Fluid handling systems and methods

Abstract

1. A fluid handling system comprising a fluid pathway system comprising a first fluid pathway for guiding a first fluid material towards a mixing region of the fluid pathway system and a second fluid pathway for guiding a second fluid material towards the mixing region, the mixing region being arranged in fluid communication with the first fluid pathway and the second fluid pathway such that the first fluid material and the second fluid material can mix in the mixing region to form a fluid material mixture, the fluid handling system comprising a non-guiding flow region, the non-guiding flow region being capable of, or configured to, prevent contact of the fluid material mixture with internal walls suitable for guiding the flow of the fluid material mixture along a flow direction of the fluid material mixture while the fluid material mixture moves through the non-guiding flow region, and the non-guiding flow region extending for a predetermined distance downstream of the mixing region, for example extending for only a predetermined distance.

Description

[Technical Field]

[0001] The present disclosure relates to improvements relating to fluid handling systems and methods for processing fluids in fluid handling systems. [Background technology]

[0002] It is an object of the present disclosure to provide an improved fluid handling system for processing fluids, for example for mixing at least two fluids together. The improvements may also relate to methods for processing fluids, as well as to uses of the fluid handling system for processing fluids and fluid substance mixtures obtained from the fluids.

[0003] These and / or other objects, as will become apparent from the following description, are achieved by the subject matter disclosed herein and / or as set forth in the accompanying independent claims. Advantageous embodiments and refinements are the subject matter of, inter alia, the dependent claims. Summary of the Invention

[0004] A first aspect of the present disclosure relates to a fluid handling system for processing a first fluid substance and a second fluid substance to provide or form a fluid substance mixture. Another aspect of the present disclosure relates to a method for processing a fluid, optionally for a fluid substance mixture, for example by mixing a first fluid substance and a second fluid substance. The method can be performed using the fluid handling system of the first aspect; however, other fluid handling systems are also applicable. Another aspect of the present disclosure relates to the use of a fluid handling system for providing a fluid substance mixture, for example by mixing a first fluid substance and a second fluid substance and / or by using a method described herein. The fluid handling system can be a fluid handling system of the first aspect.

[0005] It should be noted that features disclosed herein in relation to a method also apply to the fluid handling system and / or use, and features disclosed herein for the use or fluid handling system also apply to the method. In general, features disclosed in relation to different aspects, examples or embodiments can be combined with each other, even if such combination is not explicitly described herein. Unless expressly stated otherwise, features disclosed herein above and below apply to all aspects, examples or embodiments of the present disclosure, e.g., fluid handling systems, methods and uses. For example, where features similar to a method are described, they should be understood to also relate to a fluid handling system configured to perform or implement these features, e.g., a fluid handling system configured to or capable of providing flow to a mixing region (e.g., in a manner equivalent to that described below in relation to the fluid handling system).

[0006] In one embodiment, the fluid handling system comprises a fluid pathway system. The fluid pathway system comprises a first fluid pathway for directing a first fluidic substance (also referred to herein as the first fluid) to a mixing region of the fluid pathway system. The fluid pathway system further comprises a second fluid pathway for directing a second fluidic substance (also referred to herein as the second fluid) to the mixing region. The fluid pathway system may also comprise further fluid pathways for directing a further fluidic substance to the mixing region of the fluid pathway system, for example a third fluid pathway for directing a third fluidic substance, for example a gas such as air, to the mixing region of the fluid pathway system.

[0007] In the following, the fluid handling system will be described in terms of a fluid pathway system comprising a first fluid pathway for a first fluid substance and a second fluid pathway for a second fluid substance, respectively, however the system is not limited to only two fluid substances and features relating to the first fluid pathway and / or the second fluid pathway and / or the first fluid substance and / or the second fluid substance also apply to further fluid pathways and / or fluid substances, for example a third fluid pathway and / or a third fluid substance.

[0008] The mixing region is arranged to be in fluid communication with the first fluid path and the second fluid path, e.g., simultaneously, so that the first fluid substance and the second fluid substance can mix in the mixing region to form a fluid substance mixture. Up to the mixing region, the fluid paths are conveniently fluidly separated from one another. The fluid handling system may consist of or comprise a fluid path system. The present disclosure also relates to such a fluid path system.

