DEVICE AND METHOD FOR PREPARATION OF LIQUID MARBLES

Abstract

A device for preparation of liquid marbles that has a belt conveyor for carrying a layer of solid particles, the belt conveyor being provided, successively in the direction of movement of the belt with at least one solids dispenser with a reservoir for solid particles, at least one liquid dispenser with a reservoir for liquid, and a separator for separating the prepared liquid marbles from solid particles, is disclosed.

Claims

1. A device for preparation of liquid marbles, characterized in that it comprises a belt conveyor (1) for carrying a layer of solid particles, said belt conveyor (1) being provided, successively in the direction of movement of the belt, with at least one solids dispenser (2) with a reservoir for solid particles, at least one liquid dispenser (5) with a reservoir (7) for liquid, and a separator for separating the prepared liquid marbles from solid particles.

2. The device according to claim 1, which further comprises means (4) for adjusting the height of the layer of solid particles, said means being located downstream of the solids dispenser (2); said means (4) being preferably height-adjustable for setting heights of the layer of solid particles within the range of 1 to 20 mm.

3. The device according to claim 1, wherein the solids dispenser (2) is equipped with a mechanical agitator, a rotating disk with blades, or a vibrating wall, for preventing formation of a arching inside the solids dispenser.

4. The device according to claim 1, wherein the liquid dispenser (5) comprises a pump, preferably selected from a syringe pump, a pump with a syringe, a piston in a heated block, a pneumatic pump, a linear pump, a peristaltic pump, a centrifugal pump, a gear pump, a spindle pump, a single-channel or multiple-channel dispense solenoid valve, a diaphragm pump, a vane pump, a pneumatic pump, a hydrostatic pump, a screw pump, and a dosing valve; and/or by the liquid dispenser (5) being height-adjustable.

5. The device according to claim 1, wherein the outlet of the liquid dispenser (5) is a hollow capillary with an inner diameter of 0.05 to 2.5 mm, or a set thereof, or a needle with an inner diameter of 0.1 mm to 0.9 mm with a straight or bevelled tip, or a set thereof.

6. The device according to claim 1, wherein the liquid dispenser (5) is further provided with a system for accurate and rapid droplet formation which vibrates regularly in contact with the dispenser; such system is preferably selected from a diaphragm compressed by a regularly moving piston, a piezoelectric transducer acting on a liquid, a diaphragm compressed by a solenoid with a spring, a device producing an air flow along the dispenser needle, a device causing mechanical vibration of the needle in its longitudinal or transverse direction.

7. The device according to claim 1, wherein the liquid dispenser (5) is further provided with a system for regulating the temperature of the liquid to be dispensed.

8. The device according to claim 1, wherein the belt conveyor (1) is provided with a plurality of solids dispenser and/or with a plurality of liquid dispensers.

9. The device according to claim 1, wherein surface of the belt conveyor (1) belt is made of a material selected from teflonglass fabrics, teflon (polytetrafluoroethylene), silicone, metal, polyvinyl chloride, polyurethane, polyethylene, thermoplastic elastomeric copolymer of polybutylene terephthalate and glycols, rubber, and combination thereof.

10. The device according to claim 1, wherein the belt conveyor (1) is provided with a rake downstream of the liquid dispenser (5), said rake being configured for rolling or rotating of the droplets and completing their coating by solid particles.

11. The device according to claim 1, wherein the belt conveyor (1) is provided with a system for mechanical vibration of the belt located downstream of the liquid dispenser (5).

12. The device according to claim 1, wherein the separator is provided with a sloping stop (9) for carrying solid particles and for completing the coating of liquid marbles.

13. The device according to claim 1, wherein the separator comprises a vibrating screen (8) or a set of vibrating screens, preferably the vibrating screen(s) is/are removable.

14. A method of producing liquid marbles comprising the step of employing the device according to claim 1.

15. A method of producing liquid marbles, said method comprising the steps of: providing the device according to claim 1, continuously applying a layer of solid particles to a moving belt conveyor (1) by means of at least one solids dispenser (2), applying droplets of liquid to this layer by at least one liquid dispenser (5) to at least partially coat the liquid droplets with the said solid particles, optionally rolling or rotating the said liquid droplets to be completely coated to form liquid marbles, transferring the said at least partially coated liquid droplets into a separator in which their coating by solid particles is completed, if needed, to form liquid marbles, separating the produced liquid marbles from the excess solid particles on the basis of their different sizes.

Description

BRIEF DESCRIPTION OF DRAWING

[0039] FIG. 1 shows a device described in Example 1.

