The present invention relates to compact drop-on-demand systems, in particular, those systems that involve the absorption of light to eject micro-droplets of viscous or inviscid fluids.
Drop-on-demand technology is now a mature technology, having a profound impact on manufacturing processes, and is used for instance in inkjet printing, additive manufacturing or contactless drug delivery devices. Drop-on-demand systems can be classified according to the way they are actuated, their compactness, resolution, and the type of liquids they can dispense.
Most consumer desktop inkjet printers are based on thermal actuation. In each chamber, a resistor is in contact with the ink and upon actuation; it vaporizes a small volume of the ink, pushing towards the nozzle the rest of the ink, therefore generating a droplet. This approach allows for densely packing ink chambers and nozzles. The droplet size and therefore the resolution of the system are defined by the nozzle diameter. Furthermore to avoid clogging of the nozzle, the ink needs to have a low viscosity, typically around 10 mPa·s, and the nozzle diameter needs to be large enough, typically more than 50 μm. Murphy S V, Atala A., “3D bioprinting of tissues and organs”, Nat. Biotechnol 2014, vol. 32, pp. 773-785.
Another approach for compact drop-on-demand systems is the piezoelectric actuation, which also allows for the design of compact systems with liquids having similar rheological properties to the ones dispensed by thermal actuation. Piezoelectric-based dispensing systems are based on the generation of a pressure wave by the piezoelectric crystal contained in each chamber, hence pushing outwards a droplet. The drop diameter is also defined by the nozzle diameter. However, it has been shown that sub-nozzle resolution can be achieved by defining a proper cycle of positive and negative pressure waves and tuning the viscosity of the ink. See Chen A U, Basaran O A. “A new method for significantly reducing drop radius without reducing nozzle radius in drop-on-demand drop production” Phys Fluids, 2002, vol. 14, pp. L1-L4.
Several approaches attempted to use light-actuation for drop-on-demand systems, for instance using light to drive the isomerization of surfactants from cis to trans, it was demonstrated that it is possible to dispense droplets on demand by tuning the surface tension of a liquid in suspension. See for example Shin J Y, Abbott N L. “Using light to control dynamic surface tensions of aqueous solutions of water soluble surfactants” Langmuir 1999, vol. 15, pp. 4404-10. The main drawbacks of this method are that the droplet size is only defined by gravity and surface tension, and that the method is limited to specific liquids. Another approach consists in focusing a femtosecond laser pulse on a micrometric spot close to the open surface of a liquid reservoir. Even for weakly absorbing liquids, the tight focusing allows to overcome the optical breakdown threshold, leading to the generation of a transient bubble close to the surface and the generation of a jet. See Duocastella M, Patrascioiu A, Fernández-Pradas J M, Morenza J L, Serra P. “Film-free laser forward printing of transparent and weakly absorbing liquids” Opt. Express, 2010, vol. 18, pp. 21815-25.
The most mature light-assisted drop-on-demand technology is perhaps Laser-assisted Forward Transfer (LIFT) See U.S. Pat. No. 7,014,885. In LIFT, large light transparent ribbons (typically more than 20 mm) are coated with a thin (20 nm-30 nm) solid-state film of metal, such as gold, which is light absorbing. The ribbons are then covered with a thin layer of ink, typically a few tens of microns thick, and set upside down, on top of the receiving substrate. An infrared or ultraviolet nanosecond laser pulse is then focused on a spot on the top of the ribbon. When a sufficient energy is transferred to the light-absorbing film, this film vaporizes the small volume of ink directly in contact with the metal layer that was illuminated. When the laser energy is high enough, the bubble expansion allows for the ejection of at least one droplet towards the substrate. The absence of walls on the ribbon permits to dispense micrometric droplets of highly viscous fluids (1-300 mPa·s). See Guillemot F, Souquet A, Catros S, Guillotin B, Lopez J, Faucon M, et al. “High-throughput laser printing of cells and biomaterials for tissue engineering” Acta Biomater 2010; vol. 6, pp. 2494-2500. It has been demonstrated that the vaporization of the metallic light-absorbing layer results in the contamination of the droplets. This problem can be solved by using a thin micrometric layer of solid-state polymer instead of metal. With proper laser energy, the polymeric layer will generate a blister and dispense droplets. See Brown M S, Kattamis N T, Arnold C B, “Time-resolved study of polyimide absorption layers for blister-actuated laser-induced forward transfer,” Journal of Applied Physics, 2010, vol. 107, p. 3103. However, in LIFT the large ribbons used as ink cartridges makes it impossible for the system to be compact.
