Systems and methods for continuous flow reactors for crystallisation in microgravity environments
The system optimizes MAbs crystallization in microgravity by using controlled mixing and flow conditions in a reactor, addressing gravity-induced challenges and enhancing efficiency and suitability for subcutaneous administration.
Patent Information
- Application Number
- PCT/IB2025/054352
- Authority / Receiving Office
- WO · WO
- Patent Type
- Applications
- Current Assignee / Owner
- Priority Date
- 2024-04-26
- Filing Date
- 2025-04-25
- Publication Date
- 2025-10-30
AI Technical Summary
Existing methods for crystallizing monoclonal antibodies (MAbs) on Earth face challenges due to gravity-induced phenomena like sedimentation and convection, which hinder optimal crystallization, making subcutaneous administration difficult and costly.
A system and method for crystallizing substances, such as MAbs, in microgravity environments using a reactor with throttling nodes and controlled mixing conditions to optimize reagent interaction and crystallization, employing pumps and oscillators to manage flow and mixing in a microgravity environment.
Enhances crystallization efficiency by up to 5-10% compared to Earth-based methods, facilitating improved crystallization characteristics and enabling subcutaneous administration of MAbs, reducing healthcare costs and patient discomfort.
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Abstract
Description
SYSTEMS AND METHODS FOR CONTINUOUS FLOW REACTORS FOR CRYSTALLISATION IN MICROGRAVITY ENVIRONMENTSCROSS-REFERENCE TO RELATED APPLICATIONS
[0001] The present application claims the benefit of U.S. Provisional Application No. 63 / 639,562, filed April 26, 2024, which is incorporated by reference herein in its entirety.BACKGROUND
[0002] Cancer is the second leading cause of death globally and has a strong socio-economic impact. Some of the best treatments, such as monoclonal antibodies (MAbs), still have technical challenges and obstacles to widespread usage due to, e.g., their administration method. Intravenous administration (IV) of MAbs has been shown to reduce the quality of life of patients as well as financially burden hospitals. In contrast, subcutaneous administration (SC) can be performed from the comfort of home thereby greatly improving a patient’s treatment response and unclogging health services. For the MAb to be injected via SC, it can be crystallized to avoid technical challenges for treatment response such as high viscosity and injection issues. Unfortunately, Earth-like gravity conditions may not offer optimal crystallization conditions whereas microgravity conditions, such as those in low earth orbit (LEO), can offer more favorable conditions to crystallize proteins and MAbs. Recognized herein is a need for systems and methods that allow for improved MAb crystallization in optimal crystallization conditions.
[0003] Recognized herein is a need for systems and methods that can improve MAb crystallization and crystallization in optimal conditions.SUMMARY
[0004] Provided herein are systems and methods that can improve crystallization of substances, such as MAbs, in optimal microgravity conditions.
[0005] In an aspect, the present disclosure provides a method for crystallizing a substance in a microgravity environment. In some embodiments, the method comprises receiving a plurality of reagents from at least one source into a reactor, wherein the reactor comprises at least one channel with at least a first portion and a second portion for processing the plurality of reagents. In some embodiments, the method comprises contacting the plurality of reagents within the first portion, wherein the first portion comprises a plurality of periodic or non-periodic throttling nodes for optimizing a type of mixing of the plurality of reagents. In some embodiments, the method comprises displacing the plurality of reagents using a first set of conditions when the plurality of reagents are within the first portion, wherein the first set of conditions is sufficient to cause the type of mixing of a subset of the plurality of reagents. In some embodiments, the method comprises contacting the subset of the plurality of reagents within the second portion, wherein thesecond portion comprises a uniform profile for optimizing crystallizing the subset of the plurality reagents using a second set of conditions sufficient to yield a crystallized substance having a set of crystallization characteristics.
[0006] In some embodiments, the method further comprises storing the plurality of reagents in at least one container. In some embodiments, a geometry of the throttling nodes is configured to support the type of mixing.
[0007] In some embodiments, the plurality of reagents comprises a first reagent and a second reagent. In some embodiments, the first reagent comprises a precipitant solution and the second reagent comprises a substance solution. In some embodiments, the precipitant solution comprises a solution of zinc chloride, sodium citrate tribasic dihydrate, acetone, or a combination thereof. In some embodiments, the substance solution comprises a solution of a noncrystallized form or a crystal seed form of the substance. In some embodiments, the noncrystallized form of the substance comprises insulin. In some embodiments, the plurality of reagents further comprises a third reagent, a fourth reagent, or more reagents.
[0008] In some embodiments, the method further comprises pumping the plurality of reagents from the at least one source to the reactor using a set of pumping conditions. In some embodiments, the set of pumping conditions generates a constant flow rate of the plurality of reagents. In some embodiments, the set of pumping conditions generates a variable flow rate of the plurality of reagents. In some embodiments, the first set of conditions generates a constant displacement frequency or a constant displacement amplitude of the plurality of reagents. In some embodiments, the first set of conditions generates a nonconstant displacement frequency or a nonconstant displacement amplitude of the plurality of reagents.
[0009] In some embodiments, the type of mixing is a diffusive mixing of the plurality of reagents. In some embodiments, the type of mixing is a convective mixing of the plurality of reagents. In some embodiments, the type of mixing is a turbulent mixing of the plurality of reagents. In some embodiments, the type of mixing is a convective mixing, a diffusive mixing, or a turbulent mixing of the plurality of reagents.
[0010] In some embodiments, the first set of conditions and / or the second set of conditions accelerate mixing of the plurality of reagents by at least 5% compared to a different set of conditions. In some embodiments, the first set of conditions and / or the second set of conditions accelerate crystallizing of the plurality of reagents by at least 5% compared to a different set of conditions. In some embodiments, the first set of conditions or the second set of conditions improves at least one crystallization characteristic by at least 10% compared to a different set of conditions.
[0011] In some embodiments, the method further comprises detecting a signal from (i) the mixing in the first portion, (ii) the crystallizing in the second portion, or both. In some embodiments, the detecting comprises using an optical instrument to detect the signal.
[0012] In some embodiments, the method further comprises processing the signal to determine the crystallization characteristics. In some embodiments, the method further comprises using one or more containers to store the crystallized substance or unreacted reagents. In some embodiments, the method further comprises autonomously performing the method using a controller. In some embodiments, the method further comprises iteratively adjusting the first set of conditions responsive to detecting a signal associated with the set of crystallization characteristics. In some embodiments, the method further comprises iteratively adjusting the second set of conditions responsive to detecting a signal associated with the set of crystallization characteristics.
[0013] In some embodiments, the microgravity environment is in low earth orbit (LEO), medium earth orbit (MEO), or geostationary Orbit (GEO). In some embodiments, the microgravity environment is in an orbit assigned to or controlled by a country or a jurisdiction, and wherein the country or the jurisdiction is the USA, Europe, Japan, China, the United Kingdom, Russia, or India.
[0014] In some embodiments, the method further comprises transporting the crystallized substance from the microgravity environment to a terrestrial environment or location. In some embodiments, the method further comprises manufacturing a pharmaceutical drug from the crystallized substance in the microgravity environment or a terrestrial environment or location. In some embodiments, the method further comprises processing the crystallized substance in the microgravity environment to yield a pharmaceutical drug, a pre-approved drug, or an agricultural compound. In some embodiments, the method further comprises transporting the pharmaceutical drug from the microgravity environment to a terrestrial environment or location.
[0015] In an aspect, the present disclosure provides a crystalized substance produced by the method disclosed herein.
[0016] In an aspect, the present disclosure provides a system for crystallizing a substance in a microgravity environment. In some embodiments, the system comprises at least one source configured to store a plurality of reagents for providing into a reactor, wherein the reactor comprises at least one channel with a first portion and a second portion for processing the plurality of reagents. In some embodiments, the system comprises a first pump configured to contact the plurality of reagents within the first portion, wherein the first portion comprises a plurality of periodic or non-periodic throttling nodes for optimizing a type of mixing of the plurality of reagents. In some embodiments, the system comprises an oscillator configured to displace the plurality of reagents using a first set of conditions when the plurality of reagents are within thefirst portion, wherein the first set of conditions is sufficient to cause the type of mixing of a subset of the plurality of reagents. In some embodiments, the system comprises a second pump configured to contact the subset of the plurality of reagents within the second portion, wherein the second portion comprises a uniform profile for optimizing crystallizing the subset of the plurality of reagents using a second set of conditions sufficient to yield a crystallized substance having a set of crystallization characteristics.
[0017] In some embodiments, the system further comprises an observation module configured to detect a signal associated with the set of crystallization characteristics using an optical instrument. In some embodiments, the crystallized substance flows from the reactor to the observation module. In some embodiments, the observation module comprises an optical sensor configured to detect the signal when the oscillator is in a condition other than the first set of conditions.
[0018] In some embodiments, the system further comprises a storage container configured to hold the crystallized substance. In some embodiments, the at least one source comprises at least one container. In some embodiments, the plurality of reagents comprises a first reagent and a second reagent. In some embodiments, the first reagent comprises a precipitant solution and the second reagent comprises a substance solution. In some embodiments, the precipitant solution comprises zinc chloride, sodium citrate tribasic dihydrate, acetone, or a combination thereof. In some embodiments, the substance solution comprises a solution of a noncrystallized form of the substance. In some embodiments, the noncrystallized form of the substance comprises insulin.
[0019] In some embodiments, the first pump is configured to generate a constant flow rate of the plurality of reagents. In some embodiments, the first pump is configured to generate a variable flow rate of the plurality of reagents.
[0020] In some embodiments, the oscillator is configured to generate a constant displacement frequency or displacement amplitude of the of the plurality of reagents using the first set conditions. In some embodiments, the oscillator is configured to generate a nonconstant displacement frequency or displacement amplitude of the of the plurality of reagents using the first set of conditions.
[0021] In some embodiments, the type of mixing is a convective mixing, diffusive mixing, or a turbulent mixing of the plurality of reagents. In some embodiments, the second pump is configured to generate a constant flow rate of the plurality of reagents using the second set of conditions. In some embodiments, the second pump is configured to generate a variable flow rate of the plurality of reagents using the second set conditions.
[0022] In some embodiments, the first set of conditions and / or the second set of conditions accelerate mixing of the plurality of reagents by at least 5% compared to a different set of conditions. In some embodiments, the first set of conditions and / or the second set of conditionsaccelerate crystallizing of the plurality of reagents by at least 5% compared to a different set of conditions.
[0023] In some embodiments, the system is positioned in a launch vehicle. In some embodiments, the microgravity environment is in low earth or-bit (LEO), medium earth orbit (MEO), or geostationary Orbit (GEO). In some embodiments, the microgravity environment is in an orbit assigned to or controlled by a country or a jurisdiction, and wherein the country or the jurisdiction is the USA, Europe, Japan, China, the United Kingdom, Russia, or India. In some embodiments, the launch vehicle comprises the system and is configured for travel into the microgravity environment.
[0024] In some embodiments, the first set of conditions and / or the second set of conditions improves at least one crystallization characteristic by at least 5% compared to a different set of conditions. In some embodiments, the system is configured to use a feedback loop to iteratively adjust the first set of conditions responsive to detecting a signal associated with the set of crystallization characteristics.
[0025] In some embodiments, the system is configured to use a feedback loop to iteratively adjust the second set of conditions responsive to detecting a signal associated with the set of crystallization characteristics.
[0026] In some embodiments, the second pump is the first pump.
[0027] In an aspect, the present disclosure provides a kit for use in a microgravity environment. In some embodiments, the kit comprises at least a first reagent and a second reagent.
[0028] In some embodiments, the first reagent comprises a precipitant solution. In some embodiments, the precipitant solution comprises zinc chloride, sodium citrate tribasic dihydrate, acetone, or a combination thereof. In some embodiments, the second reagent comprises a substance solution. In some embodiments, the substance solution comprises a solution of a noncrystallized form or a crystal seed form of the substance. In some embodiments, the noncrystallized form of the substance comprises insulin.
[0029] In an aspect, the present disclosure provides a launch vehicle comprising the kit as disclosed herein. In some embodiments, the launch vehicle further comprises a rocket and a payload comprising the kit.
[0030] In an aspect, the present disclosure provides a kit for synthesizing a substance in a microgravity environment. In some embodiments, the kit comprises at least a first reagent and a second reagent.
[0031] In some embodiments, the first reagent comprises a precipitant solution. In some embodiments, the precipitant solution comprises zinc chloride, sodium citrate tribasic dihydrate, acetone, or a combination thereof. In some embodiments, the second reagent comprises asubstance solution. In some embodiments, the substance solution comprises a solution of a noncrystallized form or a crystal seed form of the substance. In some embodiments, the noncrystallized form of the substance comprises insulin.
[0032] In an aspect, the present disclosure provides a launch vehicle comprising the kit as disclosed herein. In some embodiments, the launch vehicle comprises a rocket and a payload comprising the kit.
[0033] In an aspect, the present disclosure provides a method for transporting the kit as disclosed herein to a microgravity environment. In some embodiments, the method comprises securing the kit to a launch vehicle. In some embodiments, the method comprises launching the launch vehicle to the microgravity environment from a terrestrial environment.
[0034] In some embodiments, the launch vehicle comprises a rocket and a payload. In some embodiments, the payload comprises the kit.
[0035] In some embodiments, the microgravity environment is in low earth orbit (LEO), medium earth orbit (MEO), or geostationary Orbit (GEO). In some embodiments, the payload is in an orbit assigned to or con-trolled by a country or a jurisdiction, and wherein the country or the jurisdiction is the USA, Europe, Japan, China, the United Kingdom, Russia, or India.
[0036] In an aspect, the present disclosure provides a method for transporting a crystallized substance from a microgravity environment. In some embodiments, the method comprises securing the crystallized substance to an entry vehicle. In some embodiments, the method comprises returning the entry vehicle from the microgravity environment to a terrestrial environment.
[0037] In some embodiments, the entry vehicle comprises a payload. In some embodiments, the payload comprises the crystallized substance.
[0038] In some embodiments, the payload is in low earth orbit (LEO), medium earth orbit (MEO), or geostationary Orbit (GEO) prior to returning from the microgravity environment.
[0039] In some embodiments, the payload is in an orbit assigned to or con-trolled by a country or a jurisdiction, and wherein the country or the jurisdiction is the USA, Europe, Japan, China, the United Kingdom, Russia, or India prior to returning from the microgravity environment.
[0040] Additional aspects and advantages of the present disclosure will become readily apparent from the following detailed description, wherein only illustrative embodiments of the present disclosure are shown and described. As will be realized, the present disclosure is capable of other and different embodiments, and its several details are capable of modifications in various obvious respects, all without departing from the present disclosure. Accordingly, the drawings and description are to be regarded as illustrative in nature and not as restrictive.INCORPORATION BY REFERENCE
[0041] All publications, patents, and patent applications mentioned in this specification are herein incorporated by reference to the same extent as if each individual publication, patent, or patent application was specifically and individually indicated to be incorporated by reference. To the extent publications and patents or patent applications incorporated by reference contradict the present disclosure contained in the specification, the specification is intended to supersede and / or take precedence over any such contradictory material.BRIEF DESCRIPTION OF THE DRAWINGS
[0042] The novel features of the present disclosure are set forth with particularity in the appended claims. A better understanding of the features and advantages of the present disclosure will be obtained by reference to the following detailed description that sets forth illustrative embodiments, in which the principles of the present disclosure are utilized, and the accompanying drawings of which:
[0043] FIG. 1 depicts an example continuous flow reactor, in accordance with some embodiments.
[0044] FIG. 2 depicts an example crystallization system, in some embodiments.
[0045] FIG. 3 depicts an example schematic of the pharmaceutical manufacturing unit, integrated with an onboard computer and power system, in accordance with some embodiments.
[0046] FIGs. 4A-4E illustrate an example of the pharmaceutical manufacturing unit exterior from multiple perspectives, in some embodiments. FIG. 4A illustrates a left side view of the pharmaceutical manufacturing unit. FIG. 4B illustrates a right side view of the pharmaceutical manufacturing unit. FIG. 4C illustrates a front side view of the pharmaceutical manufacturing unit. FIG. 4D illustrates a plan view of the pharmaceutical manufacturing unit. FIG. 4E illustrates a perspective view of the pharmaceutical manufacturing unit.
[0047] FIGs. 5A-5I illustrate an example of the pharmaceutical manufacturing unit interior from multiple perspectives in some embodiments. FIG. 5A illustrates a left side view of the pharmaceutical manufacturing unit. FIG. 5B illustrates a right side view of the pharmaceutical manufacturing unit. FIG. 5C illustrates an upside down front view of the pharmaceutical manufacturing unit. FIG. 5D illustrates a front view of the pharmaceutical manufacturing unit. FIG. 5E illustrates a plan view of the pharmaceutical manufacturing unit. FIG. 5F illustrates a perspective view of the pharmaceutical manufacturing unit. FIG. 5G illustrates a secondary perspective view of the pharmaceutical manufacturing unit. FIG. 5H illustrates a perspective view of the pharmaceutical manufacturing unit interior. FIG. 51 illustrates a secondary perspective view of the pharmaceutical manufacturing unit interior.
[0048] FIGs. 6A-6B illustrate the maximum displacement of an example pharmaceutical manufacturing unit in some embodiments, specifically the top portion 6A and interior 6B.
[0049] FIGs. 7A-7F illustrate an example fluid storage unit from multiple perspectives in some embodiments. FIG. 7A illustrates a left side view of the fluid storage unit. FIG. 7B illustrates a right side view of the fluid storage unit. FIG. 7C illustrates plan view of the fluid storage unit. FIG. 7D illustrates a bottom side view of the fluid storage unit. FIG. 7E illustrates a side view of the fluid storage unit. FIG. 7F illustrates a perspective view of the fluid storage unit.
[0050] FIG. 8 illustrates an example reagent bag for a continuous flow reactor, in accordance with some embodiments.
[0051] FIGs. 9A-9F illustrate an example oscillator module from multiple perspectives in some embodiments. FIG. 9A illustrates a left side view of the oscillator module. FIG. 9B illustrates a right side view of the oscillator module. FIG. 9C illustrates a plan view of the oscillator module. FIG. 9D illustrates a bottom side view of the oscillator module. FIG. 9E illustrates an overhead view of the oscillator module. FIG. 9F illustrates a perspective view of the oscillator module.
[0052] FIGs. 10A-10E illustrate a first example reactor in some embodiments. FIG. 10A illustrates a plan view (first side) of the reactor. FIG. 10B illustrates a plan view (top side) of the reactor. FIG. 10C illustrates a plan view (top end) of the reactor. FIG. 10D illustrates a plan view (second side) of the reactor. FIG. 10E illustrates a plan view (bottom side) of the reactor.
[0053] FIGs. 10F-10J illustrate a second example reactor in some embodiments. FIG. 10F illustrates a plan view (first side) of the reactor. FIG. 10G illustrates a plan view (top side) of the reactor. FIG. 10H illustrates a plan view (top end) of the reactor. FIG. 101 illustrates a plan view (second side) of the reactor. FIG. 10J illustrates a plan view (bottom side) of the reactor.
[0054] FIGs. 10K-10O illustrate a third example reactor in some embodiments. FIG. 10K illustrates a plan view (first side) of the reactor. FIG. 10L illustrates a plan view (top side) of the reactor. FIG. 10M illustrates a plan view (top end) of the reactor. FIG. 10N illustrates a plan view (second side) of the reactor. FIG. 100 illustrates a plan view (bottom side) of the reactor.
[0055] FIGs. 10P-10T illustrate a fourth example reactor in some embodiments. FIG. 10P illustrates a plan view (first side) of the reactor. FIG. 10Q illustrates a plan view (top side) of the reactor. FIG. 10R illustrates a plan view (top end) of the reactor. FIG. 10S illustrates a plan view (second side) of the reactor. FIG. 10T illustrates a plan view (bottom side) of the reactor.
[0056] FIG. 10U illustrates an example stack of reactors in some embodiments.
[0057] FIGs. 11A-11F illustrate an example pump module from multiple perspectives in some embodiments. FIG. 11A illustrates a left side view of the pump module. FIG. 11B illustrates a right side view of the pump module. FIG. 11C illustrates a top side view of the pump module.FIG. 11D illustrates a plan view (bottom side) of the pump module. FIG. HE illustrates a plan view of the pump module. FIG. HF illustrates a perspective view of the pump module.
[0058] FIGs. 12A-12E illustrate an example pump module from multiple perspectives in some embodiments. FIG. 12A illustrates a plan view (underside) of the pump module. FIG. 12B illustrates a plan view of the pump module. FIG. 12C illustrates a side view of the pump module. FIG. 12D illustrates a front side view of the pump module. FIG. 12E illustrates a perspective view of the pump module.
[0059] FIGs. 13A-13E illustrate an example payload controller from multiple perspectives in some embodiments. FIG. 13A illustrates a side view of the pump module. FIG. 13B illustrates a left side view of the pump module. FIG. 13C illustrates a right side view of the pump module. FIG. 13D illustrates a plan view (underside) of the pump module. FIG. 13E illustrates a perspective view of the pump module.
[0060] FIG. 14 illustrates an example central controlling unit in some embodiments.
[0061] FIG. 15 illustrates an example valve in some embodiments.
[0062] FIGs. 16A-16B illustrate an example liquid containment configuration, utilizing O-rings and a seal within the pharmaceutical manufacturing unit in some embodiments. FIG. 16A illustrates a perimeter seal of the pharmaceutical manufacturing unit . FIG. 16B illustrates the double O-rings used for containment.
[0063] FIG. 17 illustrates an example liquid containment configuration, utilizing a double O-ring formation in some embodiments.
[0064] FIGs. 18A-18B illustrate an example power data interface (PDI), wherein FIG. 18A illustrates the PDI exterior to the O-ring and FIG. 18B illustrates the PDI interior to the O-ring in some embodiments.
[0065] FIG. 19 illustrates an example temperature logger, or sensor.
[0066] FIG. 20 illustrates an example fluid containment selection method in some embodiments.
[0067] FIG. 21 illustrates an example simplified software system in some embodiments.
[0068] FIG. 22 illustrates an example system housing, in some embodiments.
[0069] FIG. 23 depicts a non-limiting example of a computing device configured to perform methods herein, in some embodiments.
[0070] FIG. 24 depicts a non-limiting example of a web / mobile application provision system configured to perform methods herein, in some embodiments.
[0071] FIG. 25 depicts a non-limiting example of a cloud-based web / mobile application provision system configured to perform methods herein, in some embodiments.
[0072] FIGs. 26A-26B illustrate benefits of continuous flow reactors for crystallization in microgravity environments, in accordance with some embodiments. FIG. 26A illustrates apotential paradigm shift for reduced drug administration costs by at-home administration. FIG. 26B illustrates a comparison between crystallization on Earth against crystallization in microgravity.
[0073] FIG. 27 illustrates an example experimental method of fluid flow, in some embodiments.DETAILED DESCRIPTION
[0074] While various embodiments of the present disclosure have been shown and described herein, such embodiments are provided by way of example only. Numerous variations, changes, or substitutions may occur without departing from the present disclosure. It should be understood that various alternatives to the embodiments of the present disclosure described herein may be employed.Overview
[0075] Proteins are essential for the structure, operation, and control of cells and tissues and therefore, are a great candidate for use as drugs to treat a wide range of diseases, including cancer. The United States of America (USA) and the European Union (EU) have approved more than 100 distinct therapeutic proteins for use in clinical settings (Dimitrov, “Therapeutic proteins.” Therapeutic Proteins: Methods and Protocols (2012): 1-26, which is incorporated by reference herein in its entirety).
[0076] Among the most helpful proteins in the current cancer treatment collection are monoclonal antibodies (MAbs). These are antibodies that are grown in a lab and function like regular antibodies and can, for example, specifically target cancer cells or be used to boost the body’s immune response (e.g., immunotherapy). MAbs offer specificity as an advantage over other anticancer medicines. However, the administrating techniques of an MAb is one of its main drawbacks. Monoclonal antibodies usually require intravenous administration (IV) due to their molecular size. From the standpoint of the patient, it can be painful and uncomfortable, with potential side effects like bleeding, inflammation, and infection. From a clinician's point of view, the process is difficult and time-consuming. It is at least 50% more expensive from a hospital's point of view than alternative administration methods, like subcutaneous administration (Viola et al, “Subcutaneous delivery of monoclonal antibodies: how do we get there?” Journal of controlled release 286 (2018): 301-314, which is incorporated by reference herein in its entirety). In addition to being less hazardous for the patient and requiring fewer re-administrations, subcutaneous injection also saves time, money, and resources for the healthcare system. Furthermore, since this administration method does not call for professional knowledge, therapy can take place closer to the patients, such as neighborhood pharmacies. This approach is at least 50% less expensive for the hospital than intravenous administration (See Viola et al herein).
