System, apparatuses, devices, and methods for producing particles

Abstract

Embodiments of the present disclosure include, for example, systems, apparatuses, devices, and methods for producing a population of particles. In some embodiments, such particles include particles corresponding to an active, pharmaceutical ingredient.

What is currently claimed: 
     
         1 . A particle generating apparatus for producing a plurality of particles of a predetermined size, the apparatus comprising:
 an atomization means;   a connector;   a drying chamber;   at least one ionizer; and   an electrostatic collector/precipitator.   
     
     
         2 . The apparatus of  claim 1 , further comprising a solution container configured to retain a solution including at least one predetermined dissolved substance at a predetermined concentration, 
     
     
         3 . The apparatus of  claim 1  or  2 , further comprising at least one pump configured to at least one of move the solution from the solution container to the atomization means and return solution to the solution container. 
     
     
         4 . The apparatus of any of  claims 1 - 3 , further comprising a scale configured to monitor solution consumption. 
     
     
         5 . The apparatus of any of  claims 1 - 4 , wherein the atomization means comprises at least one of a pneumatic atomizer and an ultrasonic atomizer, each configured to atomize the solution to produce a droplet flow comprising a plurality of droplets of the solution, wherein, in some embodiments, the ultrasonic atomizer comprises one or more active elements which can be configured to control at least one, and preferably, a plurality of, ultrasonic parameters. 
     
     
         6 . The apparatus of  claim 5 , wherein the atomizer means further comprises at least an inlet configured to provide air for the droplet flow. 
     
     
         7 . The apparatus of  claim 5  or  6 , wherein with respect to the pneumatic atomizer, at least one of a size and/or mass of the droplets and a flowrate thereof is determined by a configuration of the design of the pneumatic atomizer, and/or a driving fluid (e.g., air) flow pressure. 
     
     
         8 . The apparatus of any of  claims 5 - 7 , wherein with respect to the ultrasonic atomizer, at least one of: a size and/or mass of the droplets and a flowrate thereof, is determined by at least one of: one or more ultrasonic parameters comprising temporal and/or spatial modulation of frequency of one or more active elements of the ultrasonic atomizer, either independently or in concert with an ultrasonic actuator, including, for example, harmonic content such as fractional harmonics/subharmonics/super harmonics, amplitude, and/or phase, pulse repetition frequency, acoustic axis, static/dynamic modal patterns (e.g., standing, translating, rotating) on the actuator surface and design of an atomizer vessel. 
     
     
         9 . The apparatus of any of  claims 1 - 8 , wherein the drying chamber is configured to expose the droplet flow to a drying flow so as to produce a dried particle flow having particles of a size and/or mass less than a predetermined threshold size. 
     
     
         10 . The apparatus of any of  claims 1 - 9 , wherein the drying chamber is configured to direct the dried particle flow with particles of a size less than or equal to a predetermined threshold out of the drying chamber via an outlet. 
     
     
         11 . The apparatus of any of  claims 1 - 10 , wherein the drying chamber includes a drying chamber fluid inlet configured to supply fluid (e.g., air) for the drying flow at a regulated flowrate to regulate at least one of the volume of the droplets and volume of dried particles. 
     
     
         12 . The apparatus of any of  claims 1 - 11 , wherein the drying chamber further includes a fan configured to provide a constant pressure to the drying flow, and/or to regulate the level of the feed solution consumption. 
     
     
         13 . The apparatus of any of  claims 1 - 12 , wherein the drying chamber further includes a drying chamber outlet. 
     
     
         14 . The apparatus of any of  claims 1 - 13 , wherein the drying chamber further includes a heater. 
     
     
         15 . The apparatus of any of  claims 1 - 14 , wherein the drying chamber further includes a laminar flow device configured to generate a homogenous drying flow. 
     
     
         16 . The apparatus of any of  claims 1 - 15 , wherein the drying chamber is configured to provide a controlled upward against gravity directed flow of the drying flow so as to dry the received droplet flow to form the plurality of dried particles. 
     