More recently, it has been demonstrated that a flow-focusing effect can take place when a light-triggered shockwave impinges on a concave meniscus at the open end of a water-filled micro-capillary. See Tagawa Y, Oudalov N, Visser C W, Peters I R, van der Meer D, Sun C, et al. “Highly Focused Supersonic Microjets,” Phys. Rev. X 2012, vol. 2, p. 031002. High velocity jets and micro-droplets were consequently produced on demand. Furthermore, as a proof of principle, this method was implemented as contactless drug-delivery system. See Tagawa Y, Oudalov N, Ghalbzouri A E, Sun C, Lohse D. “Needle-free injection into skin and soft matter with highly focused microjets,” Lab Chip 2013, vol. 13, pp. 1357-1363. However, this system also lacked of compactness as the laser pulses were delivered by a microscope objective aside of the liquid-filled micro-capillary.
Therefore, despite all the advancements in the fields of micro-droplet generation, ink-jet systems, and drop-on-demand solutions, further improvements are desired to address the drawbacks and issues of the available background art systems that are discussed above.
According to one aspect of the present invention, a device or system is provided that includes a structure and physical mechanism to generate micro-droplets from a liquid-filled delivery system by light-actuation. Preferably, this compact drop-on-demand system allows for liquids with a viscosity between 0.5 mPa·s and 200 mPa·s, but not limited to, to be ejected on demand as single micrometric droplets. The system first includes a micro-delivery system, such as a glass micro-capillary, but not limited to. In at least one embodiment, the inner walls of the system's nozzle are covered with a thin solid-state light-absorbing film. In at least one embodiment, the solid-state light-absorbing film is a metal. In at least one embodiment, an optical fiber or a bundle of optical fibers is enclosed in the delivery system so that a fluid can still flow in the system. The delivery system is filled with a liquid so that the liquid's meniscus is in proximity to the nozzle of the system and, in at least one embodiment part of the liquid is in contact with the light-absorbing film. In at least one embodiment of this invention, the liquid is light absorbing. A pulse of laser light is propagated through a waveguide and a spot or several spots of light are focused onto the light-absorbing film or the liquid. When the energy delivered into a laser spot is high enough, a transient bubble and a shockwave are generated. When the distance between the bubble and the liquid's meniscus is short enough, a flow-focusing effect takes place on the meniscus and one or several droplets of the liquid are ejected along the axis of the nozzle. The meniscus goes back to its initial shape shortly after the droplet breakup and allows for the generation of additional droplets. The solid-state light-absorbing film can be, but not limited to gold or platinum. In at least one embodiment of this invention, the delivery system is a capillary waveguide. Preferably, the laser pulse width can be, but not limited to 5 ns-2 μs. Preferably, the laser pulse energy can be, but not limited to 20 μJ-300 μJ. Preferably, the thickness of the light-absorbing layer can be, but not limited to 10 nm-10 μm. Preferably, the diameter of the capillary can be, but not limited to 10 μm-500 μm. In at least one embodiment, the solid-state light-absorbing film is a polymer, such as Kapton™ polyimide, but not limited to.
Furthermore, in at least one embodiment, an endoscopic drug delivery system is provided that can be actuated by light and the liquid that is discharged can have, but not limited to a biological or drug content. In at least one embodiment, a system and method for printing an article by light-actuation is provided, and the liquid to be discharged can contain, but not limited to, polymers, monomers, solvents and photo-initiators. Preferably, in this embodiment, three-dimensional structures can be printed.
An application example is for delivering a specific amount of drug at a specific location in the eye. According with yet another aspect of the present invention, a method for delivering a drug to a specific location in a body is provided, by using an endoscopic drug delivery system. Such specific location could be at the retina to treat eye diseases, or the brain or teeth or the ear such as in the cochlear. In a further embodiment, the endoscopic delivery system can deliver a polymerizable material to form, for example, but not limited to, a scaffold structure.
The summary of the invention is neither intended nor should it be construed as being representative of the full extent and the scope of the invention, which additional aspects will become more readily apparent from the detailed description, particularly when taken together with the appended drawings.
The accompanying drawings, which are incorporated herein and constitute part of this specification, illustrate the presently preferred embodiments of the invention, and together with the general description given above and the detailed description given below, serve to explain features of the invention.
Herein, identical reference numerals are used, where possible, to designate identical elements that are common to the figures. Also, the images in the drawings are simplified for illustration purposes and may not be depicted to scale.
The techniques, apparatus, materials and systems as described in this specification can be used to implement a compact light-actuated drop-on-demand system. Described is a compact light-actuated liquid dispensing device and system composed of a delivery system, and at least one optical waveguide.