[0077] For the monoclonal antibody to be administered subcutaneously, its concentration must be high but which also increases viscosity. Generally, high viscosities cause technical issues with drug administration, especially for use in syringes (Basu et al, “Protein crystals for the delivery of biopharmaceuticals.” Expert opinion on biological therapy 4.3 (2004): 301-317, which is incorporated by reference herein in its entirety). Protein crystallization is one of the main ways which allows for high concentrations to be achieved without a marked increase in viscosity. Protein crystals also allow for sustained release, longer shelflife, and less strict storage conditions. On Earth, monoclonal antibodies are hard to crystallize due to their large size, structural complexity, and flexibility (Chen et al, “Biopurification of monoclonal antibody (mAb) through crystallisation.” Separation and Purification Technology 263 (2021): 118358, which is incorporated by reference herein in its entirety).
[0078] However, when gravity is removed from the equation, gravity-induced phenomena that hinder crystal growth, such as sedimentation and convection, are no longer present. Convection has been hypothesized to affect crystal growth by creating a non-constant solvent concentration around the growing crystals (Yamada et al, “Protein crystallization in space and its contribution to drug development.” Handbook of Space Pharmaceuticals. Cham: Springer International Publishing, 2022. 887-912, which is incorporated by reference herein in its entirety). Thus, the gravity-induced phenomena creates a sub-optimal environment, impacting the arrangement of molecules. In orbit, the chemical and mechanical stresses exerted by convection are replaced by diffusion, a slow and concentration-driven process, reducing flow disturbances. Sedimentation also impacts crystal growth by attracting molecules to the bottom of the bioreactor, preventing the growth of certain crystal regions. The sedimentation effect is mitigated in microgravity, improving the shape and size distribution of the crystals (Martirosyan et al, “Tracing transport of protein aggregates in microgravity versus unit gravity crystallization.” npj Microgravity 8.1 (2022): 4, which is incorporated by reference herein in its entirety).
[0079] In-orbit protein crystallization has been conducted for the last 40 years due to its gravitational conditions. Due to the special conditions offered in microgravity, 40% to 50% of all the crystallization experiments delivered more precise structural data, leading to drug discovery for muscular dystrophy, breast cancer, or periodontal disease (See Yamada et al herein). The growing interest in using space for commercial purposes, coupled with a reduction in the cost of launching to Low Earth Orbit by a factor of 20 (Jones, “The recent large reduction in space launch cost.” 48th International Conference on Environmental Systems, 2018, which is incorporated by reference herein in its entirety), suggests that space manufacturing could become a viable option.
[0080] Typical systems and methods for protein crystallization comprise sedimentation as a result of the effect of gravity. Recognized herein is a need for systems and methods that can utilize theunique microgravity environment present in orbit, resulting in improved crystallization and sedimentation.Systems for continuous crystallization in microgravity environments
[0081] In an aspect, disclosed herein is a system for crystallizing a substance in a microgravity environment. In some embodiments, the system comprises at least one source configured to store a plurality of reagents for providing into a reactor. In some embodiments, the reactor comprises at least one channel with a first portion and a second portion for processing the plurality of reagents. In some embodiments, the system comprises a first pump configured to contact the plurality of reagents within the first portion. In some embodiments, the first portion comprises a plurality of periodic or non-periodic throttling nodes for optimizing a type of mixing of the plurality of reagents. In some embodiments, the system comprises an oscillator configured to displace the fluid using a first set of conditions when the plurality of reagents is within the first portion. In some embodiments, the first set of conditions is sufficient to cause mixing of a subset of the plurality of reagents. In some embodiments, the system comprises a second pump configured to contact the subset of the plurality of reagents within the second portion. In some embodiments, the second portion comprises a uniform profile for optimizing crystallizing of the plurality of reagents using a second set of conditions sufficient to yield a crystallized substance having a set of crystallization characteristics.
[0082] For example, FIG. 1 depicts a high-level architecture of the crystallization system (or pharmaceutical manufacturing unit (PMU)). A plurality of reagents is directed from a reagent storage 1 into a fluidic pump. The fluidic pump 2 further directs the reagents to the reactor 4 (microreactor or X-plate). The reagents, after being pumped by the fluidic pump, are displaced by an oscillator 3 (or displacer) allowing for the displaced reagents to mix and interact. After the reagents have mixed, the reagents and formed crystals are further directed to an observation section 5. Finally, the crystallization product is transferred from the observation section to a crystal storage 6.
[0083] For example, FIG. 2 depicts a detailed architecture of the crystallization system for continuous production of protein crystals in a microgravity environment. A plurality of reagents is directed from input bags into a pump module. Within the pump module, the reagents are pumped through a series of junctions within the pump module toward a reactor. During pumping and upon reaching the reactor, an oscillator (or displacer) displaces the reagents within the crystallization system, allowing for the reagents to mix. The mixed reagents are then directed through a flow cell and isolation valve. The mixed reagents are finally directed into an output bag for storage.
[0084] FIG. 3 depicts a detailed architecture of a crystallization system, integrated with an OBC (onboard computer) and power system. Within this system, an FSU (fluid storage unit) houses aplurality of reagents. From the FSU, the reagents flow to a pump module. The pump module further directs the reagents to a reactor (or X-plate), where an oscillator module (or displacer module) interacts with the reagents. The oscillator acts to displace the reagents, allowing the reagents to mix and form crystals. The formed crystals and reagents are then directed to the observation module. After observation, the formed crystals are then directed back to the fluid storage unit, where an output fluid storage is housed. The integrated onboard computer and power system provides a PDI (power data interface), which provides physical connection to the crystallization system by a power and data line. In connection with the PDI, the PDU (power distribution unit) ensures stable power delivery throughout the system by direct power lines to the components of the crystallization system. A CCU (central controlling unit) coordinates and guides the function of the pump module and oscillator, as well as controls the environmental factors. Finally, the PC (payload controller) acts as the central command and control of the crystallization system and interprets the results from the observation module.
[0085] FIGs. 4A-4E depict the crystallization system. The exterior of the PMU is provided, where a left side (FIG. 4A), right side (FIG. 4B), front side (FIG. 4C), plan view (underside) (FIG. 4D), and perspective view (FIG. 4E) are provided. Within the outside containment, the PMU is housed.
[0086] FIGs. 5A-5G depict an exterior of the PMU with the top portion removed, where a left side (FIG. 5A), right side (FIG. 5B), upside down front side (FIG. 5C), front side (FIG. 5D), overhead view (FIG. 5E), perspective view (FIG. 5F), and perspective view (FIG. 5G) are provided. From the interior overhead view of the PMU 500, the following components are highlighted: 510 - Reactor (X-Plates); 520 - Fluid Storage Unit; 530 - Payload Controller; 540 - Power Distribution Unit; 550 - Central Controlling Unit; 560 - Oscillator Module; 570 - Pump Module; 580 - Valves; and 590 - Observation Module. FIGs. 5H-5I depict a PMU interior, shown from a perspective view (FIG. 5H), and perspective view (FIG. 51) of the interior construction.
[0087] In some cases, the pharmaceutical manufacturing unit (PMU) may comprise the entire crystallization system. In some cases, the PMU may comprise a fluid storage unit. In some cases, the PMU may comprise a reagent storage. In some cases, the PMU may comprise an input bag. In some cases, the PMU may comprise a pump. In some cases, the PMU may comprise a fluidic pump. In some cases, the PMU may comprise a pump module. In some cases, the PMU may comprise an oscillator. In some cases, the PMU may comprise an oscillator module. In some cases, the PMU may comprise a displacer. In some cases, the PMU may comprise a reactor module. In some cases, the PMU may comprise a reactor. In some cases, the PMU may comprise an X-plate. In some cases, the PMU may comprise an observation section, or module. In some cases, the PMU may comprise a crystal storage. In some cases, the PMU may comprise an output bag. In somecases, the PMU may comprise a flow cell. In some cases, the PMU may comprise an isolation valve. In some cases, the PMU may comprise an onboard computer and power system. In some cases, the onboard computer and power system may comprise a payload controller (PC), central controlling unit (CCU), power distribution unit (PDU), or power data interface (PDI). In some cases, the PMU may comprise valves, lines, fittings (including Luer tapers), sensors, traps, pumps, valves, and junctions. In some cases, the PMU may comprise a seal. In some cases, the PMU may comprise an O-ring, as shown in FIG. 16A and 16B. In some cases, the PMU may comprise fasteners, such as screws and bolts.
[0088] In some cases, the PMU may be constructed from a structural material. In some cases, the structural material can comprise any suitable material. In some cases, the structural material can comprise a metal, a metalloid, a nonmetal, derivatives thereof, or combinations thereof. In some cases, the structural material may be a metal. In some cases, the structural material may be an alloy. In some cases, the structural material may comprise any suitable metal, including, but not limited to, Ag, Al, Au, Bi, C, Cr, Cu, Fe, Mg, Mn, Ni, Pb, Sb, Sn, and Zn. In some cases, the structural material may be steel. In some cases, the structural material may be aluminum. In some cases, the structural material may be machined aluminum. In some cases, the structural material may be plastic. In some cases, the structural material may be polycarbonate. In some cases, the structural material may be polyimide. In some cases, the structural material may be polyether etherketone (PEEK). In some cases, the structural material may be Teflon (PTFE). In some cases, the structural material may be polyethylene. In some cases, the structural material may be thermoplastic. In some cases, the structural material may be acetal. In some cases, the structural material may be an epoxy resin. In some cases, the structural material may be polypropylene. In some cases, the structural material may be a fiber metal laminate. In some cases, the structural material may be a polymer matrix composite. In some cases, the structural material may be a ceramic matrix composite. In some cases, the structural material may be a metal matrix composite. In some cases, the structural material may be carbon fiber. In some cases, the structural material may be silicon carbide. In some cases, the structural material may be fiberglass. In some cases, the structural material may be coated. In some cases, the coating may be a protective coating. In some cases, the coating may be anodized protective coating. In some cases, the coating may be configured to reduced corrosion.
[0089] In some cases, the material may be selected to comply with European Space Agency (ESA) structural standards. In some cases, the material may be selected to comply with NASA structural standards. In some cases, compliance may be determined by a structural analysis, leak testing, pressure testing, material compatibility, and vibration testing. In some cases, the material may allow for maximum displacement as a result of pressure. In some cases, the maximumdisplacement of the lid due to pressure may be about 5 millimeters (mm) (FIG. 6A). In some cases, the maximum displacement of the interior due to pressure may be about 2.5 mm (FIG. 6B). In some cases, the material may be selected for its strength. In some cases, the material may be durable. In some cases, the material may be selected to securely house the PMU modules. In some cases, the material may be selected to protect the PMU modules. In some cases, the material may be selected to stabilize the PMU modules.
[0090] In some cases, the PMU may be constructed to provide containment. In some cases, the PMU containment may provide fluid containment. In some cases, the PMU containment may follow a containment levels strategy. In some cases, the PMU containment may be 3 levels of containment. In some cases, a level of fluid containment may be the crystallization system. In some cases, a level of fluid containment may be PMU exterior material. In some cases, a level of fluid containment may be seals along the PMU exterior openings. In some cases, two 2-mm O- rings are utilized. In some cases, a level of fluid containment may be seals to secure a PMU lid to the PMU exterior. In some cases, a 1.5 mm groove and clamping bolts are utilized. In some cases, the fluid containment may be selected based on a system testing method, as shown in FIG. 20.
[0091] In some cases, the seals may be a single seal. In some cases, the seals may be a plurality of seals. In some cases, the seals may be two seals. In some cases, the seals may be three seals. In some cases, the seals may be four seals. In some cases, the seals may be more than four seals. In some cases, the seals may be a single O-ring. In some cases, the seals may be a plurality of O- rings. In some cases, the seals may be two O-rings. In some cases, the seals may be three O-rings. In some cases, the seals may be four O-rings. In some cases, the seals may be more than four O- rings.
[0092] In some cases, the PMU may have a mass. In some cases, the PMU mass may be from about 1 kilogram (kg) to about 200 kg. In some cases, the PMU may be from about 1 kg to about 10 kg. In some cases, the PMU may be from about 10 kg to about 25 kg. In some cases, the PMU may be from about 25 kg to about 50 kg. In some cases, the PMU may be from about 50 kg to about 75 kg. In some cases, the PMU may be from about 75 kg to about 100 kg. In some cases, the PMU may be from about 100 kg to about 125 kg. In some cases, the PMU may be from about 125 kg to about 150 kg. In some cases, the PMU may be from about 150 kg to about 175 kg. In some cases, the PMU may be from about 175 kg to about 200 kg. In some cases, the PMU may be around 5 kg. In some cases, the PMU may be around 50 kg. In some cases, the PMU may be around 100 kg. In some cases, the PMU may be around 150 kg.
[0093] In some cases, the PMU may have a length. In some cases, the PMU length may be from about 10 centimeters (cm) to about 300 cm. In some cases, the PMU length may be from about 10 cm to about 50 cm. In some cases, the PMU length may be from about 50 cm to about 100 cm. Insome cases, the PMU length may be from about 100 cm to about 150 cm. In some cases, the PMU length may be from about 150 cm to about 200 cm. In some cases, the PMU length may be from about 200 cm to about 250 cm. In some cases, the PMU length may be from about 250 cm to about 300 cm. In some cases, the PMU length may be from about 30 cm to about 40 cm. In some cases, the PMU length may be about 36 cm. In some cases, the PMU length may be about 36.9 cm.
[0094] In some cases, the PMU may have a width. In some cases, the PMU width may be from about 10 cm to about 300 cm. In some cases, the PMU width may be from about 10 cm to about 50 cm. In some cases, the PMU width may be from about 50 cm to about 100 cm. In some cases, the PMU width may be from about 100 cm to about 150 cm. In some cases, the PMU width may be from about 150 cm to about 200 cm. In some cases, the PMU width may be from about 200 cm to about 250 cm. In some cases, the PMU width may be from about 250 cm to about 300 cm. In some cases, the PMU width may be from about 20 cm to about 40 cm. In some cases, the PMU width may be about 23 cm. In some cases, the PMU width may be about 23.8 cm.
[0095] In some cases, the PMU may have a height. In some cases, the PMU height may be from about 1 cm to about 300 cm. In some cases, the PMU height may be from about 1 cm to about 50 cm. In some cases, the PMU height may be from about 50 cm to about 100 cm. In some cases, the PMU height may be from about 100 cm to about 150 cm. In some cases, the PMU height may be from about 150 cm to about 200 cm. In some cases, the PMU height may be from about 200 cm to about 250 cm. In some cases, the PMU height may be from about 250 cm to about 300 cm. In some cases, the PMU height may be from about 10 cm to about 30 cm. In some cases, the PMU width may be about 13 cm. In some cases, the PMU height may be about 13.7 cm.
[0096] In some cases, the PMU may operate in different modes. In some cases, the PMU may operate in standby mode, where only essential components are powered. In some cases, the PMU may operate in filling / flushing modes, where the fluids are introduced into the system. In some cases, the PMU may operate in experimental mode, where the PMU is operating at full capacity. In some cases, the PMU may operate in imaging mode, where the pump and oscillator are turned off to allow for undisturbed imaging. In some cases, the PMU may operate in data mode, where experimental data may be downloaded.
[0097] FIG. 22 depicts a larger system housing, wherein the PMU and other components may be housed. In some cases, the larger system may comprise a plurality of PMUs. In some cases, the larger system may comprise a plurality of PMUs, operating in parallel. In some cases, the larger system may comprise a plurality of PMUs, operating in series. In some cases, the larger system may comprise one PMU. In some cases, the larger system may comprise two PMUs. In some cases, the larger system may comprise two PMUs, operating in parallel. In some cases, the larger system may comprise two PMUs, operating in series. In some cases, the larger system maycomprise a more than two PMUs. In some cases, the larger system may comprise an internal computer. In some cases, the larger system may comprise internal organization units, such as shelves or pockets. In some cases, the larger system may comprise a door for internal access. In some cases, the door may be a sliding or hinged door. In some cases, the door may comprise a sliding or hinged secondary access point. In some cases, the larger system may comprise a temperature control system. In some cases, the larger system may comprise a heating system. In some cases, the larger system may comprise a cooling system. In some cases, the larger system may comprise cooling inlets. In some cases, the larger system may comprise a plurality of cooling inlets. In some cases, the larger system may comprise at least one cooling inlet. In some cases, the larger system may comprise at least two cooling inlets. In some cases, the larger system may comprise at least three cooling inlets. In some cases, the larger system may comprise at least four cooling inlets. In some cases, the larger system may comprise at least five cooling inlets. In some cases, the larger system may comprise a plurality of cooling inlets on each side of the system. In some cases, the larger system may comprise at least one cooling inlet on each side of the system. In some cases, the larger system may comprise at least two cooling inlets on each side of the system. In some cases, the larger system may comprise at least three cooling inlets on each side of the system. In some cases, the larger system may comprise at least four cooling inlets on each side of the system. In some cases, the larger system may comprise at least five cooling inlets on each side of the system.
[0098] In some cases, the selected environment may be a microgravity environment. In some cases, the selected environment may be in low earth orbit (LEO). In some cases, selected environment may be in medium earth orbit (MEO). In some cases, the selected environment may be in geostationary orbit (GEO). In some cases, the selected environment may be in lunar orbit.
[0099] In some cases, the microgravity environment may be in a position in orbit. In some cases, the microgravity environment may be in a position in orbit assigned to or controlled by a country. In some cases, the microgravity environment may be in a position in orbit assigned to or controlled by a jurisdiction. In some embodiments, the microgravity environment is in an orbit assigned to or controlled by a country or a jurisdiction, and wherein the country or the jurisdiction is the USA, Europe, Japan, China, the United Kingdom, Russia, or India. In some cases, the microgravity environment may be in a position in orbit assigned to or controlled by the United States. In some cases, the microgravity environment may be in a position in orbit assigned to or controlled by the United Kingdom. In some cases, the microgravity environment may be in a position in orbit assigned to or controlled by Europe. In some cases, the microgravity environment may be in a position in orbit assigned to or controlled by China. In some cases, the microgravity environment may be in a position in orbit assigned to or controlled by Japan. In some cases, the microgravityenvironment may be in a position in orbit assigned to or controlled by India. In some cases, the microgravity environment may be in a position in orbit assigned to or controlled by Russia. In some cases, the microgravity environment may be in a position in orbit assigned to or controlled by the African Union, Algeria, Argentina, Australia, Austria, Azerbaijan, Bangladesh, Belgium, Brazil, Bulgaria, Canada, Chile, Costa Rica, Czechia, Denmark, Egypt, El Salvador, Ethiopia, France, Germany, Ghana, Greece, Hungary, Indonesia, Iran, Israel, Italy, Kazakhstan, Kenya, South Korea, CELAC, Lithuania, Luxembourg, Malaysia, Mexico, Mongolia, Morocco, Netherlands, New Zealand, Nigeria, Norway, Pakistan, Paraguay, Peru, Philippines, Poland, Portugal, Romania, Rwanda, Saudi Arabia, Singapore, South Africa, Spain, Sweden, Switzerland, Syria, Taiwan, Thailand, Tunisia, Turkey, Turkmenistan, Ukraine, UAE, United Nations, Uzbekistan, Venezuela, or Vietnam. In some cases, the microgravity environment may be on the moon or in an orbit of the moon. In some cases, the microgravity environment may be in a position in orbit assigned to or controlled by any nation with space capability. In some cases, the microgravity environment may be in a position in orbit assigned to or controlled by any nation. In some cases, the microgravity environment may be in a position in orbit assigned to or controlled by another planet.Fluid Storage Unit
[0100] In some embodiments, the at least one source may comprise at least one internal container, or fluid storage unit. In some embodiments, the plurality of reagents may comprise a first reagent and a second reagent. In some embodiments, the first reagent may comprise a precipitant solution and the second reagent comprises a substance solution. In some embodiments, the precipitant solution may comprise a solution of zinc chloride, sodium citrate tribasic dihydrate, acetone, or a combination thereof. In some embodiments, the substance solution may comprise a solution of a noncrystallized form or a crystal seed form of the substance. In some embodiments, the noncrystallized form of the substance may comprise insulin.
[0101] FIGs. 7A-7F depict a fluid storage unit. The fluid storage unit is provided, where a left side (FIG. 7A), right side (FIG. 7B), top side (FIG. 7C), bottom side (FIG. 7D), overhead view (FIG. 7E), and perspective view (FIG. 7F) are provided.
[0102] In some cases, the fluid storage unit (FSU) may be a source. In some cases, the FSU may be a plurality of sources. In some cases, the PSU may be at least one source. In some cases, the FSU may be at least two sources. In some cases, the FSU may comprise an input. In some cases, the FSU may comprise an input bag. In some cases, the FSU may comprise a plurality of input bags. In some cases, the FSU may comprise at least one input bag. In some cases, the FSU may comprise at least two input bags. In some cases, the FSU may comprise at least three input bags. In some cases, the FSU may comprise a number of input bags equal to the number of reagents. Insome cases, the FSU may comprise a case. In some cases, the FSU may comprise fasteners, such as screws and bolts.
[0103] In some cases, the FSU may be configured to house fluid. In some cases, the FSU may be configured to house the reagents. In some cases, the reagents may be a plurality of reagents. In some cases, the reagents may be two reagents. In some cases, the reagents may be three reagents. In some cases, the reagents may be three or more reagents. In some cases, the reagents may be four or more reagents. In some cases, the reagent may be a first reagent. In some cases, the reagent may be a second reagent. In some cases, the reagent may be a precipitant solution. In some cases, the precipitant solution may comprise an organic solvent. In some cases, the precipitant solution may be an aqueous solution. In some cases, the precipitant solution may comprise a salt solution, such as KC1, NaCl, NaCCh, BaCh, CaCh, NaNCh, Na2SO3, Na2S2O3, AgNO2, ZnBr2, or ZnCl2. In some cases, the precipitant solution may comprise a salt. In some cases, the precipitant solution may comprise water. In some cases, the precipitant solution may comprise sodium citrate tribasic. In some cases, the precipitant solution may comprise any suitable components. In some cases, the reagent may be a substance solution. In some cases, the substance solution may comprise an organic solvent. In some cases, the substance solution may be an aqueous solution. In some cases, the substance solution may comprise any suitable components. In some cases, the substance solution may comprise an acid. In some cases, the substance solution may comprise an acid, such as HC2H3O2, H3BO3, CH2O3, H3C6H5O7, HC1, HF, HNO3, H2C2O4, H3PO4and H2SO4. In some cases, the substance solution may comprise water. In some cases, the substance solution may comprise a target substance. In some cases, the substance solution may comprise a target protein substance. In some cases, the substance solution may comprise a noncrystallized form of the target substance. In some cases, the substance may comprise a crystal seed form of the target solution. The substance solution may comprise a target. In some cases, the target may be a product. In some cases, the target may be a pharmaceutical drug. In some cases, the target may be a pre-approved compound. In some cases, the target may be a precursor material. In some cases, the target may be an agricultural substance. In some cases, the target may be a seed of the target. In some cases, the target may be a protein-based drug. In some cases, the target may be a peptide drug. In some cases, the target may be a small peptide drug. In some cases, the target may be an antibody drug conjugate. In some cases, the target may be a GLP-1. In some cases, the target may be an antibody. In some cases, the target may be, for example, pembrolizumab, infliximab, rituximab, or any other antibody. In some cases, the target may be a hormone, such as human growth hormone. In some cases, the target may be an antibody, hormone, or a seed thereof. In some cases, the target may be a seed of a drug. In some cases, the target comprises insulin. In some cases, the uncrystallized or seed for, may comprise insulin. In some cases, the target may be selected based on a selecteddisease or condition. In some cases, the target may be selected for an autoimmune disease. In some cases, the target may be selected for a respiratory infection. In some cases, the target may be selected for a genetic disorder. In some cases, the target may be selected due to its formulation, such as IV, oral, or parenteral. In some cases, the target may be selected due to its thermal stability. In some cases, the target may be selected due to its strong thermal stability. In some cases, the target may be selected due to its poor thermal stability in standard formulations. In some cases, the target may be selected to improve stability. In some cases, the target may be selected due to its release rate. In some cases, the condition may be cancer.