EXAMPLES OF CARRYING OUT THE INVENTION

Example 1: Example of a Device

[0040] The device according to this embodiment is schematically shown in FIG. 1. The device comprises a belt conveyor 1 (in one specific embodiment the length of the belt is 1.5 m and the width is 0.155 m, made of polyester), which is provided with a solids dispenser 2 (bevelled block shape, in one specific embodiment having a volume of 4 l, made of polycarbonate) wherein the solids dispenser is filled with solid particles 3. From the solids dispenser, the solid particles are poured evenly onto the belt, the layer height is controlled and the uniformity or desired layer shape is ensured by a straight or perforated stop 4. In the direction of movement of the belt conveyor 1 (downstream), a liquid dispenser 5 (linear pump) is provided, with a dosing needle or a set of needles (one to six needles) and a reservoir 7 (heated block with a volume of 25 ml) containing liquid 6. At the end of the belt conveyor 1 a separator is arranged containing a sloping stop 9 for completing the coating of the liquid marbles. The separator further comprises a vibrating screen 8 for separating the formed liquid marbles from excess solid particles. The mesh size of the screen is 0.5 mm and the screen is made of stainless steel. The remaining (excess) solid particles 11 fall into a container 10 which, when filled, is dumped into the solids dispenser 2. The liquid marbles are then transferred for further processing or packaging, as indicated by arrow 13. Below the belt is a plate 12 collecting solid particles which have not been removed from the belt. This reduces contamination and dustiness. The liquid dispenser is height-adjustable within the range from 1 to 120 mm above the bed of solid particles. The spacing between the needles is 25 mm, and 15 mm from the edge of the belt. The belt velocity is controlled by a potentiometer in the range from 1 to 25 cm/s.

TABLE-US-00001 TABLE 1 Droplet size as dependent on liquid dispenser settings inner droplet diameter generation droplet droplet of needle flow rate frequency size st. dev. volume liquid (mm) (ml/min) (Hz) (mm) (mm) (mm.sup.3) Rubitherm 0.6 7.8 133     1.24 ±  0.02  1.00 RT50 Rubitherm  0.72  1.01 2    2.34 ±  0.01  6.71 RT50 75%  0.25 0.1 9.3 0.7 ±  0.01  0.18 glycerol in water Rubitherm 0.2  0.97 9.8  1.46 ±  0.04  1.65 RT31 PEG 6000  0.27  1.01 4    1.88 ±  0.01  3.47

Example 2: Preparation of Liquid Marbles for Cell Cultivation

[0041] Aqueous solution of medium and cells was placed in a heated stirred liquid reservoir (37° C.), and a peristaltic pump delivered this aqueous solution to the liquid dispenser needle, by means of which individual droplets were formed. The volume of the thus prepared droplets ranged from 5 to 40 mm.sup.3 in various embodiments of this experiment. PTFE (polytetrafluoroethylene) powder (particle size 35 μm) was used to coat the droplets. PTFE was dosed onto the belt from solids reservoir by means of solids disepnser located 3 to 5 mm above the belt, then the bed of solid particles was adjusted with a stop having trapezoidal ridges (the bottom line corresponds to the droplet diameter). The depth of the ridge was 1 to 3 mm and the liquid was dosed into the groove produced by the stop. A rake was placed downstream, in the middle of the length of the belt conveyor. The rake covered the droplet with solid particles, thus coating the entire surface of the droplet. A separator was placed just below the belt so that the powder and liquid marbles did not suffer any damage from the fall. After separating the solid particles by means of a vibrating screen, the individual liquid marbles were transferred to a 96-well plate and placed in a cell culture incubator.

Example 3: Preparation of Oil Liquid Marbles with a Dissolved Active Ingredient

[0042] Various oils were used as liquids. The oils contained or did not contain an active ingredient, and had viscosities in the range of 1 to 550 mPa.Math.s, density of 0.75 to 1.1 g/cm.sup.3 and surface tension from 25 to 40 mN/m. Lactose (particle size 45 μm) was used as solid particles. Lactose was dispensed on the belt conveyor from a solids dispenser which was height-adjustable within the range of 4 to 12 mm. Dripping of the oil with or without an active ingredient was performed by means of linear pump with a syringe as a liquid dispenser. The droplet size ranged from 2 to 40 mm.sup.3 in various embodiments of this experiment. Downstream from the liquid dispenser, in the middle of the length of the belt conveyor, a second solids dispenser with a solids reservoir was placed, which dispensed further lactose solid particles onto the belt, i.e. also onto the droplets, thus coating the droplets from above. A perforated rake was provided downstream from the second solids dispenser, which ensured agitation of the layer of solid particles between the droplets, thus rolling the droplets and completing the coating. Subsequently, the contents of the belt fell into a separator and onto a vibrating screen with a mesh size smaller than the liquid marbles but larger than 45 μm. The separated liquid marbles were transferred for further processing and the solids were poured back into the solids reservoir and reused.

Example 4: Preparation of Liquid Marbles from a Melt Mixture

[0043] A melt mixture with or without an active ingredient was heated a temperature which was 1 to 20° C. above the melting point of the mixture and homogenized, the melt viscosity was in the range of 5 to 1200 mPa.Math.s, the density in the range of 0.7 to 1.3 g/cm.sup.3 and the surface tension in the range of 25 to 45 mN/m. Solid particles of hydroxypropylmethylcellulose, lactose, methylcellulose with varying particle sizes (from 45 to 250 μm) were used to coat the liquid marbles. The solid particles were dispensed from a solids dispenser that was height-adjustable from 1 to 5 mm, and with a straight stop. Dosing of the melt mixture with or without active substance was performed by a heated dispenser with an outlet consisting of a set of needles with a diameter of 0.2 to 0.9 mm. The height-adjustable liquid dispenser allowed to control the temperature and the speed upon impact of the melt mixture onto the bed of solid particles, thus influencing the composition and the amount of particles in the coating. The higher the melt temperature above the melting point, the more solid particles formed the coating. The droplet size ranged from 0.5 to 40 mm.sup.3 in various embodiments of this experiment. At the end of the belt, the mixture of liquid marbles and excess solid particles fell on a sloping stop, where the coating of the liquid marbles was completed. Subsequently, the liquid marbles were separated from the solid particles by a vibrating screen.