     
         17 . The apparatus of any of  claims 1 - 16 , wherein the drying chamber is configured or further configured such that droplets over a predetermined size and/or mass travel downward against the drying flow. 
     
     
         18 . The apparatus of  claim 17 , wherein the droplets over the predetermined size and/or mass are at least one of collected and disposed of. 
     
     
         19 . The apparatus of any of  claims 1 - 18 , wherein the connector includes a bottom end, a top end, and a conduit connecting the first and second ends. 
     
     
         20 . The apparatus of any of  claims 1 - 19 , wherein the connector includes a connector droplet flow outlet configured to correspond to or otherwise comprises an inlet of the drying chamber. 
     
     
         21 . The apparatus of any of  claims 1 - 20 , wherein the connector is configured such that a/the first end is arranged downstream from a/the second end and receives the droplet flow from the atomization means. 
     
     
         22 . The apparatus of any of  claims 19 - 21 , wherein the conduit includes at least two turns forming at least one corresponding S-bend therebetween. 
     
     
         23 . The apparatus of any of  claims 19 - 22 , wherein the second end includes a/the connector droplet flow outlet. 
     
     
         24 . The apparatus of  claim 23 , wherein the connector outlet is configured to at least one of shape and split the droplet flow into a plurality of flows. 
     
     
         25 . The apparatus of any of  claims 1 - 24 , wherein the at least one ionizer comprises a plurality of ionizers. 
     
     
         26 . The apparatus of any of  claims 1 - 25 , wherein the at least one ionizer is arranged and/or configured to expose the particle flow received from the drying chamber via the drying chamber outlet. 
     
     
         27 . The apparatus of any of  claims 1 - 26 , wherein the at least one ionizer produces a predetermined or preprogrammed pattern of ionized flow of negative ions configured to charge the particles of the particle flow to produce a charged particle flow. 
     
     
         28 . The apparatus of any of  claims 1 - 27 , wherein one or more elements of the electrostatic collector are configured to operate at a predetermined voltage (e.g., a profile in time and/or space). 
     
     
         29 . The apparatus of any of  claims 1 - 28 , wherein one or more elements of the electrostatic collector are configured to receive the charged particle flow. 
     
     
         30 . The apparatus of any of  claims 1 - 29 , wherein one or more elements of the electrostatic collector include a central ground electrode protected by a glass shield or tube, an external cylinder having a wall with a surface at the predetermined voltage, and an electrostatic collector exhaust or outlet. 
     
     
         31 . The apparatus of any of  claims 1 - 30 , wherein the electrostatic collector is configured to deflect, in a predetermined temporal and/or spatial pattern, the incoming charged particles of the charged particle flow towards the surface of the wall. 
     
     
         32 . The apparatus of  claim 31 , wherein the particles form a layer on the surface, wherein the layer, in some embodiments, is spatially structured. 
     
     
         33 . The apparatus of any of  claims 1 - 32 , further comprising an apparatus exhaust filter, or an exhaust assembly comprising a filter, an inlet for receiving remaining flow from the electrostatic collector, and an exhaust or outlet for exhausting remaining flow after exposure of the flow to the filter. 
     
     
         34 . The apparatus of  claim 33 , wherein the apparatus exhaust filter is configured to capture dried particles from a/the electrostatic exhaust that are not collected in the electrostatic collector. 
     
     
         35 . The apparatus of any of  claims 1 - 34 , further comprising an apparatus exhaust arranged to exhaust a remaining flow. 
     
     
         36 . The apparatus of any of  claims 1 - 35 , wherein at least one of the droplet flow, the drying flow, the dried particle flow, and the charged particle flow comprise corresponding fluid (e.g., air) flows. 
     
     
         37 . The apparatus of any of  claims 1 - 36 , wherein the size is selected from the group consisting of between: 10 and 700 nm, 20 and 600 nm, 30 and 500 nm, 40 and 400 nm, and 50 and 350 nm. 
     