[0104] In some cases, the FSU may be configured to protect internal input bags. In some cases, the input bags may be configured to be chemically stable. In some cases, the input bags may be plastic. In some cases, the input bag may be polyurethane. In some cases, the input bags may be further housed in a shell. In some cases, the shell may be plastic.
[0105] In some cases, the FSU may comprise a case. In some cases, the case can comprise a metal, a metalloid, a nonmetal, derivatives thereof, or combinations thereof. In some cases, the case may be a metal. In some cases, the case may be an alloy. In some cases, the case may comprise any suitable metal, including, but not limited to, Ag, Al, Au, Bi, C, Cr, Cu, Fe, Mg, Mn, Ni, Pb, Sb, Sn, and Zn. In some cases, the case may be steel. In some cases, the case may be aluminum. In some cases, the case may be plastic. In some cases, the case may be polycarbonate. In some cases, the case may be polyimide. In some cases, the case may be polyether etherketone (PEEK). In some cases, the case may be Teflon (PTFE). In some cases, the case may be polyethylene. In some cases, the case may be thermoplastic. In some cases, the case may be acetal. In some cases, the case may be an epoxy resin. In some cases, the case may be polypropylene. In some cases, the case may be a fiber metal laminate. In some cases, the case may be a polymer matrix composite. In some cases, the case may be a ceramic matrix composite. In some cases, the case may be a metal matrix composite. In some cases, the case may be carbon fiber. In some cases, the case may be silicon carbide. In some cases, the case may be fiberglass. In some cases, the case may comprise a polymer. In some cases, the case may be Acrylonitrile Butadiene Styrene (ABS).
[0106] In some cases, the FSU may include an input bag. In some cases, the input bag may be a flexible fluid container. In some cases, the input bag may house at least one reagent. In some cases, the at least one reagent may be passed from the input bag. In some cases, the input bag may pass the at least one reagent via a fluid connection, such as a tube. In some cases, the fluid connection may be integrated with a connector. In some cases, the connector may be a coupler. In some cases, the connector may be configured for fluid replacement. In some cases, the connector may be configured for input bag replacement. In some cases, the connector may be configured for fluid refill. In some cases, the connector may be configured for input bag refill. In some cases, theconnector may be connected to the crystallization system. In some cases, the connector may be connected to a secondary fluid connection, such as a tube, wherein the secondary fluid connection may be connected to the crystallization system. In some cases, the secondary fluid connection may be configured to flow the at least one reagent to the crystallization system.
[0107] In some cases, the input bag may be similar to an IV bag (FIG. 8). In an IV bag-like setup, a reagent may have housed in an IV bag 1. To pass the reagents from the IV bag, an IV bag tube 2 is connected from the IV bag 1. The IV bag tube is integrated with a quick connect coupling 3. The quick connect coupling allows for the IV bags to be replaced or refilled as needed. The coupling connection is further in contact with a tube 4 to allow the reagents to flow to the rest of the crystallization system.
[0108] In some cases, the FSU may be configured to comply with ESA structural standards. In some cases, the FSU may be configured to comply with NASA structural standards. In some cases, the FSU may be deemed acceptable after a leak testing, bag testing, material compatibility, and vibration testing. In some cases, the FSU may be configured to comply with pharmaceutical regulatory standards. In some cases, the FSU may be configured to comply with International Organization for Standardization (ISO) and / or Good Manufacturing Practice (GMP) standards. In some cases, the other PMU components may be configured to comply with the above standards.
[0109] In some cases, the FSU may have a mass. In some cases, the FSU may have a dry mass, where the FSU is not currently housing a reagent. In some cases, the FSU dry mass may be from about 0.1 kg to about 15 kg. In some cases, the dry mass may be from about 0.1 kg to about 1 kg. In some cases, the dry mass may be from about 1 kg to about 2 kg. In some cases, the dry mass may be from about 2 kg to about 3 kg. In some cases, the dry mass may be from about 3 kg to about 4 kg. In some cases, the dry mass may be from about 4 kg to about 5 kg. In some cases, the dry mass may be from about 5 kg to about 10 kg. In some cases, the dry mass may be from about 10 kg to about 15 kg. In some cases, the dry mass may be from about 0.3 kg to about 0.8 kg. In some cases, the dry mass may be about 0.4 kg. In some cases, the dry mass may be about 10 kg. In some cases, the FSU may have a wet mass, where the FSU is housing a reagent. In some cases, the FSU wet mass may be from about 0.1 kg to about 75 kg. In some cases, the wet mass may be from about 0.1 kg to about 1 kg. In some cases, the wet mass may be from about 1 kg to about 2 kg. In some cases, the wet mass may be from about 2 kg to about 3 kg. In some cases, the wet mass may be from about 3 kg to about 4 kg. In some cases, the wet mass may be from about 4 kg to about 5 kg. In some cases, the wet mass may be from about 5 kg to about 10 kg. In some cases, the wet mass may be from about 10 kg to about 20 kg. In some cases, the wet mass may be from about 20 kg to about 30 kg. In some cases, the wet mass may be from about 30 kg to about 40 kg. In some cases, the wet mass may be from about 40 kg to about 50 kg. In some cases, the wet massmay be from about 50 kg to about 60 kg. In some cases, the wet mass may be from about 60 kg to about 70 kg. In some cases, the wet mass may be from about 70 kg to about 75 kg. In some cases, the wet mass may be from about 0.3 kg to about 0.8 kg. In some cases, the wet mass may be about 0.6 kg. In some cases, the wet mass may be about 30 kg. In some cases, the wet mass may be about 40 kg.
[0110] In some cases, the FSU may have a length. In some cases, the FSU length may be from about 10 millimeters (mm) to about 1000 mm. In some cases, the FSU length may be from about 10 mm to about 250 mm. In some cases, the FSU length may be from about 250 mm to about 500 mm. In some cases, the FSU length may be from about 500 mm to about 750 mm. In some cases, the FSU length may be from about 750 mm to about 1000 mm. In some cases, the FSU length may be from about 50 mm to about 150 mm. In some cases, the FSU length may be from about 150 mm to about 250 mm. In some cases, the FSU length may be about 199 mm. In some cases, the FSU length may be about 209 mm.[OHl] In some cases, the FSU may have a width. In some cases, the FSU width may be from about 10 mm to about 1000 mm. In some cases, the FSU width may be from about 10 mm to about 250 mm. In some cases, the FSU width may be from about 250 mm to about 500 mm. In some cases, the FSU width may be from about 500 mm to about 750 mm. In some cases, the FSU width may be from about 750 mm to about 1000 mm. In some cases, the FSU width may be from about 50 mm to about 150 mm. In some cases, the FSU width may be about 67 mm.
[0112] In some cases, the FSU may have a height. In some cases, the FSU height may be from about 10 mm to about 1000 mm. In some cases, the FSU height may be from about 10 mm to about 250 mm. In some cases, the FSU height may be from about 250 mm to about 500 mm. In some cases, the FSU height may be from about 500 mm to about 750 mm. In some cases, the FSU height may be from about 750 mm to about 1000 mm. In some cases, the FSU height may be from about 50 mm to about 150 mm. In some cases, the FSU height may be about 108 mm.
[0113] In some cases, the source, or FSU, may be internal to the system. In some cases, the source, or FSU, may be external to the system.
[0114] In some cases, the crystallization system may be configured to direct the final product into the FSU. In some cases, the FSU may be configured to store the produced crystals. In some cases, the FSU may comprise an output bag. In some cases, the FSU may comprise a plurality of output bags. In some cases, the FSU may comprise one output bag. In some cases, the FSU may comprise two output bags. In some cases, the FSU may comprise three output bags. In some cases, the FSU may comprise three or more output bags.Oscillator Module
[0115] In some embodiments, the oscillator (or displacer) may be configured to generate a constant displacement frequency or displacement amplitude of the fluid using the first set conditions. In some embodiments, the oscillator may be configured to generate a nonconstant displacement frequency or displacement amplitude of the fluid using the first set of conditions. In some embodiments, the type of mixing may be a diffusive mixing of the plurality of reagents.
[0116] FIGs. 9A-9F depict an oscillator module (or displacer module). The oscillator module is provided, where a left side (FIG. 9A), right side (FIG. 9B), top side (FIG. 9C), bottom side (FIG. 9D), overhead view (FIG. 9E), and perspective view (FIG. 9F) are provided. In some cases, the oscillator may be mounted to the system. In some cases, the oscillator may comprise screws / bolts. In some cases, the screws / bolts may be steel. In some cases, the oscillator may comprise electronic components.
[0117] In some cases, the oscillator may be configured to be a level of containment of the enclosed fluids. In some cases, the oscillator may be configured to withstand extended periods of oscillatory motion. In some cases, the oscillator may be configured to withstand periodic periods of oscillatory motion. In some cases, the oscillator may be configured for durability, wherein the oscillator can withstand oscillation without failure.
[0118] In some cases, the oscillator module may be designed to generate motion within the system. In some cases, the oscillator module may be designed to generate oscillatory motion. In some cases, the oscillator module may be designed to generate turbulent motion. In some cases, the motion may be consistent. In some cases, the motion may be repeatable. In some cases, the motion may be relative to the desired experiment. In some cases, the motion of the oscillator may be under a first set of conditions, wherein the conditions may relate to force created or fluid displacement. In some cases, the motion of the oscillator may be under a second set of conditions, wherein the conditions may relate to force created or fluid displacement.
[0119] In some cases, the oscillator may comprise an actuator (or displacer). In some cases, the oscillator may comprise a rotary actuator. In some cases, the oscillator may comprise a special actuator. In some cases, the oscillator may comprise a linear actuator. In some cases, the oscillator may comprise a hydraulic actuator. In some cases, the oscillator may comprise a pneumatic actuator. In some cases, the oscillator may comprise an electric actuator. In some cases, the oscillator may comprise a solenoid actuator. In some cases, the oscillator may comprise an electric motor. In some cases, the oscillator may comprise a piezoelectric actuator. In some cases, the oscillator may comprise a mechanical actuator. In some cases, the oscillator may comprise a thermal actuator. In some cases, the oscillator may comprise a manual actuator. In some cases, the actuator may be of coreless motor design. In some cases, the actuator may be configured to reduce electromagnetic interference generation. In some cases, the actuator may be configured to complywith electromagnetic interference testing. In some cases, the actuator may be configured to reduce interference with other systems. In some cases, the actuator may be configured to reduce interference with nearby, parallel systems.
[0120] In some cases, the actuator may move laterally. In some cases, the actuator may move from about 10 mm to about 50 mm. In some cases, the actuator may move from about 10 mm to about 20 mm. In some cases, the actuator may move from about 20 mm to about 30 mm. In some cases, the actuator may move from about 30 mm to about 40 mm. In some cases, the actuator may move from about 40 mm to about 50 mm. In some cases, the actuator may move from about 27 mm to about 30 mm.
[0121] In some cases, the actuator may displace fluid. In some cases, the fluid displaced may be about 0.1 milliliters (mL) to about 100 mL. In some cases, the fluid displaced may be about 0.1 mL to about 0.25 mL. In some cases, the fluid displaced may be about 0.25 mL to about 0.5 mL. In some cases, the fluid displaced may be about 0.5 mL to about 0.75 mL. In some cases, the fluid displaced may be about 0.75 mL to about 1 mL. In some cases, the fluid displaced may be about 1 mL to about 25 mL. In some cases, the fluid displaced may be about 25 mL to about 50 mL. In some cases, the fluid displaced may be about 50 mL to about 75 mL. In some cases, the fluid displaced may be about 75 mL to about 100 mL. In some cases, the fluid displaced may be around 0.27 mL. In some cases, the fluid displaced may be around 3 mL.
[0122] In some cases, the actuator may produce a force. In some cases, the actuator force may be from about 10 Newton (N) to about 1000 N. In some cases, the actuator force may be from about 10 N to about 25 N. In some cases, the actuator force may be from about 25 N to about 50 N. In some cases, the actuator force may be from about 50 N to about 75 N. In some cases, the actuator force may be from about 75 N to about 100 N. In some cases, the actuator force may be from about 100 N to about 250 N. In some cases, the actuator force may be from about 250 N to about 500 N. In some cases, the actuator force may be from about 500 N to about 750 N. In some cases, the actuator force may be from about 750 N to about 1000 N. In some cases, the actuator force may be about 40 N.
[0123] In some cases, the oscillator may comprise an internal mechanism. In some cases, the internal mechanism may be a scaffolding mechanism. In some cases, the scaffolding mechanism may comprise a syringe. In some cases, the scaffolding mechanism may comprise a plurality of syringes. In some cases, the scaffolding mechanism may comprise at least one syringe. In some cases, the scaffolding mechanism may comprise at least two syringes. In some cases, the scaffolding mechanism may comprise two syringes. In some cases, the scaffolding mechanism may comprise at least three syringes. In some cases, the scaffolding mechanism may comprise three syringes. In some cases, the scaffolding mechanism may comprise at least four syringes. Insome cases, the scaffolding mechanism may comprise four syringes. In some cases, the scaffolding mechanism may comprise five syringes. In some cases, the scaffolding mechanism may comprise ten syringes. In some cases, the scaffolding mechanism may comprise at least ten syringes. In some cases, the scaffolding mechanism may comprise twenty syringes. In some examples, the plurality of syringes may comprise a non-metal material. In some examples, the plurality of syringes may comprise a polymer. In some examples, the plurality of syringes may comprise plastic. In some examples, the plurality of syringes may comprise polyurethane. In some cases, the plurality of syringes may comprise any GMP-acceptable material. In some examples, the plurality of syringes may comprise a seal. In some examples, the seal may comprise rubber. In some examples, the seal may comprise plastic.
[0124] In some cases, the plurality of syringes may contain a fluid. In some cases, the plurality of syringes may comprise a stabilizing agent. In some cases, the plurality of syringes may contain a reagent. In some cases, the plurality of syringes may contain a plurality of reagents. In some cases, the plurality of syringes may contain a precipitant solution. In some cases, the plurality of syringes may contain a substance solution. In some cases, the plurality of syringes may contain a motive fluid.
[0125] In some cases, the actuator may be configured to affect the internal mechanism. In some cases, the actuator may push and / or pull the internal mechanism. In some cases, the actuator may roughly push and / or pull the internal mechanism. In some cases, the actuator may precisely push and / or pull the internal mechanism. In some cases, the actuator may precisely push and / or pull the plurality of syringes of the internal mechanism. In some cases, the actuator may induce, or generate, a controlled motion within the system. In some cases, the actuator may generate a controlled motion of the fluids within the system.
[0126] In some cases, the oscillator may be constructed from a structural material. In some cases, the structural material can comprise any suitable material. In some cases, the structural material can comprise a metal, a metalloid, a nonmetal, derivatives thereof, or combinations thereof. In some cases, the structural material may be a metal. In some cases, the structural material may be an alloy. In some cases, the structural material may comprise any suitable metal, including, but not limited to, Ag, Al, Au, Bi, C, Cr, Cu, Fe, Mg, Mn, Ni, Pb, Sb, Sn, and Zn. In some cases, the structural material may be steel. In some cases, the structural material may be aluminum. In some cases, the structural material may be machined aluminum. In some cases, the structural material may be plastic. In some cases, the structural material may be polycarbonate. In some cases, the structural material may be polyimide. In some cases, the structural material may be polyether etherketone (PEEK). In some cases, the structural material may be Teflon (PTFE). In some cases, the structural material may be polyethylene. In some cases, the structural material may bethermoplastic. In some cases, the structural material may be acetal. In some cases, the structural material may be an epoxy resin. In some cases, the structural material may be polypropylene. In some cases, the structural material may be a fiber metal laminate. In some cases, the structural material may be a polymer matrix composite. In some cases, the structural material may be a ceramic matrix composite. In some cases, the structural material may be a metal matrix composite. In some cases, the structural material may be carbon fiber. In some cases, the structural material may be silicon carbide. In some cases, the structural material may be fiberglass. In some cases, the structural material may be coated. In some cases, the coating may be a protective coating. In some cases, the coating may be anodized protective coating. In some cases, the coating may be configured to reduced corrosion.
[0127] In some cases, the oscillator may have a length. In some cases, the oscillator length may be from about 10 mm to about 1000 mm. In some cases, the length may be from about 10 mm to about 250 mm. In some cases, the length may be from about 250 mm to about 500 mm. In some cases, the length may be from about 500 mm to about 750 mm. In some cases, the length may be from about 750 mm to about 1000 mm. In some cases, the length may be from about 50 mm to about 150 mm. In some cases, the length may be from about 150 mm to about 250 mm. In some cases, the oscillator length may be about 189 mm. In some cases, the oscillator length may be about 184.62 mm.
[0128] In some cases, the oscillator may have a width. In some cases, the oscillator width may be from about 10 mm to about 1000 mm. In some cases, the width may be from about 10 mm to about 250 mm. In some cases, the width may be from about 250 mm to about 500 mm. In some cases, the width may be from about 500 mm to about 750 mm. In some cases, the width may be from about 750 mm to about 1000 mm. In some cases, the width may be from about 50 mm to about 150 mm. In some cases, the oscillator width may be about 59 mm. In some cases, the oscillator width may be about 68.49 mm.
[0129] In some cases, the oscillator may have a height. In some cases, the oscillator height may be from about 10 mm to about 1000 mm. In some cases, the height may be from about 10 mm to about 250 mm. In some cases, the height may be from about 250 mm to about 500 mm. In some cases, the height may be from about 500 mm to about 750 mm. In some cases, the height may be from about 750 mm to about 1000 mm. In some cases, the height may be from about 50 mm to about 150 mm. In some cases, the oscillator height may be about 26 mm. In some cases, the oscillator height may be about 21.2 mm.
[0130] In some cases, the oscillator may have a mass. In some cases, the oscillator may have a dry mass, where the oscillator is not currently housing a reagent. In some cases, the oscillator dry mass may be from about 0.01 gram (g) to about 10000 g. In some cases, the oscillator dry massmay be from about 0.01 g to about 1 g. In some cases, the oscillator dry mass may be from about 1 g to about 2.5 g. In some cases, the oscillator dry mass may be from about 2.5 g to about 5 g. In some cases, the oscillator dry mass may be from about 5 g to about 50 g. In some cases, the oscillator dry mass may be from about 50 g to about 100 g. In some cases, the oscillator dry mass may be from about 100 g to about 500 g. In some cases, the oscillator dry mass may be from about 500 g to about 1000 g. In some cases, the oscillator dry mass may be from about 1000 g to about 10000 g. In some cases, the oscillator dry mass may be about 0.136 g.
[0131] In some cases, the oscillator may operate at a frequency. In some cases, the frequency may be from about 0.1 Hertz (Hz) to about 10 Hz. In some cases, the frequency may be from about 0.1 Hz to about 2.5 Hz. In some cases, the frequency may be from about 2.5 Hz to about 5 Hz. In some cases, the frequency may be from about 5 Hz to about 7.5 Hz. In some cases, the frequency may be from about 7.5 Hz to about 10 Hz. In some cases, the frequency may be from about 1 Hz to about 4 Hz.
[0132] In some cases, the oscillator consumes power for operation. In some cases, the oscillator may have a nominal power consumption. In some cases, the nominal power consumption may be from about 0.1 watts (W) to about 50 W. In some cases, the oscillator may have a peak power consumption. In some cases, the peak power consumption may be from about 0.1 watts (W) to about 200 W.
[0133] In some cases, the oscillator may be controlled. In some cases, the oscillator may be controlled by a system computer. In some cases, the oscillator may be controlled by an external computer. In some cases, the oscillator power may be controlled by pulse width modulation. In some cases, the oscillator power may be controlled by Transistor-Transistor Logic.
[0134] In some cases, the oscillator may operate under different conditions. In some cases, the oscillator may operate under a plurality of different condition sets. In some cases, the oscillator may operate under more than five sets of conditions. In some cases, the oscillator may operate under a first set of conditions. In some cases, the oscillator may operate under a second set of conditions. In some cases, the oscillator may operate under a third set of conditions. In some cases, the oscillator may operate under a more than three sets of conditions. In some cases, the oscillator may operate at a set of conditions, producing no fluid displacement.Reactor
[0135] FIGs. 10A-10U depict reactor (microreactor or X-plate) modules. A first reactor module is provided, where a plan view (first side) (FIG. 10A), plan view (top side) (FIG. 10B), plan view (top end) (FIG. 10C), plan view (second side) (FIG. 10D) and plan view (bottom side) (FIG.IOE) are provided. A second reactor module is provided, where a plan view (first side) (FIG.IOF), plan view (top side) (FIG. 10G), plan view (top end) (FIG. 10H), plan view (second side)(FIG. 101) and plan view (bottom side) (FIG. 10J) are provided. A third reactor module is provided, where a plan view (first side) (FIG. 10K), plan view (top side) (FIG. 10L), plan view (top end) (FIG. 10M), plan view (second side) (FIG. ION) and plan view (bottom side) (FIG. 100) are provided. A fourth reactor module is provided, where a plan view (first side) (FIG. 10P), plan view (top side) (FIG. 10Q), plan view (top end) (FIG. 10R), plan view (second side) (FIG. 10S) and plan view (bottom side) (FIG. 10T) are provided.
[0136] In some cases, the reactor may be configured to be a level of containment of the enclosed fluids.
[0137] In some cases, the reactor module may comprise a plurality of reactors. In some cases, the reactor module may comprise one reactor. In some cases, the reactor module may comprise at least one reactor. In some cases, the reactor module may comprise at least two reactors. In some cases, the reactor module may comprise two reactors. In some cases, the plurality of reactors may be connected. In some cases, the plurality of reactors may operate in parallel. In some cases, the plurality of reactors may be positioned laterally to one another. In some cases, the plurality of reactors may be stacked, with one reactor on top of another reactor. In some cases, the plurality of reactors may be stacked in multiple layers. In some cases, the interface between the plurality of reactors may be sealed. In some cases, the interface between the plurality of reactors may be sealed by an O-ring. In some cases, the interface between the plurality of reactors may be sealed by the reactors themselves, where the top of one reactor creates a seal with the bottom of another, as shown in FIG. 10U.
[0138] In some cases, the reactor may comprise a channel. In some cases, the reactor may comprise one channel. In some cases, the reactor may comprise at least one channel. In some cases, the reactor may comprise a plurality of channels. In some cases, the reactor may comprise a plurality of overlapping channels. In some cases, the reactor may comprise a plurality of intersecting channels. In some cases, the reactor may comprise one extended channel. In some cases, the reactor may comprise one extended channel, where the channel turns throughout the reactor. In some cases, the channel may be configured to allow for fluid to pass through the reactor. In some cases, the channel may be configured to allow for a plurality of reagents to pass through the reactor. In some cases, the channel may be configured to allow for a plurality of reagents to mix within the reactor. In some cases, the channel may be configured to allow for crystal growth. In some cases, the channel may be configured to minimize turbulence.
[0139] In some cases, the channel may have a cross-sectional distance. In some cases, the cross- sectional distance may be from about 1 mm to about 200 mm. In some cases, the cross-sectional distance may be from about 1 mm to about 5 mm. In some cases, the cross-sectional distance may be from about 5 mm to about 10 mm. In some cases, the cross-sectional distance may be fromabout 10 mm to about 50 mm. In some cases, the cross-sectional distance may be from about 50 mm to about 100 mm. In some cases, the cross-sectional distance may be from about 100 mm to about 150 mm. In some cases, the cross-sectional distance may be from about 150 mm to about 200 mm. In some cases, the cross-sectional distance may be 5 mm.
[0140] In some cases, the reactor may comprise a node. In some cases, the reactor may comprise a plurality of nodes. In some cases, the plurality of nodes may be positioned along the plurality of channels. In some cases, the plurality of nodes may be positioned along the one channel. In some cases, the plurality of nodes may be positioned within the channel. In some cases, the plurality of nodes may be periodically positioned along the channel. In some cases, the plurality of nodes may be non-periodically positioned along the channel. In some cases, the nodes may be throttling nodes, wherein the nodes are configured to support mixing of a plurality of reagents. In some cases, the nodes may have a geometry, wherein the node geometry may be configured to support mixing of a plurality of reagents.