[0009] The mixing region can be configured, for example, by its shape and / or location relative to the first and second fluid paths, to allow mixing of the first and second fluid materials. The first and second fluids can flow into the mixing region simultaneously.

[0010] In one embodiment, the fluid handling system comprises a non-guiding flow region. The non-guiding flow region can or is configured such that contact of the fluid material mixture with internal walls suitable for guiding the flow of the fluid material mixture along the flow direction of the fluid material mixture is prevented while the fluid material mixture moves through the non-guiding flow region. This can be achieved by various means. One example is to widen the fluid path so that the fluid flow cannot contact internal walls of the fluid path system. Thus, although there may be internal walls that define the fluid path laterally, for example circumferentially relative to the flow direction, the fluid flow (of the fluid material mixture) does not contact the internal walls while passing through the non-guiding flow region. Another example is to interrupt the fluid path system at the non-guiding flow region. In this case, there are no internal walls that the fluid flow (of the fluid material mixture) could come into contact with.

[0011] In one embodiment, the non-guiding flow region extends for a predetermined distance, e.g., only a predetermined distance, downstream of the mixing region. The non-guiding flow region may be a region of a fluid handling system, e.g., a fluid path system, through which a fluid material mixture can flow in an unguided manner (e.g., freely). The fluid handling system may be configured such that the fluid material mixture is not directional guided as it flows through the non-guiding flow region. The flow direction of the fluid material mixture in the non-guiding flow region may be determined (or determined solely) by the direction the material mixture had when it entered the non-guiding flow region and by gravity (e.g., gravity alone) when the fluid material mixture is within the non-guiding flow region. Thus, in the non-guiding flow region during operation or use of the fluid handling system, all directional changes (if any) of fluid flow relative to the fluid path system may be governed by gravity. In the non-guiding flow region, there is preferably no contact between the fluid material mixture and the interior walls of the fluid path system.

[0012] In other words, in the present disclosure, any change in the direction of flow of the fluid material mixture within the non-guiding flow region and / or at least within a predetermined distance of the non-guiding flow region may be obtained through gravity (e.g., gravity alone) acting on the fluid material mixture.

[0013] A fluid substance mixture in the sense of the present disclosure can be a fluid substance, e.g., a liquid, resulting from the mixing of at least two fluid substances, e.g., a first fluid substance and a second fluid substance.

[0014] The non-guiding flow region has been found to be particularly advantageous for fluid substance mixtures that exhibit, for example, a transitional or intermediate state, for example, immediately after the fluid substances have been mixed for the fluid substance mixture. After the (temporary) intermediate or transitional state, the fluid substance mixture may assume a final state. A transitional state may be a state in which the final and / or stable physicochemical properties of the fluid substance mixture have not yet been established. In the final state, the fluid substance mixture may have stable, e.g., constant, properties. The final state may be a stable state. In the transitional or intermediate state, the fluid substance mixture may exhibit a higher tendency to deposit on the inner walls of the fluid path.

[0015] During a transitional state of a fluid substance mixture, contact of the fluid substance mixture with any element may increase the likelihood of undesirable changes in the physicochemical properties of the fluid substance mixture. Therefore, it has been found advantageous to provide a non-guiding flow region extending over a predetermined distance in which the fluid substance mixture does not contact any wall, e.g., any inner wall of a fluid path system, during the transitional period or state. For example, a fluid substance mixture used during the production of a nanoparticle composition may have an increased tendency to deposit on the inner wall of a fluid path system immediately after nanoparticle formation conditions are established, e.g., by mixing a first fluid substance mixture with a second fluid substance mixture. Therefore, the predetermined distance is conveniently selected so that the transitional state during nanoparticle formation, which has a high affinity for the surface and, e.g., a high tendency to form deposits on the surface, is completed before contacting the inner wall, e.g., before the non-guiding flow region ends.

[0016] The nanoparticle composition can be any particle composed of a mixture of at least one lipid and / or at least one polymer, such as (ionizable) lipid or liposomal nanoparticles (LNP), (ionizable) lipoplexes (LPX), (ionizable) polyplexes (PPX).

[0017] According to at least one embodiment a fluid directing or retaining element of the fluid handling system is positioned downstream of the non-directing flow region to receive and / or direct the fluid material mixture.