     
         38 . The apparatus of any of  claims 1 - 37 , wherein the at least one molecule comprises a protein, a nucleic acid, a carbohydrate, a small molecule embedded in a protein, an excipient, and a salt. 
     
     
         39 . The apparatus of any of  claims 1 - 37 , wherein the at least one predetermined molecule comprises an active pharmaceutical ingredient (API). 
     
     
         40 . The apparatus any of  claims 1 - 39 , wherein a/the heater is configured to create a predetermined or preprogrammed spatial and/or temporal heat gradient inside the drying chamber to a temperature according to a predetermined temperature. 
     
     
         41 . The apparatus any of  claims 12 - 40 , wherein the substantially constant pressure is between 0.0 to −0.30 mbar relative to ambient pressure. 
     
     
         42 . The apparatus of any of  claims 1 - 41 , wherein the ionizer output voltage is constant. 
     
     
         43 . The apparatus of any of  claims 1 - 42 , wherein a flowrate through a/the first air inlet is between 5 and 20 L/min. 
     
     
         44 . The apparatus of any of  claims 2 - 43 , wherein the predetermined dissolved ingredient concentration ranges from 0.1 to 20 g/1 L. 
     
     
         45 . The apparatus of any of  claims 9 - 44 , wherein a flowrate of the drying flow ranges from L/min. 
     
     
         46 . The apparatus of any of  claims 1 - 45 , further comprising an atomization fuselage. 
     
     
         47 . The apparatus of  claim 46 , wherein the atomization fuselage comprises an enclosed and/or airtight container for housing the atomization means. 
     
     
         48 . The apparatus of  claim 46  or  47 , wherein the atomization fuselage includes an inlet configured to receive a designated airflow. 
     
     
         49 . The apparatus of  claim 48 , wherein the atomization fuselage comprises or includes a tube connection is routed through a top, bottom or side thereof. 
     
     
         50 . The apparatus of any of  claims 46 - 49 , wherein the fuselage is configured to direct a least one filtered gas for receipt by the atomization means. 
     
     
         51 . The apparatus of  claim 50 , wherein the at least one gas comprises nitrogen. 
     
     
         52 . The apparatus of any of  claims 46 - 51 , wherein at least one gas is supplied to the atomization means via the atomization fuselage at a controlled rate. 
     
     
         53 . The apparatus of any of  claims 46 - 52 , wherein the atomization fuselage stabilizes the droplet flow by the atomization means. 
     
     
         54 . The apparatus of any of  claims 1 - 53 , wherein the at least one ionizer comprises a multi-element ionizer. 
     
     
         55 . The apparatus of claim any of  claims 1 - 54 , wherein the electrostatic collector/precipitator comprises a multi-element electrostatic collector. 
     
     
         56 . A population of particles produced by the apparatus of any of  claims 1 - 55  having a size selected from the group consisting of between 10 and 700 nm, 20 and 600 nm, 30 and 500 nm, 40 and 400 nm, and 50 and 350 nm. 
     
     
         57 . A population of particles produced by the apparatus of any of  claims 1 - 55  having a size distribution of D50 (corresponding to 160 nm). 
     
     
         58 . A particle generating apparatus for producing a plurality of particles of a predetermined size distribution, the apparatus comprising:
 a solution container configured to retain a solution including at least one predetermined dissolved substance at a predetermined concentration;   at least one pump configured to move the solution from the solution container to the atomization means, and optionally to the solution container;   a scale configured to monitor solution consumption;   atomization means comprising:
 an atomizer vessel, and at least one of a pneumatic atomizer and an ultrasonic atomizer configured to atomize the solution to produce a droplet flow comprising a plurality of droplets of the solution, 
 at least one inlet configured to provide air for the droplet flow to at least aid in propelling the plurality of droplets; 
 wherein, with respect to:
 the pneumatic atomizer, at least one of a size and/or mass of the droplets and a flowrate thereof is determined by a configuration of an atomization nozzle, and/or a driving airflow pressure of the atomization nozzle, 
 the ultrasonic atomizer, at least one of: a size and/or mass of the droplets and a flowrate thereof, is determined by at least one of: one or more ultrasonic parameters comprising temporal and/or spatial modulation of frequency of one or more active elements of the ultrasonic atomizer, 
 either independently or in concert with an ultrasonic actuator, including, for example, harmonic content such as fractional harmonics/subharmonics/super harmonics, amplitude, and/or phase, 
 pulse repetition frequency, acoustic axis, static/dynamic modal patterns (e.g., standing, translating, rotating) on the actuator surface and design of the atomizer vessel; 
 