[0141] In some cases, the nodes may have a length, wherein the length is the distance between two pinch points. In some cases, the node length may be from about 1 mm to about 300 mm. In some cases, the node length may be from about 1 mm to about 10 mm. In some cases, the node length may be from about 10 mm to about 20 mm. In some cases, the node length may be from about 20 mm to about 30 mm. In some cases, the node length may be from about 30 mm to about 40 mm. In some cases, the node length may be from about 40 mm to about 50 mm. In some cases, the node length may be from about 50 mm to about 100 mm. In some cases, the node length may be from about 100 mm to about 200 mm. In some cases, the node length may be from about 200 mm to about 300 mm. In some cases, the node length may be about 15 mm. In some cases, the nodes may have a width. In some cases, the width may be from about 1 mm to about 10 mm. In some cases, the width may be from about 1 mm to about 5 mm. In some cases, the width may be from about 5 mm to about 10 mm. In some cases, the width may be about 1 mm.
[0142] In some cases, the channel may comprise nodes. In some cases, the channel may be flat, wherein 0% of the channel comprises nodes. In some cases, the channel may comprise nodes, wherein the nodes comprise from 0 % to 100 % of the channel. In some cases, the nodes may comprise from about 0% to about 25% of the channel. In some cases, the nodes may comprise from about 25% to about 50% of the channel. In some cases, the nodes may comprise from about 50% to about 75% of the channel. In some cases, the nodes may comprise from about 75% to about 100% of the channel. In some cases, the nodes may comprise about 33% of the channel. In some cases, the nodes may cover one region of the channel. In some cases, the nodes may be dispersed across a plurality of regions of the channel.
[0143] In some cases, the channel may comprise at least one portion. In some cases, the portion may be flat, wherein no nodes are present. In some cases, the portion may comprise at least one node. In some cases, the channel may comprise one portion, wherein the portion may be a flat portion or a node portion. In some cases, the channel may comprise two portions. In some cases, the two portions may be a two flat portions, one flat portion / one node portion, or two node portions. In some cases, the channel may comprise three portions, where the three portions may be three flat portions, two flat / one nodes portions, one flat / two node portions, or three node portions. In some cases, the channel may comprise four portions, where the four portions may be four flat portions, three flat / one node portions, two flat / two node portions, one flat / three node portions, or four node portions. In some cases, the channel may comprise a plurality of portions. In some cases, the plurality of portions may comprise a combination of flat portions and node portions. In some cases, the plurality of portions may comprise all flat portions. In some cases, the plurality of portions may comprise all node portions. In some cases, the plurality of portions may be configured to process the plurality of reagents. In some cases, the plurality of portions may be configured to allow for contact of the plurality of reagents.
[0144] In some cases, the nodes may allow for reagent mixing. In some cases, the nodes may be configured to optimize reagent mixing. In some cases, the nodes may be configured to allow for turbulent mixing. In some cases, the nodes may be configured to allow for diffusive mixing. In some cases, the nodes may be configured to allow for convective mixing.
[0145] In some cases, the reactor may comprise a reactor material. In some cases, the reactor material may comprise a metal. In some cases, the reactor material may comprise a non-metal. In some cases, the reactor may comprise plastic. In some cases, the reactor may comprise biocompatible plastic. In some cases, the reactor material may be polycarbonate. In some cases, the reactor material may be polyimide. In some cases, the reactor material may be polyether etherketone (PEEK). In some cases, the reactor material may be Teflon (PTFE). In some cases, the reactor material may be polyethylene. In some cases, the reactor material may be thermoplastic. In some cases, the reactor material may be acetal. In some cases, the reactor material may be an epoxy resin. In some cases, the reactor material may be polypropylene. In some cases, the reactor material may be a fiber metal laminate. In some cases, the reactor material may be a polymer matrix composite. In some cases, the reactor material may be a ceramic matrix composite. In some cases, the reactor material may be a metal matrix composite. In some cases, the reactor material may be carbon fiber. In some cases, the reactor material may be silicon carbide. In some cases, the reactor material may be fiberglass. In some cases, the reactor may comprise material selected due to its weight. In some cases, the reactor may further comprise a seal. In some cases, the reactor may further comprise a plurality of seals. In some cases, the sealsare Viton® seals. In some cases, the reactor may further comprise bolts and fittings. In some cases, the bolts and fittings may be stainless steel.
[0146] In some cases, the reactor may be in fluid communication with further components of the system. In some cases, the reactor may be in fluid communication with the FSU. In some cases, the reactor may be in fluid communication with the oscillator. In some cases, the fluid communication may be established through a fluidic connection. In some cases, the fluidic connection may be established through permanent fittings. In some cases, the fluidic connection may be established through push fittings. In some cases, the fluidic connections may be Luer fittings. In some cases, the fluidic connection may be tubing. In some cases, the fluidic connection may have a diameter of from about 1 mm to about 50 mm. In some cases, the fluidic connection may have a diameter of from about 1 mm to about 5 mm. In some cases, the fluidic connection may have a diameter of from about 5 mm to about 10 mm. In some cases, the fluidic connection may have a diameter of from about 10 mm to about 25 mm. In some cases, the fluidic connection may have a diameter of from about 25 mm to about 50 mm. In some cases, the fluidic connection may have a diameter about 4 mm. In some cases, the fluidic connection may be selected due to their ease of used. In some cases, the fluidic connection may be selected due to their system compatibility. In some cases, the fluidic connection may be selected due to its leak-tightness. In some cases, the fluidic connection may be selected due to its vibrational durability.
[0147] In some cases, the reactor may have a mass. In some cases, the reactor may have a dry mass, where the reactor is not currently housing a reagent. In some cases, the reactor dry mass may be from about 0.1 kg to about 50 kg. In some cases, the dry mass may be from about 0.1 kg to about 1 kg. In some cases, the dry mass may be from about 1 kg to about 2 kg. In some cases, the dry mass may be from about 2 kg to about 3 kg. In some cases, the dry mass may be from about 3 kg to about 4 kg. In some cases, the dry mass may be from about 4 kg to about 5 kg. In some cases, the dry mass may be from about 5 kg to about 10 kg. In some cases, the dry mass may be from about 10 kg to about 25 kg. In some cases, the dry mass may be from about 25 kg to about 50 kg. In some cases, the dry mass may be from about 0.3 kg to about 0.8 kg. In some cases, the dry mass may be about 1.128 kg. In some cases, the reactor may have a wet mass, where the reactor is housing a reagent. In some cases, the reactor wet mass may be from about 0.1 kg to about 100 kg. In some cases, the wet mass may be from about 0.1 kg to about 1 kg. In some cases, the wet mass may be from about 1 kg to about 2 kg. In some cases, the wet mass may be from about 2 kg to about 3 kg. In some cases, the wet mass may be from about 3 kg to about 4 kg. In some cases, the wet mass may be from about 4 kg to about 5 kg. In some cases, the wet mass may be from about 5 kg to about 10 kg. In some cases, the wet mass may be from about 10 kg to about 50 kg. In some cases, the wet mass may be from about 50 kg to about 100 kg. In some cases, thewet mass may be from about 0.3 kg to about 0.8 kg. In some cases, the wet mass may be about 1.188 kg.
[0148] In some cases, the reactor may have a length. In some cases, the reactor length may be from about 10 mm to about 1000 mm. In some cases, the length may be from about 10 mm to about 250 mm. In some cases, the length may be from about 250 mm to about 500 mm. In some cases, the length may be from about 500 mm to about 750 mm. In some cases, the length may be from about 750 mm to about 1000 mm. In some cases, the length may be from about 50 mm to about 150 mm. In some cases, the length may be from about 150 mm to about 250 mm. In some cases, the reactor length may be about 244 mm. In some cases, the reactor length may be about 230 mm.
[0149] In some cases, the reactor may have a width. In some cases, the reactor width may be from about 10 mm to about 1000 mm. In some cases, the width may be from about 10 mm to about 250 mm. In some cases, the width may be from about 250 mm to about 500 mm. In some cases, the width may be from about 500 mm to about 750 mm. In some cases, the width may be from about 750 mm to about 1000 mm. In some cases, the width may be from about 50 mm to about 150 mm. In some cases, the reactor width may be about 95 mm.
[0150] In some cases, the reactor may have a height. In some cases, the reactor height may be from about 10 mm to about 1000 mm. In some cases, the height may be from about 10 mm to about 250 mm. In some cases, the height may be from about 250 mm to about 500 mm. In some cases, the height may be from about 500 mm to about 750 mm. In some cases, the height may be from about 750 mm to about 1000 mm. In some cases, the height may be from about 50 mm to about 150 mm. In some cases, the reactor height may be about 14 mm. In some cases, the reactor height may be about 50 mm.
[0151] In some cases, the reactor may comprise a plurality of bolts. In some cases, the bolts may have a diameter. In some cases, the diameter may be from about 1 mm to about 10 mm. In some cases, the diameter may be from about 1 mm to about 5 mm. In some cases, the diameter may be from about 5 mm to about 10 mm. In some cases, the diameter may be about 5.2 mm. In some cases, the plurality of bolts may be spaced apart. In some cases, the plurality of bolts may be from about 20 mm to about 60 mm apart. In some cases, the plurality of bolts may be from about 20 mm to about 40 mm apart. In some cases, the plurality of bolts may be from about 40 mm to about 60 mm apart. In some cases, the plurality of bolts may be about 27.3 mm apart. In some cases, the plurality of bolts may be about 27.15 mm apart. In some cases, the plurality of bolts may be about 55.54 mm apart.Pump Module
[0152] In some embodiments, the pump module may be a first pump. In some embodiments, the first pump may be configured to generate a constant flow rate of the plurality of reagents. In some embodiments, the first pump may be configured to generate a variable flow rate of the plurality of reagents. In some embodiments, the pump module may be a second pump. In some embodiments, the second pump may be configured to generate a constant flow rate of the plurality of reagents. In some embodiments, the second pump may be configured to generate a variable flow rate of the plurality of reagents. In some embodiments, the second pump may be the first pump.
[0153] In some cases, the system may comprise a pump module. FIGs. 11A-11F depict a pump module, where a left side (FIG. 11A), right side (FIG. 11B), top side (FIG. 11C), bottom side (FIG. 11D), overhead view (FIG. HE), and perspective view (FIG. HF) are provided. In some cases, the system may comprise a pump. In some cases, the pump module may comprise a sensor. In some cases, the pump module may comprise internal traps. In some cases, the pump module may comprise a valve. In some cases, the pump module may comprise a microcontroller. In some cases, the pump module components may be in fluid connection with one another. In some cases, the pump module components may be in electrical connection with one another. In some cases, the pump module is configured to maintain the experimental integrity. In some cases, the pump module may be configured to prevent fluid management issues. In some cases, the pump module may be configured to prevent contamination. In some cases, the pump module may be configured to be a level of containment of the enclosed fluids.
[0154] In some cases, the pump module may comprise a pump. In some cases, the pump module may comprise a plurality of pumps. In some cases, the pump may be a micro pump, such as a Bartels® MP7 micro pump. In some cases, the pump module may comprise a plurality of micro pumps. In some cases, the pump may be a fluid pump. In some cases, the pump may be an air pump. In some cases, the pump module may comprise one pump. In some cases, the pump module may comprise a plurality of pumps. In some cases, the pump module may comprise at least two pumps. In some cases, the pump module may comprise at least three pumps. In some cases, the pump module may comprise at least four pumps. In some cases, the pump module may comprise at least five pumps. In some cases, the pump module may comprise at least six pumps. In some cases, the pump module may comprise at least ten pumps. In some cases, the pump module may comprise a combination of pump types. In some cases, the pump module may comprise a combination of air pumps and fluid pumps. In some cases, the pump module may comprise four fluid pumps and one air pump.
[0155] In some cases, the pump module may comprise a sensor. In some cases, the pump module may comprise a plurality of sensors. In some cases, the pump module may comprise a flow sensor,such as an SLF35-0600F flow sensor. In some cases, the pump module may comprise a plurality of flow sensors.
[0156] In some cases, the pump module may comprise an internal trap. In some cases, the pump module may comprise a plurality of internal traps. In some cases, the pump module may comprise a bubble trap, such as a Bartels® mp-bt Bubble Trap. In some cases, the pump module may comprise a plurality of bubble traps. In some cases, the bubble traps may be configured to prevent air from reaching the reactor. In some cases, the bubble traps may be configured to ensure consistent fluid flow into the reactor. In some cases, the bubble traps may be configured to ensure bubble-free flow throughout the system.
[0157] In some cases, the pump module may comprise a valve, such as a Memetis® Single Valve, as shown in FIG. 15. In some cases, the pump module may comprise a plurality of valves. In some cases, the pump module may comprise a check valve, such as an Airlogic® F 2804403 valve. In some cases, the pump module may comprise a plurality of valves. In some cases, the valves are configured to prevent fluid backflow. In some cases, the valves are configured to prevent fluid backflow from the oscillator. In some cases, the valves are configured to ensure forward fluid movement.
[0158] In some cases, the pump module may comprise a controller unit. In some cases, the pump module may comprise an internal CPU. In some cases, the pump module may comprise a microcontroller, such as an ESP32 microcontroller. In some cases, the microcontroller may be configured to operate the pumps and micro pumps. In some cases, the microcontroller may be configured to operate the flow sensors. In some cases, the microcontroller may be configured to operate the valves. In some cases, the microcontroller may be configured to coordinate between the components of the pump module.
[0159] In some cases, the pump module may comprise a pump module material. In some cases, the pump module material may comprise a metal. In some cases, the pump module material may comprise a non-metal. In some cases, the pump module may comprise plastic. In some cases, the pump module may comprise polymer. In some cases, the pump module may comprise Acrylonitrile butadiene styrene (ABS). In some cases, the pump module may comprise polycarbonate. In some cases, the pump module may comprise resin. In some cases, the pump module may comprise UV resin fluid. In some cases, the pump module may further comprise bolts and fittings. In some cases, the bolts and fittings may be stainless steel. In some cases, the pump module may comprise electronics.
[0160] In some cases, the pump module may be configured to manage the fluid within the system. In some cases, the pump module may be configured to push the fluid through the system. In some cases, the pump module may be configured to push fluid from the FSU. In some cases, the pumpmodule may be configured to push fluid through the oscillator. In some cases, the pump module may be configured to push fluid through the reactor. In some cases, the pump module may be configured to push fluid through an observation module. In some cases, the pump module may be configured to push fluid to an outlet. In some cases, the pump module may be configured to push fluid to an output storage.
[0161] In some cases, the pump module may be configured to pump fluid at a flow rate. In some cases, the flow rate may be constant. In some cases, the flow rate may be variable. In some cases, the flow rate may be from about 0.1 milliliter / minute (mL / min) to about 15 mL / min. In some cases, the flow rate may be from about 0.1 mL / min to about 3 mL / min. In some cases, the flow rate may be from about 3 mL / min to about 6 mL / min. In some cases, the flow rate may be from about 6 mL / min to about 9 mL / min. In some cases, the flow rate may be from about 9 mL / min to about 12 mL / min. In some cases, the flow rate may be from about 12 mL / min to about 15 mL / min. In some cases, the flow rate may be from about 0.5 mL / min to about 3 mL / min.
[0162] In some cases, the pump module may be configured to pump at a pressure. In some cases, the pump module pressure may be from about 0.1 millibar (mbar) to about 500 mbar. In some cases, the pump module pressure may be from about 0.1 mbar to about 100 mbar. In some cases, the pump module pressure may be from about 100 mbar to about 200 mbar. In some cases, the pump module pressure may be from about 200 mbar to about 300 mbar. In some cases, the pump module pressure may be from about 300 mbar to about 400 mbar. In some cases, the pump module pressure may be from about 400 mbar to about 500 mbar.
[0163] In some cases, the pump module may have a nominal power consumption. In some cases, the nominal power consumption may be from about 0.1 watts (W) to about 50 W. In some cases, the nominal power consumption may be from about 0.1 W to about 1 W. In some cases, the nominal power consumption may be from about 1 W to about 10 W. In some cases, the nominal power consumption may be from about 10 W to about 20 W. In some cases, the nominal power consumption may be from about 20 W to about 30 W. In some cases, the nominal power consumption may be from about 30 W to about 40 W. In some cases, the nominal power consumption may be from about 40 W to about 50 W. In some cases, the nominal power consumption may be about 1.2 W.
[0164] In some cases, the pump module may have a peak power consumption. In some cases, the peak power consumption may be from about 0.1 W to about 200 W. In some cases, the peak power consumption may be from about 0.1 W to about 1 W. In some cases, the peak power consumption may be from about 1 W to about 20 W. In some cases, the peak power consumption may be from about 20 W to about 40 W. In some cases, the peak power consumption may be from about 40 W to about 60 W. In some cases, the peak power consumption may be from about 60 W to about 80W. In some cases, the peak power consumption may be from about 80 W to about 100 W. In some cases, the peak power consumption may be from about 100 W to about 150 W. In some cases, the peak power consumption may be from about 150 W to about 200 W. In some cases, the peak power consumption may be about 6 W. In some cases, the peak power consumption may be less than about 6 W.
[0165] In some cases, the pump module may have a mass. In some cases, the pump module may have a dry mass, where the pump module is not currently housing a reagent. In some cases, the pump module dry mass may be from about 1 g to about 50 kg. In some cases, the pump module dry mass may be from about 1 g to about 250 g. In some cases, the pump module dry mass may be from about 250 g to about 500 g. In some cases, the pump module dry mass may be from about 500 g to about 1 kg. In some cases, the pump module dry mass may be from about 1 kg to about 25 kg. In some cases, the pump module dry mass may be from about 25 kg to about 50 kg. In some cases, the pump module dry mass may be about 328 g.
[0166] In some cases, the pump module may have a length. In some cases, the pump module length may be from about 10 mm to about 1000 mm. In some cases, the length may be from about 10 mm to about 250 mm. In some cases, the length may be from about 250 mm to about 500 mm. In some cases, the length may be from about 500 mm to about 750 mm. In some cases, the length may be from about 750 mm to about 1000 mm. In some cases, the length may be from about 50 mm to about 150 mm. In some cases, the length may be from about 150 mm to about 250 mm. In some cases, the pump module length may be about 105 mm. In some cases, the pump module length may be about 119.3 mm.
[0167] In some cases, the pump module may have a width. In some cases, the pump module width may be from about 10 mm to about 1000 mm. In some cases, the width may be from about 10 mm to about 250 mm. In some cases, the width may be from about 250 mm to about 500 mm. In some cases, the width may be from about 500 mm to about 750 mm. In some cases, the width may be from about 750 mm to about 1000 mm. In some cases, the width may be from about 50 mm to about 150 mm. In some cases, the pump module width may be about 95 mm. In some cases, the pump module width may be about 98 mm.
[0168] In some cases, the pump module may have a height. In some cases, the pump module height may be from about 10 mm to about 1000 mm. In some cases, the height may be from about 10 mm to about 250 mm. In some cases, the height may be from about 250 mm to about 500 mm. In some cases, the height may be from about 500 mm to about 750 mm. In some cases, the height may be from about 750 mm to about 1000 mm. In some cases, the height may be from about 50 mm to about 150 mm. In some cases, the pump module height may be about 22 mm. In some cases, the pump module height may be about 27 mm.Observation Module
[0169] In some embodiments, the system may comprise an observation module configured to detect a signal associated with the set of crystallization characteristics using an optical instrument. In some embodiments, the crystallized substance may flow from the reactor to the observation module. In some embodiments, an optical sensor may be configured to detect the signal when the oscillator is in a condition other than the first set of conditions.
[0170] In some cases, the system may comprise an observation module. FIGs. 12A-12E depict an observation module, where a plan view (underside) view (FIG. 12A), overhead view (FIG. 12B), side view (FIG. 12C), front side view (FIG. 12D), and perspective view (FIG. 12E) are provided. In some cases, the observation module may be configured to monitor crystallization within the system. In some cases, the observation module may be configured to monitor crystallization after mixing of the plurality of reagents. In some cases, the observation module may be configured to analyze crystal size. In some cases, the observation module may be configured to analyze crystal morphology. In some cases, the observation module may be constructed from specialized components. In some cases, the observation module may be constructed from off the shelf components. In some cases, the observation module may be configured to capture crystal images. In some cases, the observation module may be configured to capture high-resolution crystal images. In some cases, the observation module may be configured to record data. In some cases, the observation module may be configured to be a component of a feedback system, wherein the observation module data may be used to control other modules of the system.
[0171] In some cases, the observation module may comprise an imaging device. In some cases, the observation module may comprise a microscope. In some cases, the observation module may comprise a camera. In some cases, the observation module may comprise an optical instrument.
[0172] In some cases, the observation module may comprise an imaging device, such as a camera. In some cases, the camera may be a Raspberry Pi HQ camera. In some cases, the camera may be 12.3MP Sony® IMX477. In some cases, the imaging device may be configured to be compatible with a computer. In some cases, the imaging device may be selected due to its resolution capability. In some cases, the imaging device may be configured to capture crystals. In some cases, the crystals may be 15 microns or greater.
[0173] In some cases, the imaging device may be a microscope. In some cases, the microscope may be a white light back-lit system. In some cases, the microscope may comprise a light diffuser. In some cases, the microscope may comprise a 2-part lens. In some cases, the lens may have a coating, such as a TAG-BAR coating. In some cases, the lens may have a coating configured to minimize chromatic aberration.
[0174] In some cases, the imaging device may comprise a CCD sensor. In some cases, the imaging device may comprise an a-chromatic lens. In some cases, the lens may have a diameter. In some cases, the diameter may be from about 1 mm to about 20 mm. In some cases, the diameter may be from about 1 mm to about 10 mm. In some cases, the diameter may be from about 10 mm to about 20 mm. In some cases, the diameter may be about 9 mm. In some cases, the lens may be configured to provide optical magnification. In some cases, the imaging device may comprise a backlight setup. In some cases, the backlight setup may comprise a light source. In some cases, the backlight setup may comprise an array of LEDs. In some cases, the backlight setup may comprise a light diffusing component.
[0175] In some cases, the observation module may capture images at a resolution. In some cases, the resolution may be from 0.5 microns / pixel to 20 microns / pixel. In some cases, the resolution may be from 0.5 microns / pixel to 2.5 microns / pixel. In some cases, the resolution may be from 2.5 microns / pixel to 5 microns / pixel. In some cases, the resolution may be from 5 microns / pixel to 10 microns / pixel. In some cases, the resolution may be from 10 microns / pixel to 20 microns / pixel. In some cases, the resolution may be from 1 microns / pixel to 1.5 microns / pixel. In some cases, the resolution may be selected to identify individual crystals. In some cases, the resolution may be selected to identify individual crystal sizes. In some cases, the resolution may be selected to view crystals of at least 10 microns in diameter.
[0176] In some cases, the observation module may be in fluid communication with the reactor. In some cases, the observation module may comprise a channel, wherein the channel is configured to allow for fluid flow. In some cases, the observation module may comprise a channel, wherein the channel is configured to allow for crystal observation. In some cases, the observation module may comprise a channel. In some cases, the observation module may comprise a plurality of channels. In some cases, the observation module may comprise one channel. In some cases, the observation module may comprise more than one channel. In some cases, the observation module may comprise two channels. In some cases, the observation module may comprise three channels. In some cases, the observation module may comprise four channels. In some cases, the observation module may comprise a number of channels equal to imaging devices. In some cases, the observation module may comprise a number of channels equal to the number of reactors within the reactor.
[0177] In some cases, the observation module may comprise a channel. In some cases, the channel may be shallow. In some cases, the channel may have a depth from about 100 microns to about 600 microns. In some cases, the channel may have a depth from about 100 microns to about 350 microns. In some cases, the channel may have a depth from about 350 microns to about 600microns. In some cases, the channel may have a depth of around 400 microns. In some cases, the depth may be configured to prevent crystal overlap when imaged.
[0178] In some cases, the observation module may comprise a microprocessor. In some cases, the observation module may comprise a printed circuit board. In some cases, the observation module may comprise a computing unit, such as a Raspberry Pi. In some cases, the Raspberry Pi may be connected to an imaging device. In some cases, more than one imaging device may be connected.In some cases, one imaging device may be connected. In some cases, two imaging devices may be connected. In some cases, three imaging devices may be connected. In some cases, four imaging devices may be connected.