[0018] The fluid material mixture should not be in a transitional or intermediate state when received and / or guided by the fluid directing element or when received by the fluid retaining element, and therefore, when the fluid material mixture passes through the non-guiding flow region, the fluid material mixture is preferably in its steady state.

[0019] According to at least one embodiment the fluid handling system is configured to allow a first fluidic substance and a second fluidic substance to move simultaneously into the mixing region, where the substances may be mixed immediately upon entering the mixing region.

[0020] According to at least one embodiment, the diameter (e.g., maximum, minimum, or average diameter) of the first fluid pathway and / or the diameter (e.g., maximum, minimum, or average diameter) of the second fluid pathway is 0.5 mm or more and / or 5.5 cm or less. The diameter can be any one or more of the following: 0.5 mm, 1 mm, 1.5 mm, 2 mm, 3 mm, 4 mm, 5 mm, 6 mm, 7 mm, 8 mm, 9 mm, 10 mm, 15 mm, 20 mm, 25 mm, 30 mm, 35 mm, 40 mm, 45 mm, 50 mm, 55 mm. Alternatively or additionally, the diameter can be any one or less of the following: 0.5 mm, 1 mm, 1.5 mm, 2 mm, 3 mm, 4 mm, 5 mm, 6 mm, 7 mm, 8 mm, 9 mm, 10 mm, 15 mm, 20 mm, 25 mm, 30 mm, 35 mm, 40 mm, 45 mm. The diameter of the first fluid pathway and / or the diameter of the second fluid pathway can be between 0.5 mm and 45 mm. The diameter of the first fluid pathway and / or the diameter of the second fluid pathway can be equal to or greater than 15.6 mm and / or equal to or less than 12.8 mm. The diameter of the first fluid pathway and / or the diameter of the second fluid pathway can be 50.8 mm.

[0021] According to at least one embodiment, the diameter (e.g., maximum, minimum, or average diameter) of the first fluid path and / or the diameter (e.g., maximum, minimum, or average diameter) of the second fluid path is greater than or equal to 1 / 32 inch and / or less than or equal to 2 inches, measured in fractional inches (e.g., SAE (Standard Automotive Engineers)). The diameter can be any one or more of the following: 1 / 32 inch, 1 / 16 inch, 1 / 8 inch, 1 / 4 inch, 3 / 4 inch, 1 / 2 inch, 1 inch, 1 1 / 32 inches, 1 1 / 16 inches, 1 1 / 8 inches, 1 1 / 4 inches, 1 3 / 4 inches, 1 1 / 2 inches, 2 inches. Alternatively or additionally, the diameter may be any one of the following or less: 1 / 32 inch, 1 / 16 inch, 1 / 8 inch, 1 / 4 inch, 3 / 4 inch, 1 / 2 inch, 1 inch, 1 1 / 32 inches, 1 1 / 16 inches, 1 1 / 8 inches, 1 1 / 4 inches, 1 3 / 4 inches, 1 1 / 2 inches, 2 inches.

[0022] The diameter of the first fluid pathway and the diameter of the second fluid pathway may be equal to or different from one another.

[0023] According to at least one embodiment, the fluid flow of the first fluid material along the first fluid pathway can be or is driven by a first flow driver, for example a pump such as a syringe pump, a peristaltic pump, a diaphragm pump and / or a piston pump, or a pressurized vessel.

[0024] According to at least one embodiment, the fluid flow of the second fluid material along the second fluid pathway can be or is driven by a second flow driver, for example a pump such as a syringe pump, a peristaltic pump, a diaphragm pump and / or a piston pump, or a pressurized vessel.

[0025] According to at least one embodiment, the fluid flow of the fluid material mixture downstream of the non-guided flow region can be or is driven by a mixture flow driver, for example, a pump such as a syringe pump, a peristaltic pump, a diaphragm pump and / or a piston pump, or a pressurized vessel.

[0026] According to at least one embodiment, the fluid path system includes a directing region. The directing region can be disposed between the mixing region and the non-guiding flow region, as viewed along the flow direction of the fluid material mixture. The directing region can be configured to determine an inlet flow direction of the fluid material mixture as it enters the non-guiding flow region. In this manner, the flow of the fluid material mixture can be directed into the non-guiding flow region to ensure that the fluid material mixture avoids contact with a wall, e.g., an inner wall, of the non-guiding flow region.