   a drying chamber, wherein
 the drying chamber is configured to:
 expose the droplet flow to a drying flow so as to produce a dried particle flow having particles of a size and/or mass less than a predetermined threshold size, 
 output the dried particle flow with particles of a size less than or equal to a predetermined threshold, 
 
 the drying chamber including:
 a drying chamber fluid (e.g., air) inlet configured to supply fluid (e.g., air) for the drying flow at a regulated flowrate to regulate at least one of the volume of the droplets, volume of dried particles, and density of the dried particles; 
 a fan/pump configured to provide a predetermined or preprogrammed pressure to the drying flow (which is some embodiments is constant pressure); 
 a drying chamber outlet; 
 a heater configured to regulate a temperature of the drying flow located at a bottom of the drying chamber, and 
 a laminar filter configured to homogenize the drying flow, 
 
 wherein:
 the drying chamber is configured to provide a temporally and spatially controlled upward directed drying flow so as to dry the received droplet flow to form the plurality of dried particles, and 
 droplets over a predetermined size and/or mass travel downward against the drying flow for at least one of collection, and disposal; 
 
   a connector having a bottom end, a top end, a conduit connecting the first and second ends, and a connector fluid (e.g., air) inlet, the connector is configured such that:
 the first end is arranged downstream from the second end and receives the droplet flow from the atomization means; and 
 the second end includes the connector fluid (e.g., air) outlet (drying chamber inlet) configured to at least one of shape and split the droplet flow into a plurality of flows; 
   a plurality of ionizers arranged to expose the particle flow received from the drying chamber via the drying chamber outlet, wherein each of the ionizers produce a predetermined or preprogramed ionized flow of negative ions configured to charge the particles to produce a charged particle flow;   an electrostatic collector having one or more elements, where, in some embodiments, each includes a predetermined temporally controlled voltage, and the electrostatic collector configured to:
 receive the charged particle flow, 
 include a central ground electrode protected by a glass shield/tube, an external cylinder having a wall with a surface at the predetermined temporally controlled voltage, and an electrostatic collector exhaust or outlet, and 
 deflect the incoming charged particles of the charged particle flow towards the surface of the wall, such that, the particles form one or more layers thereon, which in some embodiments, is according to a predetermined or preprogrammed 3D pattern; 
   a filter configured to capture dried particles from the electrostatic exhaust that are not collected in the electrostatic collector; and   an apparatus exhaust arranged to exhaust a remaining flow, wherein the apparatus exhaust can be configured as part of an exhaust assembly which can include the filter.   
     
     
         59 . The apparatus of  claim 58 , wherein the size is selected from the group consisting of between: 10 and 700 nm, 20 and 600 nm, 30 and 500 nm, 40 and 400 nm, and 50 and 350 nm. 
     
     
         60 . The apparatus of  claim 58  or  59 , wherein the at least one predetermined molecule comprises an active pharmaceutical ingredient (API). 
     
     
         61 . The apparatus any of  claims 58 - 60 , wherein the heater is configured to create a predetermined or preprogrammed temporal and/or spatial heat gradient inside the drying chamber to a temperature between 20 and 80 deg. C. 
     
     
         62 . The apparatus any of  claims 58 - 61 , wherein the substantially constant pressure is between 0.0 to −0.30 mbar relative to ambient pressure. 
     
     
         63 . The apparatus of any of  claims 58 - 62 , wherein the ionizer output voltage is constant. 
     