[0179] In some cases, the observation module may comprise an observation module material. In some cases, the observation module material may comprise a metal. In some cases, the observation module material may be an alloy. In some cases, the observation module material may comprise zinc-aluminum alloy. In some cases, the observation module material may comprise any suitable metal, including, but not limited to, Ag, Al, Au, Bi, C, Cr, Cu, Fe, Mg, Mn, Ni, Pb, Sb, Sn, and Zn. In some cases, the observation module material may be steel. In some cases, the observation module material may be aluminum. In some cases, the observation module material may comprise stainless steel. In some cases, the observation module material may comprise a non-metal. In some cases, the observation module may comprise plastic. In some cases, the observation module may comprise polymer. In some cases, the observation module may comprise Acrylonitrile butadiene styrene (ABS). In some cases, the observation module may comprise TOPAS® COC polymer.
[0180] In some cases, the observation module may have a nominal power consumption. In some cases, the nominal power consumption may be from about 0.1 watts (W) to about 50 W. In some cases, the nominal power consumption may be from about 0.1 W to about 1 W. In some cases, the nominal power consumption may be from about 1 W to about 10 W. In some cases, the nominal power consumption may be from about 10 W to about 20 W. In some cases, the nominal power consumption may be from about 20 W to about 30 W. In some cases, the nominal power consumption may be from about 30 W to about 40 W. In some cases, the nominal power consumption may be from about 40 W to about 50 W. In some cases, the nominal power consumption may be about 0.4 W.
[0181] In some cases, the observation module may have a peak power consumption. In some cases, the peak power consumption may be from about 0.1 W to about 200 W. In some cases, the peak power consumption may be from about 0.1 W to about 1 W. In some cases, the peak power consumption may be from about 1 W to about 20 W. In some cases, the peak power consumption may be from about 20 W to about 40 W. In some cases, the peak power consumption may be from about 40 W to about 60 W. In some cases, the peak power consumption may be from about 60 Wto about 80 W. In some cases, the peak power consumption may be from about 80 W to about 100 W. In some cases, the peak power consumption may be from about 100 W to about 150 W. In some cases, the peak power consumption may be from about 150 W to about 200 W. In some cases, the peak power consumption may be about 1.6 W.
[0182] In some cases, the observation module may have a mass. In some cases, the observation module may have a dry mass per imaging device, where the observation module is not currently housing a reagent. In some cases, the observation module dry mass may be from about 1 g to about 20 kg per imaging device. In some cases, the observation module dry mass may be from about 1 g to about 250 g per imaging device. In some cases, the observation module dry mass may be from about 250 g to about 500 g per imaging device. In some cases, the observation module dry mass may be from about 500 g to about 1 kg per imaging device. In some cases, the observation module dry mass may be from about 1 kg to about 10 kg per imaging device. In some cases, the observation module dry mass may be from about 10 kg to about 20 kg per imaging device. In some cases, the observation module dry mass may be about 150 g per imaging device. In some cases, the observation module dry mass may be less than about 150 g per imaging device.
[0183] In some cases, the observation module may have a length. In some cases, the observation module length may be from about 10 mm to about 1000 mm. In some cases, the length may be from about 10 mm to about 250 mm. In some cases, the length may be from about 250 mm to about 500 mm. In some cases, the length may be from about 500 mm to about 750 mm. In some cases, the length may be from about 750 mm to about 1000 mm. In some cases, the length may be from about 50 mm to about 150 mm. In some cases, the length may be from about 150 mm to about 250 mm. In some cases, the observation module length may be about 70 mm. In some cases, the observation module length may be about 117 mm.
[0184] In some cases, the observation module may have a width. In some cases, the observation module width may be from about 10 mm to about 1000 mm. In some cases, the width may be from about 10 mm to about 250 mm. In some cases, the width may be from about 250 mm to about 500 mm. In some cases, the width may be from about 500 mm to about 750 mm. In some cases, the width may be from about 750 mm to about 1000 mm. In some cases, the width may be from about 50 mm to about 150 mm. In some cases, the observation module width may be about 40 mm. In some cases, the observation module width may be about 56 mm.
[0185] In some cases, the observation module may have a height. In some cases, the observation module height may be from about 10 mm to about 1000 mm. In some cases, the height may be from about 10 mm to about 250 mm. In some cases, the height may be from about 250 mm to about 500 mm. In some cases, the height may be from about 500 mm to about 750 mm. In some cases, the height may be from about 750 mm to about 1000 mm. In some cases, the height may befrom about 50 mm to about 150 mm. In some cases, the observation module height may be about 38 mm. In some cases, the observation module height may be about 84.16 mm.Power System
[0186] In some cases, the system may comprise a power system. In some cases, the power system may be connected through lines. In some cases, the system may be connected through harnesses. In some cases, the system may be connected through connectors. In some cases, the system may comprise a payload controller (PC).
[0187] FIGs. 13A-13E depict a payload controller, where a side view (FIG. 13A), left side view (FIG. 13B), right side view (FIG. 13C), plan view (underside) (FIG. 13D), and perspective view (FIG. 13E) are provided.
[0188] In some embodiments, the PC may comprise a computing module, such as a Raspberry Pi. In some cases, the PC may be configured to command the system operations. In some cases, the PC may be configured to control the system operations. In some cases, the PC may be configured to manage the system operations. In some cases, the PC may be configured to process data collected by the observation module. In some cases, the PC may be configured to analyze data in real time. In some cases, the PC may be configured to store observation module images and data. In some cases, the PC may operate based on a simplified software system, as shown in FIG. 21.
[0189] In some cases, the PC may be configured to interface with the PMU. In some cases, the PC may be configured to interface with each component of the PMU. In some cases, the PC may be configured to interface with each component of the PMU independently. In some cases, the PC may be configured to interface with any component that the CCU may interface with. In some cases, the PC may be configured to interface with any component that the CCU may interface with, wherein the CCU may be redundant to the PC. In some cases, the PC may be configured to interface with any component that the CCU may interface with, wherein the CCU may be a component of the PC.
[0190] In some cases, the PC may be configured to interface with the observation module. In some cases, the PC may be configured to interface with the imaging device of the observation module. In some cases, the PC may be configured to interface with two imaging devices. In some cases, the PC may be configured to interface with a plurality of imaging devices. In some cases, the PC may be configured to execute pre-programmed commands. In some cases, the PC may be configured to adjust system parameters.
[0191] In some cases, the PC may comprise a graphics processing unit (GPU). In some cases, the PC may comprise a processor. In some cases, the processor may be a high-performance processor. In some cases, the processor may be, for example, a 2.4GHz quad-core 64-bit Arm Cortex-A76 CPU. In some cases, the PC may comprise a GPU. In some cases, the GPU may be, for example,a VideoCore® IV GPU. In some cases, the PC may comprise a built-in clock. In some cases, thePC may be connected to an external clock. In some cases, the PC may comprise a memory unit. In some cases, the PC may have 8 GB RAM. In some cases, the PC may be in connection to a central controlling unit.
[0192] In some cases, the PC may have a nominal power consumption. In some cases, the nominal power consumption may be from about 0.1 watts (W) to about 50 W. In some cases, the nominal power consumption may be from about 0.1 W to about 1 W. In some cases, the nominal power consumption may be from about 1 W to about 10 W. In some cases, the nominal power consumption may be from about 10 W to about 20 W. In some cases, the nominal power consumption may be from about 20 W to about 30 W. In some cases, the nominal power consumption may be from about 30 W to about 40 W. In some cases, the nominal power consumption may be from about 40 W to about 50 W. In some cases, the nominal power consumption may 1 >e about 1.3 W.
[0193] In some cases, the PC may have a peak power consumption. In some cases, the peak power consumption may be from about 0.1 W to about 200 W. In some cases, the peak power consumption may be from about 0.1 W to about 1 W. In some cases, the peak power consumption may be from about 1 W to about 20 W. In some cases, the peak power consumption may be from about 20 W to about 40 W. In some cases, the peak power consumption may be from about 40 W to about 60 W. In some cases, the peak power consumption may be from about 60 W to about 80 W. In some cases, the peak power consumption may be from about 80 W to about 100 W. In some cases, the peak power consumption may be from about 100 W to about 150 W. In some cases, the peak power consumption may be from about 150 W to about 200 W. In some cases, the peak power consumption may be about 6 W.
[0194] In some cases, the PC may have a mass. In some cases, the PC mass may be from about 1 g to about 500 g. In some cases, the PC mass may be from about 1 g to about 250 g. In some cases, the PC mass may be from about 250 g to about 500 g. In some cases, the PC mass may be about44 g.
[0195] In some cases, the PC may have a length. In some cases, the PC length may be from about 10 mm to about 1000 mm. In some cases, the length may be from about 10 mm to about 250 mm. In some cases, the length may be from about 250 mm to about 500 mm. In some cases, the length may be from about 500 mm to about 750 mm. In some cases, the length may be from about 750 mm to about 1000 mm. In some cases, the length may be from about 50 mm to about 150 mm. In some cases, the length may be from about 150 mm to about 250 mm. In some cases, the PC length may be about 85 mm. In some cases, the PC length may be about 88.3 mm.
[0196] In some cases, the PC may have a width. In some cases, the PC width may be from about 10 mm to about 1000 mm. In some cases, the width may be from about 10 mm to about 250 mm. In some cases, the width may be from about 250 mm to about 500 mm. In some cases, the width may be from about 500 mm to about 750 mm. In some cases, the width may be from about 750 mm to about 1000 mm. In some cases, the width may be from about 50 mm to about 150 mm. In some cases, the PC width may be about 56 mm. In some cases, the PC width may be about 78.45 mm.
[0197] In some cases, the PC may have a height. In some cases, the PC height may be from about 10 mm to about 1000 mm. In some cases, the height may be from about 10 mm to about 250 mm. In some cases, the height may be from about 250 mm to about 500 mm. In some cases, the height may be from about 500 mm to about 750 mm. In some cases, the height may be from about 750 mm to about 1000 mm. In some cases, the height may be from about 50 mm to about 150 mm. In some cases, the PC height may be about 24.97 mm.
[0198] In some cases, the system may comprise a central controlling unit (CCU), as shown in FIG. 14. In some cases, the CCU may be configured to manage specific subsystems of the system. In some cases, the CCU may be configured to manage the pump module. In some cases, the CCU may be configured to manage the oscillator. In some cases, the CCU may be configured to manage internal sensors. In some cases, the CCU may further comprise a microcontroller, such as an Arduino® Nano. In some cases, the CCU may further comprise an interface, such as an RS485HD interface. In some cases, the CCU may comprise a processing unit, wherein the processing unit is integrated. In some cases, the CCU may comprise a processing unit, wherein the processing unit is auxiliary. In some cases, the CCU may be configured for power monitoring. In some cases, the CCU may be configured for latch-up event protection.
[0199] In some cases, the CCU may have a power consumption. In some cases, the power consumption may be from about 0.1 W to about 200 W. In some cases, the power consumption may be from about 0.1 W to about 1 W. In some cases, the power consumption may be from about 1 W to about 20 W. In some cases, the power consumption may be from about 20 W to about 40 W. In some cases, the power consumption may be from about 40 W to about 60 W. In some cases, the power consumption may be from about 60 W to about 80 W. In some cases, the power consumption may be from about 80 W to about 100 W. In some cases, the power consumption may be from about 100 W to about 150 W. In some cases, the power consumption may be from about 150 W to about 200 W. In some cases, the power consumption may be about 1.2 W.
[0200] In some cases, the CCU may have a mass. In some cases, the CCU mass may be from about 1 g to about 500 g. In some cases, the CCU mass may be from about 1 g to about 250 g. Insome cases, the CCU mass may be from about 250 g to about 500 g. In some cases, the CCU mass may be about 51 g.
[0201] In some cases, the CCU may have a length. In some cases, the CCU length may be from about 10 mm to about 1000 mm. In some cases, the length may be from about 10 mm to about 250 mm. In some cases, the length may be from about 250 mm to about 500 mm. In some cases, the length may be from about 500 mm to about 750 mm. In some cases, the length may be from about 750 mm to about 1000 mm. In some cases, the length may be from about 50 mm to about 150 mm. In some cases, the length may be from about 150 mm to about 250 mm. In some cases, the CCU length may be about 119 mm.
[0202] In some cases, the CCU may have a width. In some cases, the CCU width may be from about 10 mm to about 1000 mm. In some cases, the width may be from about 10 mm to about 250 mm. In some cases, the width may be from about 250 mm to about 500 mm. In some cases, the width may be from about 500 mm to about 750 mm. In some cases, the width may be from about 750 mm to about 1000 mm. In some cases, the width may be from about 50 mm to about 150 mm. In some cases, the CCU width may be about 86 mm.
[0203] In some cases, the CCU may have a height. In some cases, the CCU height may be from about 10 mm to about 1000 mm. In some cases, the height may be from about 10 mm to about 250 mm. In some cases, the height may be from about 250 mm to about 500 mm. In some cases, the height may be from about 500 mm to about 750 mm. In some cases, the height may be from about 750 mm to about 1000 mm. In some cases, the height may be from about 50 mm to about 150 mm. In some cases, the CCU height may be about 6 mm.
[0204] In some cases, the system may further comprise a power distribution unit (PDU). In some cases, the PDU may be configured to manage the electrical power distribution within the system. In some cases, the PDU may be configured to handle power lines. In some cases, the PDU may be configured to handle any suitable power lines, such as 3.3V, 5V, 6V, 9V, 12V, 24V, 120V, 208V, 240V, 21T or 480V, for example. In some cases, the PDU may be configured to handle 5V power lines. In some cases, the PDU may be configured to handle 12V power lines. In some cases, the PDU may comprise circuits. In some cases, the PDU may comprise protection circuits. In some cases, the PDU may be configured to protect the system from power surges. In some cases, the PDU may be configured to protect the system from voltage irregularities. In some cases, the PDU may be configured to protect the system from potential faults. In some cases, the PDU may be adherent to industry standards, such as ECSS-E-ST-20-20C for power systems in space environments. In some cases, the PDU may be configured for EMI filtering.
[0205] In some cases, the PDU may have a power consumption. In some cases, the power consumption may be from about 0.1 W to about 200 W. In some cases, the power consumptionmay be from about 0.1 W to about 1 W. In some cases, the power consumption may be from about 1 W to about 20 W. In some cases, the power consumption may be from about 20 W to about 40 W. In some cases, the power consumption may be from about 40 W to about 60 W. In some cases, the power consumption may be from about 60 W to about 80 W. In some cases, the power consumption may be from about 80 W to about 100 W. In some cases, the power consumption may be from about 100 W to about 150 W. In some cases, the power consumption may be from about 150 W to about 200 W. In some cases, the power consumption may be about 1.2 W.
[0206] In some cases, the PDU may have a mass. In some cases, the PDU mass may be from about 1 g to about 500 g. In some cases, the PDU mass may be from about 1 g to about 250 g. In some cases, the PDU mass may be from about 250 g to about 500 g. In some cases, the PDU mass may be about 51 g.
[0207] In some cases, the PDU may have a length. In some cases, the PDU length may be from about 10 mm to about 1000 mm. In some cases, the length may be from about 10 mm to about 250 mm. In some cases, the length may be from about 250 mm to about 500 mm. In some cases, the length may be from about 500 mm to about 750 mm. In some cases, the length may be from about 750 mm to about 1000 mm. In some cases, the length may be from about 50 mm to about 150 mm. In some cases, the length may be from about 150 mm to about 250 mm. In some cases, the PDU length may be about 119 mm.
[0208] In some cases, the PDU may have a width. In some cases, the PDU width may be from about 10 mm to about 1000 mm. In some cases, the width may be from about 10 mm to about 250 mm. In some cases, the width may be from about 250 mm to about 500 mm. In some cases, the width may be from about 500 mm to about 750 mm. In some cases, the width may be from about 750 mm to about 1000 mm. In some cases, the width may be from about 50 mm to about 150 mm. In some cases, the PDU width may be about 86 mm.
[0209] In some cases, the PDU may have a height. In some cases, the PDU height may be from about 10 mm to about 1000 mm. In some cases, the height may be from about 10 mm to about 250 mm. In some cases, the height may be from about 250 mm to about 500 mm. In some cases, the height may be from about 500 mm to about 750 mm. In some cases, the height may be from about 750 mm to about 1000 mm. In some cases, the height may be from about 50 mm to about 150 mm. In some cases, the PDU height may be about 6 mm.
[0210] In some cases, the system may comprise a power data interface (PDI). In some cases, the PDI may be configured for data transmission. In some cases, the PDI may be in physical connected to the system or the system components / modules. In some cases, the physical connection may be via a power line. In some cases, the physical connection may be via a data line. In some cases, the PDI may be in signal connection to the system or system components / modules. In some cases, thesignal connection may be over Wi-Fi. In some cases, the connection may be selected based on risk of failed connections. In some cases, the PDI may be selected to ensure reliable communication. In some cases, the PDI may be selected to ensure reliable power delivery.
[0211] In some cases, the PDI may maintain levels of containment. In some cases, the level of containment may be through an internal PCB mounted to a frame. In some cases, the PDI may maintain a level of containment by an interconnecting header. In some cases, the header may be sealed by an O-ring. In some cases, the header may be sealed by a double O-ring formation, as shown in FIG. 17. Further, the PDI exterior to the O-ring is shown in FIG. 18A and the PDI interior to the O-ring is shown in FIG. 18B. In some cases, the PDI may be sealed by a cover. In some cases, the PDI may be sealed by a chemical-resistant cover, such as an Ultem 9085 cover.
[0212] In some cases, the PDI may have a mass. In some cases, the PDI mass may be from about 1 g to about 500 g. In some cases, the PDI mass may be from about 1 g to about 250 g. In some cases, the PDI mass may be from about 250 g to about 500 g. In some cases, the PDI mass may be about 50 g.
[0213] In some cases, the PDI may have a length. In some cases, the PDI length may be from about 10 mm to about 1000 mm. In some cases, the length may be from about 10 mm to about 250 mm. In some cases, the length may be from about 250 mm to about 500 mm. In some cases, the length may be from about 500 mm to about 750 mm. In some cases, the length may be from about 750 mm to about 1000 mm. In some cases, the length may be from about 50 mm to about 150 mm. In some cases, the length may be from about 150 mm to about 250 mm. In some cases, the PDI length may be about 100 mm.
[0214] In some cases, the PDI may have a width. In some cases, the PDI width may be from about 10 mm to about 1000 mm. In some cases, the width may be from about 10 mm to about 250 mm. In some cases, the width may be from about 250 mm to about 500 mm. In some cases, the width may be from about 500 mm to about 750 mm. In some cases, the width may be from about 750 mm to about 1000 mm. In some cases, the width may be from about 50 mm to about 150 mm. In some cases, the PDI width may be about 100 mm.
[0215] In some cases, the PDI may have a height. In some cases, the PDI height may be from about 10 mm to about 1000 mm. In some cases, the height may be from about 10 mm to about 250 mm. In some cases, the height may be from about 250 mm to about 500 mm. In some cases, the height may be from about 500 mm to about 750 mm. In some cases, the height may be from about 750 mm to about 1000 mm. In some cases, the height may be from about 50 mm to about 150 mm. In some cases, the PDI height may be about 50 mm.
[0216] In some cases, the system may further comprise valves, where a valve is shown in FIG. 15. In some cases, the system may comprise a plurality of valves. In some cases, the system maycomprise one valve. In some cases, the system may comprise more than one valve. In some cases, the system may comprise a plurality of valves essential for system operation.
[0217] In some cases, the valves may be configured to maintain system fluid integrity. In some cases, the valves may be configured to prevent unwanted fluid flow. In some cases, the valves may be configured to prevent premature fluid flow into the output. In some cases, the valves may be configured to allow for batch fluid change. In some cases, the valves may be configured to create a separation barrier between fluid components. In some cases, the valves may prevent excessive mixing. In some cases, the valves may prevent interaction between stored fluid, input fluid, and / or fluid within the reactor. In some cases, the valves are configured for process containment. In some cases, the valves are configured for fluid management.
[0218] In some cases, the valves are controlled, wherein the valves may be opened or closed. In some cases, the valves are current-controlled. In some cases, the valves may be detector controlled. In some cases, the valves may be configured to remain closed unless prompted otherwise. In some cases, the valves may be configured to remain closed to minimize fluid drain. In some cases, the valves may be configured to remain closed when not in operation, where the valves open during operation.
[0219] In some cases, the valves may comprise structural material. In some cases, the structural material may comprise metal. In some cases, the structural material comprise non-metal. In some cases, the structural material may comprise a polymer. In some cases, the structural material may comprise plastic. In some cases, the structural material may comprise PEEK. In some cases, the structural material may comprise silicon. In some cases, the structural material may comprise polyethylene.
[0220] In some cases, the valves may comprise a fluid manifold. In some cases, the valves may comprise a membrane. In some cases, the valves may comprise fittings, such as Luer fittings. In some cases, the valves may be single direction valves. In some cases, the valves may be two-way valves. In some cases, the valves may be media separated valves. In some cases, the valves may be sterilized. In some cases, the valves may be sterilized by autoclaving.
[0221] In some cases, the valves may have a pressure. In some cases, the pressure may be from about 0 bar to about 5 bar. In some cases, the pressure may be from about 0 bar to about 2.5 bar. In some cases, the pressure may be from about 2.5 bar to about 5 bar. In some cases, the pressure may be from about 0 bar to about 3 bar.
[0222] In some cases, the each of the valves may have a mass. In some cases, the valves mass may be from about 1 g to about 500 g. In some cases, the valves mass may be from about 1 g to about 250 g. In some cases, the valves mass may be from about 250 g to about 500 g. In some cases, the valves mass may be about 10 g.
[0223] In some cases, the each of the valves may have a length. In some cases, the valves length may be from about 10 mm to about 1000 mm. In some cases, the length may be from about 10 mm to about 250 mm. In some cases, the length may be from about 250 mm to about 500 mm. In some cases, the length may be from about 500 mm to about 750 mm. In some cases, the length may be from about 750 mm to about 1000 mm. In some cases, the length may be from about 50 mm to about 150 mm. In some cases, the length may be from about 150 mm to about 250 mm. In some cases, the valves length may be about 100 mm.
[0224] In some cases, the each of the valves may have a width. In some cases, the valves width may be from about 10 mm to about 1000 mm. In some cases, the width may be from about 10 mm to about 250 mm. In some cases, the width may be from about 250 mm to about 500 mm. In some cases, the width may be from about 500 mm to about 750 mm. In some cases, the width may be from about 750 mm to about 1000 mm. In some cases, the width may be from about 50 mm to about 150 mm. In some cases, the valves width may be about 100 mm.
[0225] In some cases, the each of the valves may have a height. In some cases, the valves height may be from about 10 mm to about 1000 mm. In some cases, the height may be from about 10 mm to about 250 mm. In some cases, the height may be from about 250 mm to about 500 mm. In some cases, the height may be from about 500 mm to about 750 mm. In some cases, the height may be from about 750 mm to about 1000 mm. In some cases, the height may be from about 50 mm to about 150 mm. In some cases, the valves height may be about 50 mm.
[0226] In some cases, the system may comprise internal monitors. In some cases, the internal monitors may be temperature loggers, such as MAXIM iButton® DS1922L temperature loggers, as shown in FIG. 19. In some cases, a plurality of monitors may be present. In some cases, the temperature loggers may be configured to be environmentally stable, and rugged. In some cases, the temperature loggers may be configured to store temperature data in an internal memory. In some cases, the temperature loggers may be selected due to their durability for ISS work.
[0227] In some cases, the system may comprise a plurality of temperature loggers. In some cases, the temperature loggers may be positioned throughout the system. In some cases, the plurality of temperature loggers may be configured to map temperatures throughout the system. In some cases, the plurality of temperature loggers may be configured to produce a thermal map. In some cases, the plurality of temperature loggers may be positioned throughout the system based on the systems thermal environment. In some cases, the thermal environment may depend on external environment. In some cases, the thermal environment may be from around -50 °C to about 100 °C. In some cases, the thermal environment may be from around 18 °C to about 30 °C.