[0027] According to at least one embodiment, the orientation region has a length of less than or equal to one of the following values: 10cm, 9cm, 8cm, 7cm, 6cm, 5cm, 4cm, 3.5cm, 3cm, 2.5cm, 2cm, 1.5cm, 1cm, 0.5cm, 0.4cm, 0.3cm, 0.2cm, 0.1cm.

[0028] According to at least one embodiment, the orientation region has a length of one or more of the following values: 0.05 cm, 0.1 cm, 0.2 cm, 0.5 cm, 1 cm, 1.5 cm, 2 cm, 2.5 cm, 3 cm, 3.5 cm, 4 cm, 5 cm, 6 cm, 7 cm, 8 cm, 9 cm, 10 cm.

[0029] The orientation region may have a length between 0.05 cm and 10 cm. In particular, the orientation region may have a length of 2.2 cm.

[0030] According to at least one embodiment, the inlet flow direction is parallel to the major axis of the non-guided flow region.

[0031] According to at least one embodiment, the inlet flow direction is at an angle to the major axis of the non-guided flow region.

[0032] In both cases, e.g., parallel or angled, the directing region is positioned such that the fluid material mixture exiting the directing region flows into the non-guiding flow region, thereby preventing contact with an interior wall suitable for directing flow in the non-guiding flow region.

[0033] According to at least one embodiment, the fluid path of the fluid path system directing the fluid material mixture widens along the flow direction away from the mixing region, for example at the end of the directing region, when viewed along the flow direction from the mixing region towards the non-directing flow region.

[0034] According to at least one embodiment, for example at a predetermined distance, the fluid handling system has a free fall or free flow region, for example due to an interruption of the fluid path system in the non-guiding flow region and / or because the mixture fluid path of the fluid path system is configured with an appropriate width in the non-guiding flow region. The free flow region may allow the fluid material mixture to move within the fluid handling system without contacting an internal wall of the fluid handling system, for example the internal wall closest to the fluid material mixture.

[0035] According to at least one embodiment, the fluid pathway system defines a first flow direction for a first fluid material flow from a first fluid pathway through a first inlet into the mixing region, and the fluid pathway system defines a second flow direction for a second fluid material flow from a second fluid pathway through a second inlet into the mixing region. The first and second flow directions may define an angle. The angle may be, for example, in the range between 45° and 315°, for example, between 60° and 300°, for example, between 120° and 270°, or about 180°.

[0036] According to at least one embodiment, the mixing region can include more than one, e.g., two, first inlets for a first fluid path for a first fluid material and / or more than one, e.g., two, second inlets for a second fluid path for a second fluid material mixture. Thus, the mixing region can have, for example, three inlets through which the first and second fluid materials enter the mixing region, e.g., two first inlets for the first fluid material and one second inlet for the second fluid material. In embodiments in which the mixing region includes more than one first inlet and / or more than one second inlet for each of the first and second fluid materials, the first and second fluid materials can be moved through the mixing region simultaneously.

[0037] According to at least one embodiment, the mixing zone may comprise one or more further inlets for further fluid paths for further fluid substances, e.g., one or more third inlets for a third fluid path for a third fluid substance, e.g., air.

[0038] All features of the first fluid path and / or second fluid path and the first fluid material and / or second fluid material described herein that correlate to embodiments in which the mixing region has one first inlet for the first fluid material and one second inlet for the second fluid material may also apply to embodiments in which the mixing region has one or more first inlets and / or one or more second inlets and / or one or more further inlets, for example a third inlet.

[0039] According to at least one embodiment, the mixing region has an outlet for the fluid material mixture and / or the non-guided flow region comprises an inlet region.

[0040] According to at least one embodiment, the inner diameter of the exit or entrance region is greater than or equal to 0.5 mm and less than or equal to 6 cm, for example between 1 mm and 5.2 cm.

[0041] The inner diameter of the outlet or inlet region can be 0.5 mm, 5 mm, 10 mm, 15 mm, 20 mm, 25 mm, 30 mm, 35 mm, 40 mm, 45 mm, 50 mm, 55 mm, 60 mm or more. The inner diameter of the outlet or inlet region can be 60 mm, 55 mm, 50 mm, 45 mm, 40 mm, 35 mm, 30 mm, 25 mm, 20 mm, 15 mm, 10 mm, 5 mm, 0.5 mm or less. For example, 52 mm or less.