     
         64 . The apparatus of any of  claims 58 - 63 , wherein a flowrate through the first air inlet is between 5 and 20 L/min. 
     
     
         65 . The apparatus of any of  claims 58 - 64 , wherein the predetermined dissolved ingredient concentration ranges from 0.1 to 20 g/L. 
     
     
         66 . The apparatus of any of  claims 58 - 65 , wherein a flowrate of the drying airflow ranges from 50 to 200 L/min. 
     
     
         67 . The apparatus of any of  claims 58 - 66 , wherein the at least one molecule comprises a protein, a nucleic acid, a carbohydrate, a small molecule embedded in a protein, an excipient, and a salt. 
     
     
         68 . The apparatus of any of  claims 58 - 67 , wherein at least one of the droplet flow, the drying flow, the dried particle flow, and the charged particle flow comprise corresponding airflows. 
     
     
         69 . The apparatus of any of  claims 58 - 68 , further comprising an atomization fuselage. 
     
     
         70 . The apparatus of  claim 69 , wherein the atomization fuselage comprises an enclosed and/or airtight container for housing the atomization means. 
     
     
         71 . The apparatus of  claim 69  or  70 , wherein the atomization fuselage includes an inlet configured to receive a designated airflow. 
     
     
         72 . The apparatus of  claim 71 , wherein the atomization fuselage comprises or includes a tube connection that is routed through a top, bottom or side thereof. 
     
     
         73 . The apparatus of any of  claims 69 - 72 , wherein the fuselage is configured to direct at least one filtered gas to the atomization means. 
     
     
         74 . The apparatus of  claim 73 , wherein the at least one gas comprises nitrogen. 
     
     
         75 . The apparatus of  claim 73  or  74 , wherein at least one gas is supplied to the atomization means via the atomization fuselage at a controlled rate. 
     
     
         76 . The apparatus of any of  claims 69 - 75 , wherein the atomization fuselage stabilizes the droplet flow by the atomization means. 
     
     
         77 . A population of particles produced by the apparatus of any of  claims 58 - 76  having a size selected from the group consisting of between: 10 and 700 nm, 20 and 600 nm, 30 and 500 nm, 40 and 400 nm, and 50 and 350 nm. 
     
     
         78 . A population of particles produced by the apparatus of any of  claims 58 - 76  having a size distribution of D50. 
     
     
         79 . A drying chamber device for a particle generating apparatus configured to expose a droplet flow to a drying flow so as to produce a dried particle flow having particles of a size and/or mass and/or density less than a predetermined threshold size. 
     
     
         80 . The device of  claim 79 , the drying chamber comprises a drying chamber air inlet configured to supply air for the drying flow at a regulated flowrate to regulate at least one of the volume of the droplets, volume of dried particles, and density of the dried particles. 
     
     
         81 . The device of  claim 80 , further comprises at least one of a fan/pump configured to provide a constant pressure to the drying flow, a drying chamber outlet, a heater configured to regulate a temperature of the drying flow located at a bottom of the drying chamber, and a laminar filter configured to generate a homogenous drying flow. 
     
     
         82 . The device of  claim 80  or  81 , wherein the drying chamber is configured to provide a controlled upward directed flow of the drying flow so as to dry the received droplet flow to form the plurality of dried particles, and/or droplets over a predetermined size and/or mass travel downward against the drying flow for at least one of collection, and disposal. 
     
     
         83 . A connector device for a particle generating apparatus comprising a bottom end, a top end, a conduit connecting the first and second ends, and a connector air inlet. 
     
     
         84 . The device of  claim 83 , wherein the device is configured such that:
 the first end is arranged downstream from the second end and receives the droplet flow from the atomizer;   the conduit includes at least two turns forming at least one corresponding S-bend; and/or
 the second end includes the connector air inlet configured to at least one of shape and split the droplet flow into a plurality of flows. 
   
     
     
         85 . An electrostatic collector device for a particle generating apparatus comprising a central ground electrode protected by a glass tube, an external cylinder having a wall with a surface at the predetermined voltage. 
     