According to another aspect of the present invention, an actuation is proposed with focused spots of light through optical fibers, overcoming several drawbacks of the background solutions. The propose actuation method allows for a compact, light-actuated drop-on-demand system with a sub-nozzle resolution. The device that employs this method is also able to dispense highly viscous liquids. With this method, system, and device, a digital phase conjugation technique can be used for generating a sharp focus point at an end of a multimode optical fiber, for the modulation of optical wavefronts. See Papadopoulos I, Farahi S, Moser C, Psaltis D., “Focusing and scanning light through a multimode optical fiber using digital phase conjugation,” Opt. Express, 2012, vol. 20, pp. 10583-10590.
In at least one embodiment of the present invention, the device can be operated with a light-absorbing liquid as described in
In at least one embodiment of the invention, the device can be operated with a capillary optical waveguide as described in
Furthermore, in at least one embodiment of the device, the delivery system can have, but not limited to, a tapered nozzle as described in
In at least one embodiment of the invention, the device can be operated with a single-mode fiber as a means to create a bubble on the distal tip of the fiber and consequently generate one or more droplets as described in
Lastly, in at least one embodiment of the invention, the device can operate with an imaging system alongside the delivery system in order to control the delivery of the droplets. The imaging device can operate, but not limited to, via an optical fiber collecting the light emitted by a source, as described in
Next, a proof of principle demonstration and measurements for the system and device are presented. As a proof of principle glass micro-capillaries of inner diameter ranging from 100 μm to 420 μm were filled with a non-Newtonian polymeric ink, such as SU-8, methyl methacrylate (MMA), 1,6-hexanediol diacrylate (HDDA), and trimethylpropane triacrylate (TMPTA). The inks were stained with an organic dye having a peak absorption in the green part of the spectrum of light. Furthermore, the inks had solid contents between 0% and 50%, which resulted in viscosities ranging from 0.6 mPa·s to 150 mPa·s. Moreover, due to surface tension, the inks had a contact angle with the micro-capillary's glass interface between 30° and 55°. Stained Newtonian water-glycerol mixtures of viscosities ranging from 2 mPa·s to 210 mPa·s were also used. The Newtonian inks we had a contact angle with the micro-capillary's glass interface between 25° and 35°. By focusing a green laser pulse, with a temporal width of 5 ns, and energy between 3 μJ and 70 μJ, on a spot located in the ink contained in the capillary and close to the walls of the capillaries, a small volume of the ink was vaporized, hence generating a transient bubble. When the distance between the bubble and the meniscus formed by the ink at the open end of the capillary was short enough, for example of the order of a few hundreds of microns, the shockwave generated by the bubble allowed for a flow-focusing effect at the meniscus interface, thereby generating one or more micro-droplets. The results demonstrate that the method can generate single micro-droplet on demand for fluids with a viscosity ranging from 0.6 mPa·s to 148±11 mPa·s for non-Newtonian inks and from 2 mPa·s to 210 mPa·s for the Newtonian inks. The results also demonstrate that the diameter of the single droplet increases with the viscosity of the ink but still remains small compared to the capillary's diameter. The achieved sub-nozzle resolution shows that clogging would therefore not impede the proposed system. Moreover, the velocity of the produced micro-droplets was measured between 0.5 m/s and 5 m/s, the velocity increasing with the energy sent to generate the bubble.
Lastly, to demonstrate that the current method can be used to print structures, a flat glass substrate was placed 2 mm below the distal tip of the capillary and a right-angle pattern, shown in
The design and fabrication of a drop-on-demand apparatus using light actuation through optical fibers have been described. By focusing a spot of laser light through an optical waveguide, such as a multimode optical fiber enclosed in the delivery system, onto a thin light-absorbing layer, a bubble and a shockwave are generated and allow for the ejection of at least one micro-droplet of the liquid. Moreover, this compact delivery system allows for the generation of micro-droplet of fluids with high viscosities. Furthermore, depending on the rheological properties of the liquid, the droplet diameter can range down to one order of magnitude smaller than the capillary's diameter.
While the invention has been disclosed with reference to certain preferred embodiments, numerous modifications, alterations, and changes to the described embodiments are possible without departing from the sphere and scope of the invention, as defined in the appended claims and their equivalents thereof. Accordingly, it is intended that the invention not be limited to the described embodiments, but that it have the full scope defined by the language of the following claims.
Number | Date | Country | Kind |
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PCT/IB2015/055717 | Jul 2015 | IB | international |
The present application claims foreign priority to the PCT filing with the Serial No. PCT/IB2015/055717, filed on Jul. 29, 2015, the entire contents thereof herewith incorporated by reference.