[0042] The inner diameter of the outlet or inlet region may for example be between 1 mm and 60 mm, for example between 30 mm and 52 mm.

[0043] According to at least one embodiment, the inlet area of ​​the non-guiding flow region is adjacent to or coincident with the outlet of the directing region.

[0044] If the fluid handling system does not comprise a directing region, the inlet region of the non-guiding flow region is adjacent to or coincident with the outlet of the mixing region, in such a case the outlet of the mixing region may be positioned such that the fluid material mixture exiting the outlet of the mixing region flows into the non-guiding flow region such that contact with internal walls suitable for directing flow within the non-guiding flow region is prevented.

[0045] According to at least one embodiment, the predetermined distance is any one or more of the following values: 5 cm, 6 cm, 7 cm, 8 cm, 9 cm, 10 cm, 11 cm, 12 cm, 13 cm, 20 cm, 35 cm, 50 cm, 80 cm, 100 cm, 200 cm. Alternatively, or additionally, the predetermined distance is any one or less of the following values: 600 cm, 565 cm, 550 cm, 500 cm, 450 cm, 400 cm, 300 cm, 200 cm, 165 cm, 68 cm, 35 cm, 30 cm, 25 cm, 20 cm, 15 cm, 13 cm. Thus, the predetermined distance can be between 5 cm and 565 cm or 600 cm, for example, between 5 cm and 13 cm.

[0046] According to at least one embodiment, the predetermined distance is selected such that, for example, at a predetermined flow rate of the substance mixture, the fluid substance mixture has most or all of its intermediate or transition state within the non-guided flow region.

[0047] According to at least one embodiment, the predetermined distance is selected so that the fluid material mixture travels through the non-guided flow region for at least a predetermined time. The predetermined time may be a time characteristic representing the time required for the fluid material mixture to reach a steady state or final state. For example, the predetermined time may be longer than the time required to reach the steady state or final state, or may be longer than 80% of the time required for the fluid material mixture to reach its steady state.

[0048] According to at least one embodiment, the predetermined time is one or less of the following: 1 second, 950 milliseconds, 900 milliseconds, 850 milliseconds, 800 milliseconds, 750 milliseconds, 700 milliseconds, 650 milliseconds, 600 milliseconds, 550 milliseconds, 500 milliseconds, 450 milliseconds, 400 milliseconds.

[0049] According to at least one embodiment, the predetermined time is one or more of the following: 1 millisecond, 5 milliseconds, 10 milliseconds, 20 milliseconds, 25 milliseconds, 50 milliseconds, 100 milliseconds, 150 milliseconds, 200 milliseconds, 300 milliseconds.

[0050] According to at least one embodiment the fluid handling system has a density of 1 g / cm 3 For water having a viscosity of 1 cP and a temperature of 20°C, the flow path is configured to be operated at a flow rate and / or have a flow path diameter such that the relationship between the flow rate and the flow path diameter results in a flow at the mixing region, directing region, first inlet, second inlet, and / or outlet (e.g., the outlet of the mixing region) characterized by a calculated Reynolds number (Re) of one or more of the following values: 500, 1000, 1100, 1200, 1300, 1400, 1500, 1700, 1800, 1900, 2000.

[0051] According to at least one embodiment the fluid handling system has a density of 1 g / cm 3 For water having a viscosity of 1 cP and a temperature of 20°C, the flow path is configured to be operated at a flow rate and / or have a flow path diameter such that the relationship between the flow rate and the flow path diameter results in a flow at the mixing region, directing region, first inlet, second inlet, and / or outlet (e.g., outlet of the mixing region) characterized by a calculated Reynolds number (Re) of less than or equal to one of the following values: 10,000, 7,500, 5,000, 4,000, 3,000, 2,900, 2,800, 2,700, 2,600, 2,500.

[0052] According to at least one embodiment the fluid handling system is capable of handling or providing a fluid flow, e.g. in the mixing region, directing region, first inlet, second inlet and / or outlet, having a Reynolds number (Re) of between 500 and 10,000, such as between 500 and 3,000, for example between 1,700 and 2,500.