     
         86 . The device of  claim 85 , wherein the device is arranged with a particle generating device so as to expose a particle flow to an ionized flow of negative ions configured to charge particles in the particle flow to produce a charged particle flow. 
     
     
         87 . An electrostatic collector device for a particle generating apparatus comprising a central ground electrode protected by a glass tube, and an external cylinder having a wall with a surface at the predetermined voltage. 
     
     
         88 . The device of any of  claims 85 - 87 , further comprising an electrostatic collector exhaust. 
     
     
         89 . The device of any of  claims 85 - 88 , wherein the device includes a predetermined voltage. 
     
     
         90 . The device of any of  claims 85 - 89 , wherein the device is configured to receive a charged particle flow. 
     
     
         91 . The device of  claim 90 , wherein the device is configured to deflect incoming charged particles towards the surface of the wall. 
     
     
         92 . The device of  claim 91 , wherein the particles are deflected toward the surface of the wall to form a layer thereon. 
     
     
         93 . A method of producing a population of particles comprising:
 atomizing a solution featuring a dissolved predetermined molecule of a predetermined concentration to produce a plurality of droplets in a droplet flow;   separating the droplets of less than or equal to a threshold size and/or mass in the droplet flow via at least one of:
 gravity and upward flow along a connector, wherein droplets greater than the threshold size and/or mass flow back against the upward flow and are collected re-atomization or discarded, and 
 electrostatic separation; 
   directing or otherwise exposing the droplet flow containing the droplets of less than the threshold size into one or more elevated temperature drying flows, wherein the drying flows provide a controlled upward directed flow of hot air or gas so as to evaporate the droplets to produce a plurality of dried particles in a dried particle flow, wherein particles and/or droplets having a size and/or mass greater than a threshold amount too heavy to be retained in the upward drying airflows, fall down and be discarded (or collected/returned);   charging the dried particles in the dried particle flow with a temporally and/or spatially predetermined or preprogrammed flow of negative ions establishing a charged particle flow; and   deflecting the charged particle flow via an electrostatic collection device comprising one or more elements onto a surface for collection thereof, wherein, in some embodiments, the charged particle flow is deflected onto the surface in a predetermined or preprogrammed pattern.   
     
     
         94 . The method of  claim 93 , wherein the size is selected from the group consisting of between: 10 and 700 nm, 20 and 600 nm, 30 and 500 nm, 40 and 400 nm, and 50 and 350 nm. 
     
     
         95 . The method of  claim 93  or  94 , wherein the at least one predetermined molecule comprises an active pharmaceutical ingredient (API). 
     
     
         96 . The method any of  claims 93 - 95 , wherein the drying flow is at a predetermined temperature. 
     
     
         97 . The method any of  claims 93 - 96 , wherein the drying airflow is provided at a substantially constant pressure between 0.0 to −0.30 mbar relative to ambient pressure. 
     
     
         98 . The method of any of  claims 93 - 97 , wherein the particles are charged via at least one ionizer having a specific output voltage between. 
     
     
         99 . The method of any of  claims 93 - 98 , wherein the provided air for the droplet flow to at least aid in propelling the plurality of droplets is between 5 and 20 L/min. 
     
     
         100 . The method of any of  claims 93 - 99 , wherein the predetermined dissolved ingredient concentration ranges from 0.1 to 20 g/L. 
     
     
         101 . The method of any of  claims 93 - 100 , wherein a flowrate of the drying airflow ranges from 50 to 200 L/min. 
     
     
         102 . The method of any of  claims 93 - 101 , wherein the at least one molecule comprises a protein, a nucleic acid, a carbohydrate, a small molecule embedded in a protein, an excipient, and a salt. 
     
     
         103 . The method of any of  claims 93 - 102 , wherein at least one of the droplet flow, the drying flow, the dried particle flow, and the charged particle flow comprise corresponding airflows. 
     
     
         104 . A system, apparatus, device or method according to any of the disclosed embodiments, or according to one or more elements thereof.