[0228] In some cases, the each of the temperature loggers may have a mass. In some cases, the temperature logger mass may be from about 1 g to about 50 g. In some cases, the temperaturelogger mass may be from about 1 g to about 25 g. In some cases, the temperature logger mass may be from about 250 g to about 50 g. In some cases, the temperature logger mass may be about 6 g.
[0229] In some embodiments, the system may further comprise a storage container configured to hold the crystallized substance.
[0230] In some cases, the system may further comprise a fluid output. In some cases, the fluid output may be a separate module. In some cases, the fluid output may be a component of the FSU. In some cases, the fluid output may be an internal container. In some cases, the fluid output may be an external container. In some cases, the crystallization system may be configured to direct the final product into the fluid output. In some cases, the fluid output may be configured to store the produced crystals. In some cases, the fluid output may comprise an output bag. In some cases, the fluid output may comprise a plurality of output bags. In some cases, the fluid output may comprise one output bag. In some cases, the fluid output may comprise two output bags. In some cases, the fluid output may comprise three output bags. In some cases, the fluid output may comprise three or more output bags.
[0231] In some cases, the system may comprise further fluid transfer components to allow for proper fluid management, wherein the fluid transfer components relationship with the modules / components can be seen in FIG. 2. In some cases, the fluid transfer components are configured to handle and process the internal fluids. In some cases, the internal fluid may be a substance solution. In some cases, the internal fluid is a precipitant solution. In some cases, the internal fluid may be a combination of substance solution and precipitant solution. In some cases, the internal fluid may be a combination of solution and formed crystals. In some cases, the fluid transfer components may be configured to transfer fluid from the FSU to the reactors and ultimately to the output fluid storage. In some cases, the fluid transfer components may be configured to transfer fluid between modules of the system.
[0232] In some cases, the fluid transfer components may comprise tubing. In some cases, the tubing may be configured to transfer fluid between modules / components. In some cases, the tubing material may be selected depending on compatibility with the fluid transferred. In some cases, the tubing material may be selected depending on chemical compatibility. In some cases, the tubing material may be selected based on its chemical resistance. In some cases, the tubing material may be selected based on its permeability, wherein the permeability may be minimal. In some cases, the tubing material may be selected based on its mechanical stability. In some cases, the tubing material may be selected based on operational pressure and temperature.
[0233] In some cases, the fluid transfer components may comprise pumps. In some cases, the pumps may be positioned throughout the system. In some cases, the pumps may be positioned along the tubes. In some cases, the pumps may be configured to draw fluid into the system. Insome cases, the pumps may be configured to mix fluids throughout the system. In some cases, the pumps may be configured to maintain flow rates within the system. In some cases, the pumps may be controlled by a dedicated PCB.
[0234] In some cases, the fluid transfer components may comprise bubble traps. In some cases, the fluid transfer components may be configured to capture air bubbles within the system. In some cases, the fluid transfer components may be configured to capture air bubbles within the tubing. In some cases, the fluid transfer components may be configured to eliminate air bubbles within the system. In some cases, the fluid transfer components may be configured to eliminate air bubbles within the tubing. In some cases, the bubble traps may be configured for operation in microgravity.
[0235] In some cases, the fluid transfer components may comprise valves, as disclosed herein. In some cases, the fluid transfer components may comprise fittings.
[0236] In some cases, the system may comprise a feedback loop. In some cases, the feedback loop may connect one module of the system to another module. In some cases, the system may be configured to use a feedback loop to iteratively adjust the first set of conditions responsive to detecting a signal associated with the set of crystallization characteristics. In some cases, the system may be configured to use a feedback loop to iteratively adjust the second set of conditions responsive to detecting a signal associated with the set of crystallization characteristics.
[0237] In some cases, the system may be positioned on a vehicle. In some cases, the system may be positioned on a launch vehicle. In some cases, the system may be positioned within a payload. In some cases, the system may be the payload. In some cases, the system may be positioned on a spacecraft. In some cases, the system may be positioned on a manned spacecraft. In some cases, the system may be positioned on an unmanned spacecraft. In some cases, the system may be positioned on a rocket. In some cases, the system may be positioned on a satellite. In some cases, the system may be positioned on the International Space Station (ISS).
[0238] In an aspect, disclosed herein is a kit for use in a microgravity environment. In some embodiments, the kit may comprise a first reagent and second reagent. In some embodiments, the first reagent may be a precipitant solution, as disclosed herein. In some embodiments, the precipitant solution may comprise zinc chloride, sodium citrate tribasic dihydrate, acetone, or a combination thereof. In some embodiments, the second reagent may be a substance solution, as disclosed herein. In some embodiment, the substance solution may comprise a solution of a noncrystallized form or a crystal seed form of the substance. In some embodiments, the noncrystallized form of the substance may comprise insulin. In some embodiments, a launch vehicle may comprise the kit. In some cases, a payload may comprise the kit. In some cases, the payload may be the kit. In some cases, a spacecraft may comprise the kit. In some cases, anorbiting vehicle (such as a satellite or ISS) may comprise the kit. In some cases, a rocket may comprise the kit. In some embodiments, the launch vehicle may comprise a rocket and a payload comprising the kit.
[0239] In an aspect, disclosed herein is a kit for synthesizing a drug a microgravity environment. In some cases, the kit may be configured to crystallize a substance in microgravity. In some embodiments, the kit may comprise a first reagent and second reagent. In some embodiments, the first reagent may be a precipitant solution, as disclosed herein. In some embodiments, the precipitant solution may comprise zinc chloride, sodium citrate tribasic dihydrate, acetone, or a combination thereof. In some embodiments, the second reagent may be a substance solution, as disclosed herein. In some embodiment, the substance solution may comprise a solution of a noncrystallized form or a crystal seed form of the substance. In some embodiments, the noncrystallized form of the substance may comprise insulin. In some embodiments, a launch vehicle may comprise the kit. In some cases, a payload may comprise the kit. In some cases, a spacecraft may comprise the kit. In some cases, an orbiting vehicle (such as a satellite or ISS) may comprise the kit. In some cases, a rocket may comprise the kit. In some embodiments, the launch vehicle may comprise a rocket and a payload comprising the kit.Methods for continuous crystallization in microgravity environments
[0240] In an aspect, disclosed herein is a method for crystallizing a substance in a microgravity environment. In some embodiments, the method may comprise receiving a plurality of reagents from at least one source into a reactor. In some embodiments, the reactor comprises at least one channel with at least a first portion and a second portion for processing the plurality of reagents. In some embodiments, the method may comprise contacting the plurality of reagents within the first portion. In some embodiments, the first portion comprises a plurality of periodic or nonperiodic throttling nodes for optimizing a type of mixing of the plurality of reagents. In some embodiments, the method may comprise displacing the plurality of reagents using a first set of conditions when the plurality of reagents is within the first portion. In some embodiments, the first set of conditions is sufficient to cause the type of mixing of a subset of the plurality of reagents. In some embodiments, the method may comprise contacting the subset of the plurality of reagents within the second portion. In some embodiments, the second portion comprises a uniform profile for optimizing crystallizing the subset of the plurality reagents using a second set of conditions sufficient to yield a crystallized substance having a set of crystallization characteristics.
[0241] In some cases, the method may be performed by the system / PMU, disclosed herein.
[0242] In some cases, the system may comprise reagents. In some cases, the reagents may be a plurality of reagents. In some cases, the reagents may be two reagents. In some cases, the reagentsmay be three reagents. In some cases, the reagents may be three or more reagents. In some cases, the reagent may be a first reagent. In some cases, the reagent may be a second reagent. In some cases, the reagent may be a precipitant solution. In some cases, the precipitant solution may comprise an organic solvent. In some cases, the precipitant solution may be an aqueous solution. In some cases, the precipitant solution may comprise a salt solution, such as KC1, NaCl, NaCCh, BaCh, CaCh, NaNCh, Na2SCh, Na2S2Ch, AgNCh, ZnBn, or ZnCh. In some cases, the precipitant solution may comprise a salt. In some cases, the precipitant solution may comprise water. In some cases, the precipitant solution may comprise sodium citrate tribasic. In some cases, the precipitant solution pay comprise acetone. In some cases, the precipitant solution may comprise any suitable components or a combination thereof. In some cases, the reagent may be a substance solution. In some cases, the substance solution may comprise an organic solvent. In some cases, the substance solution may be an aqueous solution. In some cases, the substance solution may comprise any suitable components. In some cases, the substance solution may comprise an acid. In some cases, the substance solution may comprise an acid, such as HC2H3O2, H3BO3, CH2O3, H3C6H5O7, HC1, HF, HNO3, H2C2O4, H3PO4 and H2SO4. In some cases, the substance solution may comprise water. In some cases, the substance solution may comprise a target substance. In some cases, the substance solution may comprise a target protein substance. In some cases, the substance solution may comprise a noncrystallized form of the target substance. In some cases, the substance may comprise a crystal seed form of the target solution.
[0243] In some cases, the system may comprise a source. In some cases, the system source may be a plurality of sources. In some cases, the system source may be at least one source. In some cases, the system source may be at least two sources.
[0244] In some cases, a geometry of the throttling nodes may be configured to support the type of mixing. In some cases, the reactor may comprise a node. In some cases, the reactor may comprise a plurality of nodes. In some cases, the plurality of nodes may be positioned along the plurality of channels. In some cases, the plurality of nodes may be positioned along the one channel. In some cases, the plurality of nodes may be positioned within the channel. In some cases, the plurality of nodes may be periodically positioned along the channel. In some cases, the plurality of nodes may be non-periodically positioned along the channel. In some cases, the nodes may be throttling nodes, wherein the nodes are configured to support mixing of a plurality of reagents. In some cases, the nodes may have a geometry, wherein the node geometry may be configured to support mixing of a plurality of reagents.
[0245] In some cases, the channel may comprise at least one portion. In some cases, the portion may be flat, wherein no nodes are present. In some cases, the portion may comprise at least one node. In some cases, the channel may comprise one portion, wherein the portion may be a flatportion or a node portion. In some cases, the channel may comprise two portions. In some cases, the two portions may be a two flat portions, one flat portion / one node portion, or two node portions. In some cases, the channel may comprise three portions, where the three portions may be three flat portions, two flat / one nodes portions, one flat / two node portions, or three node portions. In some cases, the channel may comprise four portions, where the four portions may be four flat portions, three flat / one node portions, two flat / two node portions, one flat / three node portions, or four node portions. In some cases, the channel may comprise a plurality of portions. In some cases, the plurality of portions may comprise a combination of flat portions and node portions. In some cases, the plurality of portions may comprise all flat portions. In some cases, the plurality of portions may comprise all node portions.
[0246] In some embodiments, the method may comprise storing the plurality of reagents in at least one container. In some cases, the plurality of reagents may be stored in an FSU. In some cases, the plurality of reagents may be stored in at least one FSU, or internal container. In some cases, the FSU may comprise at least one internal container. In some cases, the FSU may be at least one source. In some cases, the FSU may be at least two sources. In some cases, the FSU may comprise an input. In some cases, the FSU may comprise an input bag. In some cases, the FSU may comprise a plurality of input bags. In some cases, the FSU may comprise at least one input bag. In some cases, the FSU may comprise at least two input bags. In some cases, the FSU may comprise at least three input bags. In some cases, the FSU may comprise a number of input bags equal to the number of reagents. In some cases, the FSU may comprise a case. In some cases, the FSU may comprise fasteners, such as screws and bolts.
[0247] In some embodiments, the method further comprises pumping the plurality of reagents from the at least one source to the reactor using a set of pumping conditions. In some cases, the pumping condition may be pressure. In some cases, the pumping condition may be fluid viscosity. In some cases, the pumping condition may be fluid agitation. In some cases, the pumping condition may be pump power. In some cases, the pumping condition may be flow rate. In some cases, the pumping condition may generate a constant flow rate of the plurality of reagents. In some cases, the pumping condition may generate a variable flow rate of the plurality of reagents. In some cases, the pump conditions may generate a constant displacement frequency. In some cases, the pump conditions may generate a nonconstant displacement frequency. In some cases, the pump conditions may generate a constant displacement amplitude of the plurality of reagents. In some cases, the pump conditions may generate a nonconstant displacement amplitude of the plurality of reagents.
[0248] In some cases, the pumping may be at a flow rate. In some cases, the flow rate may be constant. In some cases, the flow rate may be variable. In some cases, the flow rate may be fromabout 0.1 mL / min to about 15 mL / min. In some cases, the flow rate may be from about 0.1 mL / min to about 3 mL / min. In some cases, the flow rate may be from about 3 mL / min to about 6 mL / min. In some cases, the flow rate may be from about 6 mL / min to about 9 mL / min. In some cases, the flow rate may be from about 9 mL / min to about 12 mL / min. In some cases, the flow rate may be from about 12 mL / min to about 15 mL / min. In some cases, the flow rate may be from about 0.5 mL / min to about 3 mL / min.
[0249] In some cases, the pumping may be at a pressure. In some cases, the pumping pressure may be from about 0.1 mbar to about 500 mbar. In some cases, the pumping pressure may be from about 0.1 mbar to about 100 mbar. In some cases, the pumping pressure may be from about 100 mbar to about 200 mbar. In some cases, the pumping pressure may be from about 200 mbar to about 300 mbar. In some cases, the pumping pressure may be from about 300 mbar to about 400 mbar. In some cases, the pumping pressure may be from about 400 mbar to about 500 mbar.
[0250] In some cases, the type of mixing is a diffusive mixing of the plurality of reagents. In some cases, the type of mixing is a convective mixing of the plurality of reagents. In some cases, the type of mixing is a convective mixing and a diffusive mixing of the plurality of reagents. In some cases, the nodes may allow for reagent mixing. In some cases, the nodes may be configured to optimize reagent mixing. In some cases, the nodes may be configured to allow for turbulent mixing. In some cases, the nodes may be configured to allow for diffusive mixing. In some cases, the nodes may be configured to allow for convective mixing.
[0251] In some cases, the first set of conditions and the second set of conditions may accelerate mixing. In some cases, the first set of conditions and the second set of conditions may accelerate mixing of the plurality of reagents. In some cases, the first set of conditions and the second set of conditions may accelerate mixing of the plurality of reagents compared to a different set of conditions. The different set of conditions may be based on factors, such as temperature, humidity, pressure, vibrational characteristics, and gravity. In some cases, the conditions may be Earth conditions. In some cases, the conditions may be lunar conditions. In some cases, the conditions may be microgravity conditions. In some cases, the mixing may be accelerated by at least 1% compared to a different set of conditions. In some cases, the mixing may be accelerated by at least 3% compared to a different set of conditions. In some cases, the mixing may be accelerated by at least 5% compared to a different set of conditions. In some cases, the mixing may be accelerated by at least 10% compared to a different set of conditions. In some cases, the mixing may be accelerated by at least 15% compared to a different set of conditions. In some cases, the mixing may be accelerated by at least 20% compared to a different set of conditions.
[0252] In some cases, the first set of conditions and the second set of conditions may alter crystallization rate. In some cases, the first set of conditions and the second set of conditions mayaccelerate crystallization. In some cases, the first set of conditions and the second set of conditions may improve crystallization quality. In some cases, the first set of conditions and the second set of conditions may accelerate crystallization of the plurality of reagents. In some cases, the first set of conditions and the second set of conditions may accelerate crystallization of the plurality of reagents compared to a different set of conditions. The different set of conditions may be based on factors, such as temperature, humidity, pressure, vibrational characteristics, and gravity. In some cases, the conditions may be Earth conditions. In some cases, the conditions may be lunar conditions. In some cases, the conditions may be microgravity conditions. In some cases, the crystallization may be accelerated by at least 1% compared to a different set of conditions. In some cases, the crystallization may be accelerated by at least 3% compared to a different set of conditions. In some cases, the crystallization may be accelerated by at least 5% compared to a different set of conditions. In some cases, the crystallization may be accelerated by at least 10% compared to a different set of conditions. In some cases, the crystallization may be accelerated by at least 15% compared to a different set of conditions. In some cases, the crystallization may be accelerated by at least 20% compared to a different set of conditions.
[0253] In some cases, the first set of conditions and the second set of conditions may improve at least one crystallization characteristic, wherein the characteristic may be crystal size, shape, ordered structure, quality, or purity, among others. In some cases, the first set of conditions and the second set of conditions may improve at least one crystallization characteristic of the plurality of reagents. In some cases, the first set of conditions and the second set of conditions may improve at least one crystallization characteristic of the plurality of reagents compared to a different set of conditions. The different set of conditions may be based on factors, such as temperature, humidity, pressure, vibrational characteristics, and gravity. In some cases, the conditions may be Earth conditions. In some cases, the conditions may be lunar conditions. In some cases, the conditions may be microgravity conditions. In some cases, the improvement may be by at least 1% compared to a different set of conditions. In some cases, the improvement may be by at least 3% compared to a different set of conditions. In some cases, the improvement may be by at least 5% compared to a different set of conditions. In some cases, the improvement may be by at least 10% compared to a different set of conditions. In some cases, the improvement may be by at least 15% compared to a different set of conditions. In some cases, the improvement may be by at least 20% compared to a different set of conditions.
[0254] In some cases, the first set of conditions or the second set of conditions may improve at least one crystallization characteristic, wherein the characteristic may be crystal size, shape, ordered structure, or purity, among others. In some cases, the first set of conditions or the second set of conditions may improve at least one crystallization characteristic of the plurality of reagents.In some cases, the first set of conditions or the second set of conditions may improve at least one crystallization characteristic of the plurality of reagents compared to a different set of conditions. The different set of conditions may be based on factors, such as temperature, humidity, pressure, vibrational characteristics, and gravity. In some cases, the conditions may be Earth conditions. In some cases, the conditions may be lunar conditions. In some cases, the conditions may be microgravity conditions. In some cases, the improvement may be by at least 1% compared to a different set of conditions. In some cases, the improvement may be by at least 3% compared to a different set of conditions. In some cases, the improvement may be by at least 5% compared to a different set of conditions. In some cases, the improvement may be by at least 10% compared to a different set of conditions. In some cases, the improvement may be by at least 15% compared to a different set of conditions. In some cases, the improvement may be by at least 20% compared to a different set of conditions.
[0255] In some cases, the method may further comprise adjusting the conditions while the system is operable. In some cases, the adjustment may be of the first set of conditions. In some cases, the adjustment may be of the second set of conditions. In some cases, the adjustment may be of any set of conditions. In some cases, the adjustment may be responsive to signal detection. In some cases, the adjustment may be responsive to detection from the observation module. In some cases, the adjustment may be increasingly adjusted. In some cases, the adjustment may be adjusted iteratively. In some cases, the adjustment may be in response to the crystallization rate. In some cases, the adjustment may be in response to mixing rate. In some cases, the adjustment may be in response to at least one crystallization characteristic. In some embodiments, the method may further comprise iteratively adjusting the first set of conditions responsive to detecting a signal associated with the set of crystallization characteristics. In some embodiments, the method may further comprise iteratively adjusting the second set of conditions responsive to detecting a signal associated with the set of crystallization characteristics.
[0256] In some embodiments, the method may further comprise detecting a signal from (i) the mixing in the first portion, (ii) the crystallizing in the second portion, or both. In some cases, signal detection may be completed by sensors internal to the system. In some cases, signal detection may be completed by sensors external to the system. In some cases, signal detection may be a part of a feedback loop, wherein the signal detection is directed to another component of the system. In some embodiments, the signal detecting comprises using an optical instrument to detect the signal. In some embodiments, the signal may be processed to determine the crystallization characteristics.
[0257] In some cases, the signal detection may be completed by the observation module, as disclosed herein. In some cases, the observation module may comprise an imaging device. In some cases, the observation module may comprise a microscope. In some cases, the observation modulemay comprise a camera. In some cases, the observation module may comprise an optical instrument.
[0258] In some cases, the signal detection may be completed in a position within the system outside of the observation module. In some cases, the signal detection may be completed by an internal sensor. In some cases, the signal detection may be measured through electromagnetic waves. In some cases, the signal detection may be measured through UV waves. In some cases, the signal detection may be measured through infrared waves.
[0259] In some embodiments, the method may further comprise using one or more containers to store the crystallized substance or unreacted reagents. In some cases, the fluid output may be an internal container. In some cases, the fluid output may be an external container. In some cases, the fluid output may be a storage container configured to hold the crystallized product. In some cases, the crystallization system may be configured to direct the final product into the fluid output. In some cases, the fluid output may be configured to store the produced crystals. In some cases, the fluid output may comprise an output bag. In some cases, the fluid output may comprise a plurality of output bags. In some cases, the fluid output may comprise one output bag. In some cases, the fluid output may comprise two output bags. In some cases, the fluid output may comprise three output bags. In some cases, the fluid output may comprise three or more output bags.
[0260] In some cases, the method may be autonomously performed without input by a user. In some embodiments, the method may be autonomously performed using a controller. In some cases, the method may be autonomously performed using a microcontroller. In some cases, the method may be autonomously performed using a CPU. In some cases, the method may be performed with the input of a user. In some cases, the method may be performed by a local user. In some cases, the method may be performed by a remote user. In some cases, the method may be performed by a user operating a remote controller.
[0261] In some cases, the method may take place in a selected environment. In some cases, the method may take place in low earth orbit (LEO). In some cases, the method may take place in medium earth orbit (MEO). In some cases, the method may take place in geostationary orbit (GEO). In some cases, the method may take place on Earth. In some cases, the method may take place in lunar orbit. In some cases, the method may take place on terrestrial gravity. In some cases, the method may take place in microgravity. In some embodiments, the microgravity environment is in low earth orbit (LEO), medium earth orbit (MEO), or geostationary orbit (GEO).
[0262] In some cases, the microgravity environment may be in a position in orbit. In some cases, the microgravity environment may be in a position in orbit assigned to or controlled by a country. In some cases, the microgravity environment may be in a position in orbit assigned to or controlled by a jurisdiction. In some embodiments, the microgravity environment is in an orbit assigned toor controlled by a country or a jurisdiction, and wherein the country or the jurisdiction is the USA, Europe, Japan, China, the United Kingdom, Russia, or India. In some cases, the microgravity environment may be in a position in orbit assigned to or controlled by the United States. In some cases, the microgravity environment may be in a position in orbit assigned to or controlled by the United Kingdom. In some cases, the microgravity environment may be in a position in orbit assigned to or controlled by Europe. In some cases, the microgravity environment may be in a position in orbit assigned to or controlled by China. In some cases, the microgravity environment may be in a position in orbit assigned to or controlled by Japan. In some cases, the microgravity environment may be in a position in orbit assigned to or controlled by India. In some cases, the microgravity environment may be in a position in orbit assigned to or controlled by Russia. In some cases, the microgravity environment may be in a position in orbit assigned to or controlled by Russia. In some cases, the microgravity environment may be in a position in orbit assigned to or controlled by the African Union, Algeria, Argentina, Australia, Austria, Azerbaijan, Bangladesh, Belgium, Brazil, Bulgaria, Canada, Chile, Costa Rica, Czechia, Denmark, Egypt, El Salvador, Ethiopia, France, Germany, Ghana, Greece, Hungary, Indonesia, Iran, Israel, Italy, Kazakhstan, Kenya, South Korea, CELAC, Lithuania, Luxembourg, Malaysia, Mexico, Mongolia, Morocco, Netherlands, New Zealand, Nigeria, Norway, Pakistan, Paraguay, Peru, Philippines, Poland, Portugal, Romania, Rwanda, Saudi Arabia, Singapore, South Africa, Spain, Sweden, Switzerland, Syria, Taiwan, Thailand, Tunisia, Turkey, Turkmenistan, Ukraine, UAE, United Nations, Uzbekistan, Venezuela, or Vietnam. In some cases, the microgravity environment may be on the moon or in an orbit of the moon. In some cases, the microgravity environment may be in a position in orbit assigned to or controlled by any nation with space capability. In some cases, the microgravity environment may be in a position in orbit assigned to or controlled by any nation. In some cases, the microgravity environment may be in a position in orbit assigned to or controlled by another planet.
[0263] In some cases, the method may further comprise transporting of the crystallized substance. In some cases, the method may further comprise transporting of the unreacted reagents. In some cases, the method may further comprise transporting of the waste material. In some cases, the method may further comprise transporting of the crystallized substance from one environment to another. In some cases, the method may further comprise transporting of the crystallized substance from one gravitational environment to another gravitational environment. In some embodiments, the method may further comprise transporting the crystallized substance from the microgravity environment to a terrestrial environment or location.
