jetting head.
  • the calibration is supported by the control system, electronic mechanism and software.
  • the calibration output is saved and used by the application software.
  • each head can be calibrated independently with sufficient accuracy to support calibration of the multi-technology head.
  • the calibration mechanism that calibrates the printing head is based on the feedback obtained by the feedback mechanism.
  • calibration and registration targets can be pre-prepared on the printed platform or printed by the jetting mechanism and acquired by the feedback mechanism by any appropriate mechanism known in the art such as a sensor array, CCD, CMOS, etc.
  • FIG. 19 schematically illustrating (not to scale) the "local donor LIFT” (LD-LIFT) process of the present invention and how it contrasts with the standard LIFT process known in the prior art.
  • the standard LIFT process described above and illustrated in FIG. 19A comprises a substrate (201), a donor material (202), and focusing elements (203). Even if the size of the apparatus is reduced to a minimal dimension as shown in FIG. 19B, the standard LIFT process continues to operate, that is, the interaction between the energy source and the material 206 that is plated or coated on the donor substrate 205, and the consequent LIFT process, will be the same as in the standard prior art LIFT setup shown in FIG. 19A. The same basic physical phenomena will occur in the embodiment of the present invention illustrated in FIG.
  • the donor material 215 is embedded in, or part of, the reservoir.
  • the fundamental physical interaction between the energy source and the donor material will thus be the same as in FIG. 19B and hence as in the standard LIFT shown in FIG. 19A, demonstrating that a LIFT process will occur under conditions in which the material resides in or flows through the reservoir, even lacking a donor substrate.
  • the invention herein disclosed incorporates introduction of the local donor or donors into a reservoir (215), which continues to support a standard LIFT mechanism, thus deriving a "local donor LIFT" method and systems thereof.
  • Reservoir (215) may incorporate a flow of material, thereby refreshing the local donor (205) and enabling high frequency and continuous printing.
  • FIG. 20 schematically illustrating a system comprising a micro-tube LIFT distribution mechanism, an illumination source, a feedback mechanism, all embedded or otherwise incorporated in a tubular medical device.
  • Illumination source (110) is selected from a LED, SLED, laser diode or any other illumination source which emits light into a fiber or a bundle of fibers, thereby and illuminating an area that the material is deposited to.
  • This arrangement feedbacks sensor (111) to position, and provides accuracy and high yields in deposition of the material distributed by micro-tube (109).
  • Reservoir (109) is embedded into, in fluid connection with, or otherwise incorporated to the medical device.
  • An additional energy source (102a) functions as either feedback mechanism or a heating mechanism is transferred through the waveguide or alternatively, through an additional waveguide, and submerged in the material stored in the reservoir.
  • each waveguide further comprises means for moving each waveguide along its longitudinal axis.
  • means for moving each waveguide along its longitudinal axis include piezoelectric, magnetic, and microelectromechanical systems (MEMS).
  • MEMS microelectromechanical systems
  • these means are configured to be able to translate the waveguide(s) entirely out of the reservoir(s).
  • a system as defined in any of the above comprises a camera monitor to support registering, calibrating and monitoring of the depositing and curing process.

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  • Chemical & Material Sciences (AREA)
  • Health & Medical Sciences (AREA)
  • Toxicology (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Engineering & Computer Science (AREA)
  • Materials Engineering (AREA)
  • Mechanical Engineering (AREA)
  • Metallurgy (AREA)
  • Organic Chemistry (AREA)
  • Laser Beam Processing (AREA)

Abstract

Système permettant d'effectuer au moins l'une des actions suivantes : un Transfert Avant Induit par Laser (LIFY) (i) sans substrat et (ii) à donner local, ledit système comprenant un réservoir (9) comprenant au moins une ouverture ; et une source d'énergie conçue pour distribuer de l'énergie à un matériau donneur dans ledit réservoir et initier ainsi un procédé LIFT.
PCT/IL2016/050537 2015-05-26 2016-05-22 Systèmes de bio-impression à deux, trois et quatre dimensions WO2016189527A1 (fr)

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Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2014061024A1 (fr) * 2012-10-21 2014-04-24 Photon Jet Ltd Système d'impression à technologies multiples

Patent Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2014061024A1 (fr) * 2012-10-21 2014-04-24 Photon Jet Ltd Système d'impression à technologies multiples

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