[0264] In some cases, the method may further comprise manufacturing of a product. In some cases, the method may further comprise manufacturing of a pharmaceutical drug. In some cases,the method may further comprise manufacturing of an agricultural substance. In some cases, the method may further comprise manufacturing of a precursor material. In some cases, the method may further comprise manufacturing of a pre-approval compound. In some cases, the method may further comprise manufacturing of a product from the crystallized substance. In some cases, the method may further comprise manufacturing of a product from the crystallized substance in the microgravity environment. In some cases, the method may further comprise manufacturing of a product from the crystallized substance in the terrestrial environment. In some embodiments, the method may further comprise manufacturing a pharmaceutical drug from the crystallized substance in the microgravity environment or a terrestrial environment or location.
[0265] In some cases, the method may further comprise processing of the crystallized substance. In some cases, the method may further comprise processing of the crystallized substance in a microgravity environment. In some cases, the method may further comprise processing of the crystallized substance in a terrestrial environment. In some cases, the method may further comprise processing of the crystallized substance to yield a product. In some cases, the method may further comprise processing of the crystallized substance to yield a pharmaceutical drug. In some cases, the method may further comprise processing of the crystallized substance to yield a precursor material. In some cases, the method may further comprise processing of the crystallized substance to yield a pre-approved compound. In some cases, the method may further comprise processing of the crystallized substance to yield an agricultural substance. In some embodiments, the method may further comprise processing the crystallized substance in the microgravity environment to yield a pharmaceutical drug.
[0266] In some cases, the method may further comprise transporting of the product. In some cases, the method may further comprise transporting of the pharmaceutical drug. In some cases, the method may further comprise transporting of the pre-approved compound. In some cases, the method may further comprise transporting of the precursor material. In some cases, the method may further comprise transporting of the agricultural substance. In some cases, the method may further comprise transporting of the product from a microgravity environment. In some cases, the method may further comprise transporting of the product to a terrestrial environment. In some embodiments, the method may further comprise transporting the pharmaceutical drug from the microgravity environment to a terrestrial environment or location.
[0267] In an aspect, disclosed herein is a method for transporting a kit to a microgravity environment. In some embodiments, the method comprises securing the kit to a launch vehicle. In some embodiments, the method comprises launching the launch vehicle to the microgravity environment from a terrestrial environment. In some cases, the method comprises launching the launch vehicle to the microgravity environment. In some cases, the launch vehicle may be aspacecraft. In some cases, the launch vehicle may be a rocket. In some embodiments, the launch vehicle may comprise a rocket and a payload. In some embodiments, a payload comprising the kit. In some embodiments, the microgravity environment may be in low earth orbit (LEO), medium earth orbit (MEO), or geostationary Orbit (GEO). In some embodiments, the payload may be in an orbit assigned to or controlled by a country, and wherein the country is the USA, Europe, Japan, China, Russia, or India.
[0268] In an aspect, disclosed herein is a method for transporting a crystallized substance from a microgravity environment. In some embodiments, the method comprises securing the container comprising the crystallized substance to an entry vehicle. In some embodiments, the method comprises returning the entry vehicle from the microgravity environment to a terrestrial environment. In some cases, the method comprises returning the entry vehicle from the microgravity environment. In some cases, the entry vehicle may be a spacecraft. In some cases, the entry vehicle may comprise a rocket. In some embodiments, the entry vehicle may comprise a payload. In some embodiments, the payload may comprise the crystallized substance. In some embodiments, the payload may be in low earth orbit (LEO), medium earth orbit (MEO), or geostationary Orbit (GEO) prior to returning from the microgravity environment. In some embodiments, the payload may be in an orbit assigned to or controlled by a country, and wherein the country is the USA, Europe, Japan, China, Russia, or India prior to returning from the microgravity environment.Methods for training a machine learning model
[0269] In some cases, models herein (e.g., an optimization model for determining or predicting the first set of conditions or the second set of conditions) can include machine (ML) models. Many ML methods implemented as algorithms are suitable as approaches to perform the methods described herein. Such methods include but are not limited to supervised learning approaches, unsupervised learning approaches, semi-supervised approaches, or any combination thereof. In some cases, ML methods may allow for optimization of crystal formation and growth by determining or predicting the first set of conditions or the second set of conditions.
[0270] Machine learning algorithms may include without limitation neural networks (e.g., artificial neural networks (ANN), multi-layer perceptrons (MLP), long short-term memory (LSTM)), support vector machines, k-nearest neighbors, Gaussian mixture model, Gaussian process, naive Bayes, decision trees, random forest, or gradient boosting trees. Linear machine learning algorithms may include without limitation linear regression with or without regularizer, logistic regression, naive Bayes classifier, perceptron, or support vector machines (SVMs). Other machine learning algorithms for use with methods according to the present disclosure may include without limitation quadratic classifiers, k-nearest neighbor, boosting, decision trees, randomforests, neural networks, pattern recognition, Bayesian networks, or Hidden Markov models. Other machine learning algorithms, including improvements or combinations of any of these, commonly used for machine learning, can also be suitable for use with the methods described herein. Any use of a machine learning algorithm in a workflow can also be suitable for use with the methods described herein. The workflow can include, for example, cross-validation, nested- cross-validation, feature selection, row compression, data transformation, binning, normalization, standardization, and algorithm selection.
[0271] A machine learning algorithm can generally be trained by the following methodology to build a machine learning model. In some cases, generated models may predict conditions for optimizing crystal growth or formation, e.g., the first or second set of conditions. In some cases, the dimension of the nodes and distribution of the nodes may be considered. In some cases, input data may include fluid flow data, crystal formation data, crystal growth data, crystal sedimentation data, oscillator conditions data, power consumption data, or waste fluid data. Output data can include, for example, the optimized conditions for crystallization growth.
[0272] 1. Gather a dataset for “training” and “testing” the machine learning algorithm. The dataset can include many features, for example, features associated with the first or second set of conditions. The training dataset is used to “train” the machine learning algorithm. The testing dataset is used to “test” the machine learning algorithm.
[0273] 2. Determine “features” for the machine learning algorithm to use for training and testing. The accuracy of the machine learning algorithm may depend on how the features are represented. For example, feature values may be transformed using one-hot encoding, binning, standardization, or normalization. Also, not all features in the dataset may be used to train and test the machine learning algorithm. Selection of features may depend on, for example, available computing resources and time or importance of features discovered during iterative testing and training. For example, it may be discovered that features associated with the first set of conditions are predictive for optimizing crystal growth.
[0274] 3. Choose an appropriate machine learning algorithm. For example, a machine learning algorithm described elsewhere herein may be chosen. The chosen machine learning algorithm may depend on, for example, available computing resources and time or whether the prediction is continuous or categorical in nature. The machine learning algorithm is used to build the machine learning model.
[0275] 4. Build the machine learning model. The machine learning algorithm is run on the gathered training dataset. Parameters of the machine learning algorithm may be adjusted by optimizing performance on the training dataset or via cross-validation datasets. After parameter adjustment and learning, the performance of the machine learning algorithm may be validated ona dataset of naive samples that are separate from the training dataset and testing dataset. The built machine learning model can involve feature coefficients, importance measures, or weightings assigned to individual features.
[0276] Once the machine learning model is determined as described above (“trained”), it can be used to predict or determine optimal conditions for crystal growth.Examples
[0277] While various examples of the present disclosure have been shown and described herein, such examples are provided by way of example only. Numerous variations, changes, or substitutions may occur without departing from the present disclosure. It should be understood that various alternatives to the examples described herein may be employed.Example 1 — “Antibody Diamonds” missionBackground to the Experiment
[0278] By 2040, it is predicted that there will be 28 million new cases of cancer each year globally (See Cancer Research UK, Lifetime Risk of Cancer herein). Anticancer antibody drugs are given to patients intravenously which is a long and painful procedure, taking 4-7 hours every few weeks requiring a hospital environment. Crystallization of these drugs allows for formulations that can be administered directly under the skin, allowing patients to treat themselves at home, just as diabetics self-inject with insulin. This dramatically reduces the burden on the healthcare system whilst also increasing the patient’s quality of life.
[0279] Crystallization of antibodies on Earth has had limited success due to gravity-induced phenomena inhibiting crystal growth, resulting in a range of sizes with many imperfections that are un-suitable for clinical use (FIG. 26A). The benefit of microgravity for the crystallization of proteins has been demonstrated over the past few decades on the ISS (FIG. 26B). The recent crystallization success of the world’s best-selling antibody drug, Keytruda See Rei chart et al herein) demonstrated that production in microgravity produces crystals of a high enough quality for pharmaceutical use.
[0280] For the full impact and benefit of antibody crystallization to be realized for humankind - commercial scale production of protein crystals must be achieved. The infrastructure for re-entry and permanent facilities in space is well underway, but what is missing is the specialist hardware for large-scale crystallization. Described herein is a pharmaceuticals factory in space (or PMU) including hardware to scale-up the production of protein crystals. In some cases, the PMU can be deployed onboard commercial space stations such as Axiom. In some cases, the PMU can be tested and validated onboard commercial space stations. Describe herein is a methodology for deploying, testing, and validating a PMU onboard a commercial space stations.Experimental Methodology
[0281] The experiment can evaluate and validate the hardware for the continuous pro-duction of protein crystals in microgravity for use onboard a commercial space station. The two experimentation lines can include 1) the quality and yield of the crystals obtained and 2) the user interface between astronauts and the instrument for reagent replenishment of the hardware. The crystallization reaction can be monitored in real time through in-line sensors (spectroscopy and / or microscopy observation) until fully formed, when they can be stored, until re-entry, for further analysis.
[0282] The real-time data can be used to inform kinetic / thermodynamic models for crystallization in microgravity and later terrestrial characterization can inform regarding crystal perfection, size range and yield. Furthermore, an exact replica of the in-orbit automated crystallization system can be built and run in parallel on Earth, allowing comparison of the benefits of microgravity crystallization. Several characteristics can be used to compare in-orbit and on-earth crystals, such as crystal size distribution, crystal purity, yield, nucleation, and crystal growth rate and can be conducted in collaboration with Diamond Light Source, Harwell.
[0283] Evaluating the impacts of the overall process, including launch, microgravity and re-entry can greatly inform on the challenges and the potential strategies to mitigate the impact on the biophysical properties of protein crystals.Useful Results and Outcomes
[0284] The primary goal of this experiment was to evaluate and validate that the benefits of microgravity observed in small scale can be replicated in large scale continuous crystallization set-up.
[0285] It was expected that the automated hardware would demonstrate the anticipated improved biophysical properties of protein crystals produced in microgravity. The outcomes of this experiment are both technical and commercial.
[0286] On the technical side, the wealth of data obtained can be used to: inform the design of next generation hardware, build kinetic / thermodynamic models of crystallization in microgravity, and elucidate the benefits as well as potential challenges of microgravity production that must be addressed.
[0287] Commercially, this experiment formed the foundation towards mass manufacture of protein crystal drugs to bring huge breakthroughs to cancer treatment. Not only could this experiment provide critical data to bring pharmaceutical companies on board but also lay the foundations for a future commercial relationship between the UK and Axiom.
[0288] The success of this mission promised rewarding breakthroughs for cancer treatment and the in-orbit manufacturing industry. Researchers have been aware of the proven benefits of protein crystallization in space but the development of hardware for commercial scale production onlymakes sense now that the infrastructure to support such a mission is in place. Furthermore, validation of in-orbit drug manufacture will pave the way for future research and innovation in space-based pharmaceutical processes.Example 2 — Experimental Protocol
[0289] An example methodology and fluid timeline is provided in FIG. 27. In this experimental protocol, the fluid flow parameters are defined in three settings: Setting A, Setting B, and Setting C. Before allowing for fluid flow, the fluid is stored in 2 L bags. Setting A provides fluid flow over 150 minutes at a rate of 0.5 mL / min, resulting in the flow of 75 mL of fluid. Setting B provides fluid flow over 150 minutes at a rate of 3 mL / min, resulting in the flow of 450 mL of fluid. Setting C provides fluid flow over 150 minutes at a rate of 5 mL / min, resulting in the flow of 750 mL of fluid. One cycle of the protocol consists of Setting A, Setting B, and Setting C, resulting in fluid flow for 450 minutes and allowing 1275 mL of fluid to travel through the PMU. In this protocol, the cycle is repeated three total times, resulting in a total volume of 3825 mL to travel through the PMU. In order to maintain fluid in the source, the 2L bag is switched between cycles, ensuring constant fluid flow.Computing systems
[0290] Referring to FIG. 23, a block diagram is shown depicting a machine that includes a computer system 600 (e.g., a processing or computing system) within which a set of instructions can execute for causing a device to perform or execute any one or more of the aspects and / or methodologies herein. The components in FIG. 23 are examples only and do not limit the scope of use or functionality of any hardware, software, embedded logic component, or a combination of two or more such components implementing particular embodiments.
[0291] Computer system 600 may include one or more processors 601, a memory 603, and a storage 608 that communicate with each other, and with other components, via a bus 640. The bus 640 may also link a display 632, one or more input devices 633 (which may, for example, include a keypad, a keyboard, a mouse, a stylus, etc.), one or more output devices 634, one or more storage devices 635, and various tangible storage media 636. All of these elements may interface directly or via one or more interfaces or adaptors to the bus 640. For instance, the various tangible storage media 636 can interface with the bus 640 via storage medium interface 626. Computer system 600 may have any suitable physical form, including but not limited to one or more integrated circuits (ICs), printed circuit boards (PCBs), mobile handheld devices (such as mobile telephones or PDAs), laptop or notebook computers, distributed computer systems, computing grids, or servers.
[0292] Computer system 600 includes one or more processor(s) 601 (e.g., central processing units (CPUs) or general-purpose graphics processing units (GPGPUs)) that carry out functions. Processor(s) 601 optionally contains a cache memory unit 602 for temporary local storage ofinstructions, data, or computer addresses. Processor(s) 601 are configured to assist in execution of computer readable instructions. Computer system 600 may provide functionality for the components depicted in FIG. 23 as a result of the processor(s) 601 executing non -transitory, processor-executable instructions embodied in one or more tangible computer-readable storage media, such as memory 603, storage 608, storage devices 635, and / or storage medium 636. The computer-readable media may store software that implements particular embodiments, and processor(s) 601 may execute the software. Memory 603 may read the software from one or more other computer-readable media (such as mass storage device(s) 635, 636) or from one or more other sources through a suitable interface, such as network interface 620. The software may cause processor(s) 601 to carry out one or more processes or one or more steps of one or more processes described or illustrated herein. Carrying out such processes or steps may include defining data structures stored in memory 603 and modifying the data structures as directed by the software.
[0293] The memory 603 may include various components (e.g., machine readable media) including, but not limited to, a random access memory component (e.g., RAM 604) (e.g., static RAM (SRAM), dynamic RAM (DRAM), ferroelectric random access memory (FRAM), phasechange random access memory (PRAM), etc.), a read-only memory component (e.g., ROM 605), and any combinations thereof. ROM 605 may act to communicate data and instructions unidirectionally to processor(s) 601, and RAM 604 may act to communicate data and instructions bidirectionally with processor(s) 601. ROM 605 and RAM 604 may include any suitable tangible computer-readable media described below. In one example, a basic input / output system 606 (BIOS), including basic routines that help to transfer information between elements within computer system 600, such as during start-up, may be stored in the memory 603.
[0294] Fixed storage 608 is connected bidirectionally to processor(s) 601, optionally through storage control unit 607. Fixed storage 608 provides additional data storage capacity and may also include any suitable tangible computer-readable media described herein. Storage 608 may be used to store operating system 609, executable(s) 610, data 611, applications 612 (application programs), and the like. Storage 608 can also include an optical disk drive, a solid-state memory device (e.g., flash-based systems), or a combination of any of the above. Information in storage 608 may, in appropriate cases, be incorporated as virtual memory in memory 603.
[0295] In one example, storage device(s) 635 may be removably interfaced with computer system 600 (e.g., via an external port connector (not shown)) via a storage device interface 625. Particularly, storage device(s) 635 and an associated machine-readable medium may provide nonvolatile and / or volatile storage of machine-readable instructions, data structures, program modules, and / or other data for the computer system 600. In one example, software may reside,completely or partially, within a machine-readable medium on storage device(s) 635. In another example, software may reside, completely or partially, within processor(s) 601.
[0296] Bus 640 connects a wide variety of subsystems. Herein, reference to a bus may encompass one or more digital signal lines serving a common function, where appropriate. Bus 640 may be any of several types of bus structures including, but not limited to, a memory bus, a memory controller, a peripheral bus, a local bus, and any combinations thereof, using any of a variety of bus architectures. As an example and not by way of limitation, such architectures include an Industry Standard Architecture (ISA) bus, an Enhanced ISA (EISA) bus, a Micro Channel Architecture (MCA) bus, a Video Electronics Standards Association local bus (VLB), a Peripheral Component Interconnect (PCI) bus, a PCI-Express (PCI-X) bus, an Accelerated Graphics Port (AGP) bus, HyperTransport (HTX) bus, serial advanced technology attachment (SATA) bus, and any combinations thereof.
[0297] Computer system 600 may also include an input device 633. In one example, a user of computer system 600 may enter commands and / or other information into computer system 600 via input device(s) 633. Examples of an input device(s) 633 include, but are not limited to, an alpha-numeric input device (e.g., a keyboard), a pointing device (e.g., a mouse or touchpad), a touchpad, a touch screen, a multi-touch screen, a joystick, a stylus, a gamepad, an audio input device (e.g., a microphone, a voice response system, etc.), an optical scanner, a video or still image capture device (e.g., a camera), and any combinations thereof. In some embodiments, the input device is a Kinect®, Leap Motion®, or the like. Input device(s) 633 may be interfaced to bus 640 via any of a variety of input interfaces 623 (e.g., input interface 623) including, but not limited to, serial, parallel, game port, USB, FIREWIRE, THUNDERBOLT, or any combination of the above.
[0298] In particular embodiments, when computer system 600 is connected to network 630, computer system 600 may communicate with other devices, specifically mobile devices and enterprise systems, distributed computing systems, cloud storage systems, cloud computing systems, and the like, connected to network 630. Communications to and from computer system 600 may be sent through network interface 620. For example, network interface 620 may receive incoming communications (such as requests or responses from other devices) in the form of one or more packets (such as Internet Protocol (IP) packets) from network 630, and computer system 600 may store the incoming communications in memory 603 for processing. Computer system 600 may similarly store outgoing communications (such as requests or responses to other devices) in the form of one or more packets in memory 603 and communicated to network 630 from network interface 620. Processor(s) 601 may access these communication packets stored in memory 603 for processing.
[0299] Examples of the network interface 620 include, but are not limited to, a network interface card, a modem, and any combination thereof. Examples of a network 630 or network segment 630 include, but are not limited to, a distributed computing system, a cloud computing system, a wide area network (WAN) (e.g., the Internet, an enterprise network), a local area network (LAN) (e.g., a network associated with an office, a building, a campus or other relatively small geographic space), a telephone network, a direct connection between two computing devices, a peer-to-peer network, and any combinations thereof. A network, such as network 630, may employ a wired and / or a wireless mode of communication. In general, any network topology may be used.
[0300] Information and data can be displayed through a display 632. Examples of a display 632 include, but are not limited to, a cathode ray tube (CRT), a liquid crystal display (LCD), a thin film transistor liquid crystal display (TFT-LCD), an organic liquid crystal display (OLED) such as a passive-matrix OLED (PMOLED) or active-matrix OLED (AMOLED) display, a plasma display, and any combinations thereof. The display 632 can interface to the processor(s) 601, memory 603, and fixed storage 608, as well as other devices, such as input device(s) 633, via the bus 640. The display 632 is linked to the bus 640 via a video interface 622, and transport of data between the display 632 and the bus 640 can be controlled via the graphics control 621. In some embodiments, the display is a video projector. In some embodiments, the display is a headmounted display (HMD) such as a VR headset. In further embodiments, suitable VR headsets include, by way of non-limiting examples, HTC Vive®, Oculus Rift®, Samsung Gear VR®, Microsoft HoloLens®, Razer OSVR®, FOVE VR®, Zeiss VR One®, Avegant Glyph®, Freefly VR® headset, and the like. In still further embodiments, the display is a combination of devices such as those disclosed herein.
[0301] In addition to a display 632, computer system 600 may include one or more other peripheral output devices 634 including, but not limited to, an audio speaker, a printer, a storage device, and any combinations thereof. Such peripheral output devices may be connected to the bus 640 via an output interface 624. Examples of an output interface 624 include, but are not limited to, a serial port, a parallel connection, a USB port, a FIREWIRE port, a THUNDERBOLT port, and any combinations thereof.
[0302] In addition or as an alternative, computer system 600 may provide functionality as a result of logic hardwired or otherwise embodied in a circuit, which may operate in place of or together with software to execute one or more processes or one or more steps of one or more processes described or illustrated herein. Reference to software in this present disclosure may encompass logic, and reference to logic may encompass software. Moreover, reference to a computer- readable medium may encompass a circuit (such as an IC) storing software for execution, a circuitembodying logic for execution, or both, where appropriate. The present disclosure encompasses any suitable combination of hardware, software, or both.
[0303] Various illustrative logical blocks, modules, circuits, and algorithm steps described in connection with the embodiments disclosed herein may be implemented as electronic hardware, computer software, or combinations of both. To clearly illustrate this interchangeability of hardware and software, various illustrative components, blocks, modules, circuits, and steps have been described above generally in terms of their functionality.
[0304] The various illustrative logical blocks, modules, and circuits described in connection with the embodiments disclosed herein may be implemented or performed with a general-purpose processor, a digital signal processor (DSP), an application specific integrated circuit (ASIC), a field programmable gate array (FPGA) or other programmable logic device, discrete gate or transistor logic, discrete hardware components, or any combination thereof designed to perform the functions described herein. A general-purpose processor may be a microprocessor, but in the alternative, the processor may be any conventional processor, controller, microcontroller, or state machine. A processor may also be implemented as a combination of computing devices, e.g., a combination of a DSP and a microprocessor, a plurality of microprocessors, one or more microprocessors in conjunction with a DSP core, or any other such configuration.
[0305] The steps of a method or algorithm described in connection with the embodiments disclosed herein may be embodied directly in hardware, in a software module executed by one or more processor(s), or in a combination of the two. A software module may reside in RAM memory, flash memory, ROM memory, EPROM memory, EEPROM memory, registers, hard disk, a removable disk, a CD-ROM, or any other form of storage medium. A storage medium is coupled to the processor such the processor can read information from, and write information to, the storage medium. In the alternative, the storage medium may be integral to the processor. The processor and the storage medium may reside in an ASIC. The ASIC may reside in a user terminal. In the alternative, the processor and the storage medium may reside as discrete components in a user terminal.
[0306] In accordance with the description herein, suitable computing devices include, by way of non-limiting examples, server computers, desktop computers, laptop computers, notebook computers, sub-notebook computers, netbook computers, netpad computers, set-top computers, media streaming devices, handheld computers, Internet appliances, mobile smartphones, tablet computers, personal digital assistants, video game consoles, and vehicles. Select televisions, video players, and digital music players with optional computer network connectivity are suitable for use in the system described herein. Suitable tablet computers, in various embodiments, include those with booklet, slate, and convertible configurations.
[0307] In some embodiments, the computing device includes an operating system configured to perform executable instructions. The operating system is, for example, software, including programs and data, which manages the device’s hardware and provides services for execution of applications. Suitable server operating systems include, by way of non-limiting examples, FreeBSD®, OpenBSD®, NetBSD®, Linux®, Apple® Mac OS X Server®, Oracle Solaris®, Windows Server®, and Novell NetWare®. Suitable personal computer operating systems include, by way of non-limiting examples, Microsoft Windows®, Apple Mac® OS X, UNIX®, and UNIX- like operating systems such as GNU / Linux®. In some embodiments, the operating system is provided by cloud computing. Suitable mobile smartphone operating systems include, by way of non-limiting examples, Nokia Symbian® OS, Apple® iOS, Research In Motion BlackBerry® OS, Google® Android®, Microsoft® Windows Phone® OS, Microsoft® Windows Mobile OS, Linux®, and Palm® WebOS. Suitable media streaming device operating systems include, by way of nonlimiting examples, Apple TV®, Roku®, Boxee®, Google TV®, Google Chromecast®, Amazon Fire®, and Samsung® HomeSync®. Suitable video game console operating systems include, by way of non-limiting examples, Sony® PS3®, Sony® PS4®, Microsoft® Xbox 360®, Microsoft Xbox One®, Nintendo Wii®, Nintendo Wii U®, and Ouya®. Suitable virtual reality headset systems include, by way of non-limiting example, Meta Oculus®.Non-transitory computer readable storage mediums
[0308] In some embodiments, the platforms, systems, media, and methods disclosed herein include one or more non-transitory computer readable storage media encoded with a program including instructions executable by the operating system of an optionally networked computing device. In further embodiments, a computer readable storage medium is a tangible component of a computing device. In still further embodiments, a computer readable storage medium is optionally removable from a computing device. In some embodiments, a computer readable storage medium includes, by way of non-limiting examples, CD-ROMs, DVDs, flash memory devices, solid state memory, magnetic disk drives, magnetic tape drives, optical disk drives, distributed computing systems including cloud computing systems and services, and the like. In some cases, the program and instructions are permanently, substantially permanently, semipermanently, or non-transitorily encoded on the media.Computer programs
[0309] In some embodiments, the platforms, systems, media, and methods disclosed herein include at least one computer program, or use of the same. A computer program includes a sequence of instructions, executable by one or more processor(s) of the computing device’s CPU, written to perform a specified task. Computer readable instructions may be implemented as program modules, such as functions, objects, Application Programming Interfaces (APIs),computing data structures, and the like, that perform particular tasks or implement particular abstract data types. In light of the present disclosure provided herein, a computer program may be written in various versions of various languages.
[0310] The functionality of the computer readable instructions may be combined or distributed as desired in various environments. In some embodiments, a computer program comprises one sequence of instructions. In some embodiments, a computer program comprises a plurality of sequences of instructions. In some embodiments, a computer program is provided from one location. In other embodiments, a computer program is provided from a plurality of locations. In various embodiments, a computer program includes one or more software modules. In various embodiments, a computer program includes, in part or in whole, one or more web applications, one or more mobile applications, one or more standalone applications, one or more web browser plug-ins, extensions, add-ins, or add-ons, or combinations thereof.Web applications
[0311] In some embodiments, a computer program includes a web application. In light of the present disclosure provided herein, a web application, in various embodiments, utilizes one or more software frameworks and one or more database systems. In some embodiments, a web application is created upon a software framework such as Microsoft® .NET or Ruby on Rails® (RoR). In some embodiments, a web application utilizes one or more database systems including, by way of non-limiting examples, relational, non-relational, object oriented, associative, and XML database systems. In further embodiments, suitable relational database systems include, by way of non-limiting examples, Microsoft® structured query language (SQL) Server, mySQL™, and Oracle®. A web application, in various embodiments, is written in one or more versions of one or more languages. A web application may be written in one or more markup languages, presentation definition languages, client-side scripting languages, server-side coding languages, database query languages, or combinations thereof. In some embodiments, a web application is written to some extent in a markup language such as Hypertext Markup Language (HTML), Extensible Hypertext Markup Language (XHTML), or extensible Markup Language (XML). In some embodiments, a web application is written to some extent in a presentation definition language such as Cascading Style Sheets (CSS). In some embodiments, a web application is written to some extent in a client-side scripting language such as Asynchronous Javascript and XML® (AJAX), Flash ActionScript, Javascript®, or Silverlight®. In some embodiments, a web application is written to some extent in a server-side coding language such as Active Server Pages® (ASP), ColdFusion®, Perl®, Java®, JavaServer Pages® (JSP), Hypertext Preprocessor® (PHP), Python®, Ruby®, Tel®, Smalltalk®, WebDNA®, or Groovy®. In some embodiments, a web application is written to some extent in a database query language such as Structured Query Language (SQL).In some embodiments, a web application integrates enterprise server products such as IBM Lotus Domino®. In some embodiments, a web application includes a media player element. In various further embodiments, a media player element utilizes one or more of many suitable multimedia technologies including, by way of non-limiting examples, Adobe® Flash®, HTML 5, Apple® QuickTime®, Microsoft Silverlight®, Java®, and Unity®.
[0312] Referring to FIG. 24, in a particular embodiment, an application provision system comprises one or more databases 700 accessed by a database management system (DBMS) 710. Suitable DBMSs include Firebird®, MySQL®, NoSQL®, PostgreSQL®, SQLite®, Oracle Database®, Microsoft SQL Server®, IBM DB2®, IBM Informix®, SAP Sybase®, SAP Sybase®, Teradata®, PostGIS®, Apache® Hive, Apache® Impala, time-series databases, graph databases, key-value storage, and the like. In this embodiment, the application provision system further comprises one or more application severs 720 (such as Java® servers, .NET® servers, PHP® servers, and the like) and one or more web servers 730 (such as Apache®, IIS®, GWS® and the like). The web server(s) optionally expose one or more web services via app application programming interfaces (APIs) 740. Via a network, such as the Internet, the system provides browser-based and / or mobile native user interfaces. In some cases, a DBMS may be a relational DBMS.
[0313] Referring to FIG. 25, in a particular embodiment, an application provision system alternatively has a distributed, cloud-based architecture 800 and comprises elastically load balanced, auto-scaling web server resources 810 and application server resources 820 as well synchronously replicated databases 830.Mobile applications
[0314] In some embodiments, a computer program includes a mobile application provided to a mobile computing device. In some embodiments, the mobile application is provided to a mobile computing device at the time it is manufactured. In other embodiments, the mobile application is provided to a mobile computing device via the computer network described herein.
[0315] In view of the present disclosure provided herein, a mobile application is created by techniques using hardware, languages, and development environments. Mobile applications are written in several languages. Suitable programming languages include, by way of non-limiting examples, C, C++, C#, Objective-C, Java®, Javascript®, Pascal®, Object Pascal®, Python™, Ruby®, VB.NET®, WML®, and XHTML / HTML with or without CSS, or combinations thereof.
[0316] Suitable mobile application development environments are available from several sources. Commercially available development environments include, by way of non-limiting examples, AirplaySDK®, alcheMo®, Appcelerator®, Celsius®, Bedrock®, Flash Lite®, .NET Compact Framework®, Rhomobile®, and WorkLight Mobile Platform®. Other development environmentsare available without cost including, by way of non-limiting examples, Lazarus®, MobiFlex®, MoSync®, and Phonegap®. Also, mobile device manufacturers distribute software developer kits including, by way of non-limiting examples, iPhone® and iPad® (iOS) SDK, Android® SDK, BlackBerry® SDK, BREW SDK, Palm® OS SDK, Symbian® SDK, webOS® SDK, and Windows® Mobile SDK.
[0317] Several commercial sources are available for distribution of mobile applications including, by way of non-limiting examples, Apple® App Store, Google® Play, Chrome® WebStore, BlackBerry® App World, App Store® for Palm devices, App Catalog® for webOS, Windows® Marketplace for Mobile, Ovi Store for Nokia® devices, Samsung® App s, and Nintendo® D Si Shop. Standalone applications
[0318] In some embodiments, a computer program includes a standalone application, which is a program that is run as an independent computer process, not an add-on to an existing process, e.g., not a plug-in. Standalone applications are often compiled. A compiler is a computer program(s) that transforms source code written in a programming language into binary object code such as assembly language or machine code. Suitable compiled programming languages include, by way of non-limiting examples, C, C++, Objective-C®, COBOL®, Delphi®, Eiffel®, Java®, Lisp®, Python®, Visual Basic®, and VB .NET®, or combinations thereof. Compilation is often performed, at least in part, to create an executable program. In some embodiments, a computer program includes one or more executable compiled applications. Additionally, microservices related to Python® and JavaScript® may be used.Web browser plug-ins
[0319] In some embodiments, the computer program includes a web browser plug-in (e.g., web extension, etc.). In computing, a plug-in is one or more software components that add specific functionality to a larger software application. Makers of software applications support plug-ins to enable third-party developers to create abilities which extend an application, to support easily adding new features, and to reduce the size of an application. When supported, plug-ins enable customizing the functionality of a software application. For example, plug-ins are commonly used in web browsers to play video, generate interactivity, scan for viruses, and display particular file types. Several web browser plug-ins may include Adobe Flash Player®, Microsoft Silverlight®, and Apple QuickTime®. In some embodiments, the toolbar comprises one or more web browser extensions, add-ins, or add-ons. In some embodiments, the toolbar comprises one or more explorer bars, tool bands, or desk bands.
[0320] In view of the present disclosure provided herein, several plug-in frameworks are available that enable development of plug-ins in various programming languages, including, by way of nonlimiting examples, C++, Delphi®, Java®, PHP®, Python®, and VB .NET®, or combinations thereof.
[0321] Web browsers (also called Internet browsers) are software applications, designed for use with network-connected computing devices, for retrieving, presenting, and traversing information resources on the World Wide Web. Suitable web browsers include, by way of non-limiting examples, Microsoft Internet Explorer®, Mozilla Firefox®, Google Chrome®, Apple Safari®, Opera Software Opera®, and KDE Konqueror®. In some embodiments, the web browser is a mobile web browser. Mobile web browsers (also called microbrowsers, mini-browsers, and wireless browsers) are designed for use on mobile computing devices including, by way of nonlimiting examples, handheld computers, tablet computers, netbook computers, subnotebook computers, smartphones, music players, personal digital assistants (PDAs), and handheld video game systems. Suitable mobile web browsers include, by way of non-limiting examples, Google Android® browser, RIM BlackBerry® Browser, Apple Safari®, Palm Blazer®, Palm WebOS® Browser, Mozilla Firefox® for mobile, Microsoft Internet Explorer Mobile®, Amazon Kindle Basic Web®, Nokia Browser®, Opera Software Opera Mobile®, and Sony PSP® browser.Software modules
[0322] In some embodiments, the platforms, systems, media, and methods disclosed herein include software, server, and / or database modules, or use of the same. In view of the present disclosure provided herein, software modules are created by techniques using machines, software, and languages. The software modules disclosed herein are implemented in a multitude of ways. In various embodiments, a software module comprises a file, a section of code, a programming object, a programming structure, or combinations thereof. In further various embodiments, a software module comprises a plurality of files, a plurality of sections of code, a plurality of programming objects, a plurality of programming structures, or combinations thereof. In various embodiments, the one or more software modules comprise, by way of non-limiting examples, a web application, a mobile application, and a standalone application. In some embodiments, software modules are in one computer program or application. In other embodiments, software modules are in more than one computer program or application. In some embodiments, software modules are hosted on one machine. In other embodiments, software modules are hosted on more than one machine. In further embodiments, software modules are hosted on a distributed computing platform such as a cloud computing platform. In some embodiments, software modules are hosted on one or more machines in one location. In other embodiments, software modules are hosted on one or more machines in more than one location.Databases
[0323] In some embodiments, the platforms, systems, media, and methods disclosed herein include one or more databases (DB), or use of the same. In view of the present disclosure provided herein, many databases are suitable for storage and retrieval data. In various embodiments,suitable databases include, by way of non-limiting examples, relational databases, non-relational databases, object-oriented databases, object databases, entity -relationship model databases, associative databases, XML databases, time-series databases, graph databases, and the like. Further non-limiting examples include SQL, PostgreSQL®, MySQL®, Oracle®, DB2®, and Sybase. In some embodiments, a database is internet-based. In further embodiments, a database is web-based. In still further embodiments, a database is cloud computing based. In a particular embodiment, a database is a distributed database. In other embodiments, a database is based on one or more local computer storage devices.
Claims
CLAIMSWHAT IS CLAIMED IS:
1. A method for crystallizing a substance in a microgravity environment, the method comprising:(a) receiving a plurality of reagents from at least one source into a reactor, wherein the reactor comprises at least one channel with at least a first portion and a second portion for processing the plurality of reagents;(b) contacting the plurality of reagents within the first portion, wherein the first portion comprises a plurality of periodic or non-periodic throttling nodes for optimizing a type of mixing of the plurality of reagents;(c) displacing the plurality of reagents using a first set of conditions when the plurality of reagents are within the first portion, wherein the first set of conditions is sufficient to cause the type of mixing of a subset of the plurality of reagents; and(d) contacting the subset of the plurality of reagents within the second portion, wherein the second portion comprises a uniform profile for optimizing crystallizing the subset of the plurality reagents using a second set of conditions sufficient to yield a crystallized substance having a set of crystallization characteristics.
2. The method of claim 1, further comprising storing the plurality of reagents in at least one container.
3. The method of claim 1 or 2, wherein a geometry of the throttling nodes is configured to support the type of mixing.
4. The method of any one of claims 1-3, wherein the plurality of reagents comprises a first reagent and a second reagent.
5. The method of any one of claims 1-4, wherein the first reagent comprises a precipitant solution and the second reagent comprises a substance solution.
6. The method of any one of claims 1-5, wherein the precipitant solution comprises a solution of zinc chloride, sodium citrate tribasic dihydrate, acetone, or a combination thereof.
7. The method of any one of claims 1-5, wherein the substance solution comprises a solution of a noncrystallized form or a crystal seed form of the substance.
8. The method of any one of claims 1-7, wherein the noncrystallized form of the substance comprises insulin.
9. The method of any one of claims 1-8, wherein the plurality of reagents further comprises a third reagent, a fourth reagent, or more reagents.
10. The method of any one of claims 1-9, further comprising pumping the plurality of reagents from the at least one source to the reactor using a set of pumping conditions.
11. The method of any one of claims 1-10, wherein the set of pumping conditions generates a constant flow rate of the plurality of reagents.
12. The method of any one of claims 1-10, wherein the set of pumping conditions generates a variable flow rate of the plurality of reagents.
13. The method of any one of claims 1-12, wherein the first set of conditions generates a constant displacement frequency or a constant displacement amplitude of the plurality of reagents.
14. The method of any one of claims 1-13, wherein the first set of conditions generates a nonconstant displacement frequency or a nonconstant displacement amplitude of the plurality of reagents.
15. The method of any one of claims 1-14, wherein the type of mixing is a diffusive mixing of the plurality of reagents.
16. The method of any one of claims 1-15, wherein the type of mixing is a convective mixing of the plurality of reagents.
17. The method of any one of claims 1-16, wherein the type of mixing is a turbulent mixing of the plurality of reagents.
18. The method of any one of claims 1-17, wherein the type of mixing is a convective mixing, a diffusive mixing, or a turbulent mixing of the plurality of reagents.
19. The method of any one of claims 1-18, wherein the first set of conditions and / or the second set of conditions accelerate mixing of the plurality of reagents by at least 5% compared to a different set of conditions.
20. The method of any one of claims 1-19, wherein the first set of conditions and / or the second set of conditions accelerate crystallizing of the plurality of reagents by at least 5% compared to a different set of conditions.
21. The method of any one of claims 1-20, wherein the first set of conditions or the second set of conditions improves at least one crystallization characteristic by at least 10% compared to a different set of conditions.
22. The method of any one of claims 1-21, further comprising detecting a signal from (i) the mixing in the first portion, (ii) the crystallizing in the second portion, or both.
23. The method of any one of claims 1-22, wherein the detecting comprises using an optical instrument to detect the signal.
24. The method of any one of claims 1-23, further comprising processing the signal to determine the crystallization characteristics.
25. The method of any one of claims 1-24, further comprising using one or more containers to store the crystallized substance or unreacted reagents.
26. The method of any one of claims 1-25, further comprising autonomously performing the method using a controller.
27. The method of any one of claims 1-26, further comprising iteratively adjusting the first set of conditions responsive to detecting a signal associated with the set of crystallization characteristics.
28. The method of any one of claims 1-27, further comprising iteratively adjusting the second set of conditions responsive to detecting a signal associated with the set of crystallization characteristics.
29. The method of any one of claims 1-28, wherein the microgravity environment is in low earth orbit (LEO), medium earth orbit (MEO), or geostationary Orbit (GEO).
30. The method of any one of claims 1-29, wherein the microgravity environment is in an orbit assigned to or controlled by a country or a jurisdiction, and wherein the country or the jurisdiction is the USA, Europe, Japan, China, the United Kingdom, Russia, or India.
31. The method of any one of claims 1-30, further comprising transporting the crystallized substance from the microgravity environment to a terrestrial environment or location.
32. The method of any one of claims 1-31, further comprising manufacturing a pharmaceutical drug from the crystallized substance in the microgravity environment or a terrestrial environment or location.
33. The method of any one of claims 1-32, further comprising processing the crystallized substance in the microgravity environment to yield a pharmaceutical drug, a pre-approved drug, or an agricultural compound.
34. The method of any one of claims 1-33, further comprising transporting the pharmaceutical drug from the microgravity environment to a terrestrial environment or location.
35. A crystalized substance produced by the method of any of claims 1-34.
36. A system for crystallizing a substance in a microgravity environment, the system comprising: at least one source configured to store a plurality of reagents for providing into a reactor, wherein the reactor comprises at least one channel with a first portion and a second portion for processing the plurality of reagents; a first pump configured to contact the plurality of reagents within the first portion, wherein the first portion comprises a plurality of periodic or non-periodic throttling nodes for optimizing a type of mixing of the plurality of reagents; an oscillator configured to displace the plurality of reagents using a first set of conditions when the plurality of reagents are within the first portion, wherein the first set of conditions is sufficient to cause the type of mixing of a subset of the plurality of reagents; and- n -a second pump configured to contact the subset of the plurality of reagents within the second portion, wherein the second portion comprises a uniform profile for optimizing crystallizing the subset of the plurality of reagents using a second set of conditions sufficient to yield a crystallized substance having a set of crystallization characteristics.
37. The system of claim 36, further comprising an observation module configured to detect a signal associated with the set of crystallization characteristics using an optical instrument.
38. The system of any one of claim 36-37, wherein the crystallized substance flows from the reactor to the observation module.
39. The system of any one of claims 36-38, wherein the observation module comprises an optical sensor configured to detect the signal when the oscillator is in a condition other than the first set of conditions.
40. The system of any one of claims 36-39, further comprising a storage container configured to hold the crystallized substance.
41. The system of any one of claims 36-40, wherein the at least one source comprises at least one container.
42. The system of any one of claims 36-41, wherein the plurality of reagents comprises a first reagent and a second reagent.
43. The system of any one of claims 36-42, wherein the first reagent comprises a precipitant solution and the second reagent comprises a substance solution.
44. The system of any one of claims 36-43, wherein the precipitant solution comprises zinc chloride, sodium citrate tribasic dihydrate, acetone, or a combination thereof.
45. The system of any one of claims 36-43, wherein the substance solution comprises a solution of a noncrystallized form of the substance.
46. The system of any one of claims 36-45, wherein the noncrystallized form of the substance comprises insulin.
47. The system of any one of claims 36-46, wherein the first pump is configured to generate a constant flow rate of the plurality of reagents.
48. The system of any one of claims 36-46, wherein the first pump is configured to generate a variable flow rate of the plurality of reagents.
49. The system of any one of claims 36-48, wherein the oscillator is configured to generate a constant displacement frequency or displacement amplitude of the of the plurality of reagents using the first set conditions.
50. The system of any one of claims 36-49, wherein the oscillator is configured to generate a nonconstant displacement frequency or displacement amplitude of the of the plurality of reagents using the first set of conditions.
51. The system of any one of claims 36-50, wherein the type of mixing is a convective mixing, diffusive mixing, or a turbulent mixing of the plurality of reagents.
52. The system of any one of claims 36-51, wherein the second pump is configured to generate a constant flow rate of the plurality of reagents using the second set of conditions.
53. The system of any one of claims 36-52, wherein the second pump is configured to generate a variable flow rate of the plurality of reagents using the second set conditions.
54. The system of any one of claims 36-53, wherein the first set of conditions and / or the second set of conditions accelerate mixing of the plurality of reagents by at least 5% compared to a different set of conditions.
55. The system of any one of claims 36-54, wherein the first set of conditions and / or the second set of conditions accelerate crystallizing of the plurality of reagents by at least 5% compared to a different set of conditions.
56. The system of any one of claims 36-55, wherein the system is positioned in a launch vehicle.
57. The system of any one of claims 36-56, wherein the microgravity environment is in low earth orbit (LEO), medium earth orbit (MEO), or geostationary Orbit (GEO).
58. The system of any one of claims 36-57, wherein the microgravity environment is in an orbit assigned to or controlled by a country or a jurisdiction, and wherein the country or the jurisdiction is the USA, Europe, Japan, China, the United Kingdom, Russia, or India.
59. The system of any one of claims 36-58, wherein the launch vehicle comprises the system and is configured for travel into the microgravity environment.
60. The system of any one of claims 36-59, wherein the first set of conditions and / or the second set of conditions improves at least one crystallization characteristic by at least 5% compared to a different set of conditions.
61. The system of any one of claims 36-60, wherein the system is configured to use a feedback loop to iteratively adjust the first set of conditions responsive to detecting a signal associated with the set of crystallization characteristics.
62. The system of any one of claims 36-61, wherein the system is configured to use a feedback loop to iteratively adjust the second set of conditions responsive to detecting a signal associated with the set of crystallization characteristics.
63. The system of any one of claims 36-62, wherein the second pump is the first pump.
64. A kit for use in a microgravity environment, the kit comprising at least: a first reagent; and a second reagent.
65. The kit of claim 64, wherein the first reagent comprises a precipitant solution.
66. The kit of any one of claims 64-65, wherein the precipitant solution comprises zinc chloride, sodium citrate tribasic dihydrate, acetone, or a combination thereof.
67. The kit of any one of claims 64-66, wherein the second reagent comprises a substance solution.
68. The kit of any one of claims 64-67, wherein the substance solution comprises a solution of a noncrystallized form or a crystal seed form of the substance.
69. The kit of any one of claims 64-68, wherein the noncrystallized form of the substance comprises insulin.
70. A launch vehicle comprising the kit of any one of claims 64-69.
71. The launch vehicle of claim 70, further comprising a rocket and a payload comprising the kit.
72. A kit for synthesizing a substance in a microgravity environment, the kit comprising at least: a first reagent; and a second reagent.
73. The kit of claim 72, wherein the first reagent comprises a precipitant solution.
74. The kit of any one of claims 72-73, wherein the precipitant solution comprises zinc chloride, sodium citrate tribasic dihydrate, acetone, or a combination thereof.
75. The kit of any one of claims 72-74, wherein the second reagent comprises a substance solution.
76. The kit of any one of claims 72-75, wherein the substance solution comprises a solution of a noncrystallized form or a crystal seed form of the substance.
77. The kit of any one of claims 72-76, wherein the noncrystallized form of the substance comprises insulin.
78. A launch vehicle comprising the kit of any one of claims 72-77.
79. The launch vehicle of claim 78, further comprising a rocket and a payload comprising the kit.
80. A method for transporting the kit of any one of claims 64-69 or 72-77 to a microgravity environment, the method comprising: securing the kit to a launch vehicle; and launching the launch vehicle to the microgravity environment from a terrestrial environment.
81. The method of claim 80, wherein the launch vehicle comprises a rocket and a payload.
82. The method of any one of claims 80-81, wherein the payload comprises the kit.
83. The method of any one or claims 80-82, wherein the microgravity environment is in low earth orbit (LEO), medium earth orbit (MEO), or geostationary Orbit (GEO).
84. The method of any one or claims 80-83, wherein the payload is in an orbit assigned to or controlled by a country or a jurisdiction, and wherein the country or the jurisdiction is the USA, Europe, Japan, China, the United Kingdom, Russia, or India.
85. A method for transporting a crystallized substance from a microgravity environment, the method comprising: securing the crystallized substance to an entry vehicle; and returning the entry vehicle from the microgravity environment to a terrestrial environment.
86. The method of claim 85, wherein the entry vehicle comprises a payload.
87. The method of any one of claims 85- 86, wherein the payload comprises the crystallized substance.
88. The method of any one of claims 85-87, wherein the payload is in low earth orbit (LEO), medium earth orbit (MEO), or geostationary Orbit (GEO) prior to returning from the microgravity environment.
89. The method of any one or claims 85-88, wherein the payload is in an orbit assigned to or controlled by a country or a jurisdiction, and wherein the country or the jurisdiction is the USA, Europe, Japan, China, the United Kingdom, Russia, or India prior to returning from the microgravity environment.
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