[0053] The Reynolds number is used to classify fluid flows, such as liquid flows. The Reynolds number, R, of a fluid flow can be calculated using the following formula: TIFF2026505079000002.tif8170where V is the velocity of the fluid flow in m / s (meters per second), D is the characteristic distance in m (meters) (e.g., the diameter of the flow channel that directs the fluid flow, e.g., the inner diameter of a conduit), and Vis_kin is m 2 / s. Kinematic viscosity is the ratio of the fluid's (dynamic) viscosity (Vis_kin) in Pascal seconds (Pa s) to the fluid's density D_L (e.g., kg / m 3 ) The velocity V can be derived from the flow rate (specified, for example, in ml / min (milliliters per minute)) by dividing the flow rate by the cross-sectional area of ​​the channel directing the fluid flow. The cross section is taken perpendicular to the direction of flow. For a circular cross section, the cross-sectional area is (ID / 2) 2 *π, where ID is the inner diameter of the flow passage, e.g., of an outlet, conduit or tube.

[0054] To determine the Reynolds number of the fluid flow leaving the mixing region and / or at the outlet of the mixing region or mixing component, the characteristic values ​​of the first and second fluids can be used (weighted, if applicable, by a coefficient that determines the contribution of the flow rates of the first and second fluids into the mixing chamber to the total flow rate of the first and second fluids). Thus, the Reynolds number of each of the fluid material mixture flows considered herein can be related to a Reynolds number based on the values ​​of the relevant quantities calculated as set forth below, or to a Reynolds number based on the values ​​of the relevant quantities measured.

[0055] After the fluid material mixture, i.e., the first fluid material and the second fluid material are mixed, the Reynolds number is: TIFF2026505079000003.tif8170 can be used to calculate the D is the inner diameter of the flow channel at the relevant location, e.g., at the outlet of the mixing region; F_1 is the flow rate of the first fluid material into the mixing region; and F_2 is the flow rate of the second fluid material into the mixing region (the sum of F_1 and F_2 is the flow rate of the fluid material mixture at the outlet of the mixing region).

[0056] TIFF2026505079000004.tif8170 where, Vis_1 is the (dynamic) viscosity of the first fluid substance, Vis_2 is the dynamic viscosity of the second fluid material.

[0057] TIFF2026505079000005.tif8170 where, D_1 is the density of the first fluid material, D_2 is the density of the second fluid material.

[0058] TIFF2026505079000006.tif7170Then, the Reynolds number is obtained from the following formula: TIFF2026505079000007.tif8170

[0059] The Reynolds number is a dimensionless quantity that can be used to qualify fluid flow without having to specify conduit dimensions or other values ​​that characterize the flow, such as flow rate, viscosity, density, etc.

[0060] According to at least one embodiment, the first fluid material and the second fluid material are selected such that the fluid material mixture resulting from mixing the first fluid material and the second fluid material is in an intermediate state, for example, during and / or immediately after mixing of the first fluid material and the second fluid material.

[0061] According to at least one embodiment, the intermediate state is a temporary state, eg, a state that exists for less than a predetermined period of time.

[0062] According to at least one embodiment, after the intermediate state, the fluid material mixture assumes a steady state.

[0063] According to at least one embodiment, a fluid material mixture in an intermediate state has a greater tendency to form deposits on walls, eg, interior walls defining a fluid pathway, than in a steady state.

[0064] The intermediate state is sometimes colloquially referred to as the "sticky phase" because it is a state in which the fluid mixture tends to form deposits on the walls (i.e., "stick") and may cause clogging of any tubing through which it passes in the intermediate state. As the processed volume increases, the flow path may become blocked in the intermediate state, for example, by completely clogging the tubing through which it passes, which may unintentionally block or damage the production process of the fluid material mixture. This limits the volume that can be processed in a given fluid path system. Therefore, it is advantageous to avoid or mitigate clogging, such as by providing non-guided flow regions.

[0065] Furthermore, some of the deposits may detach during processing, which can cause changes in the size distribution of the nanoparticles over time (e.g., non-uniform size distribution), which is obviously detrimental to the final product (e.g., fluid material mixture).

[0066] It may be advantageous to provide a non-guided flow region in a fluid handling system in which the fluid material mixture does not contact any walls, e.g. any internal walls, during its intermediate state, e.g. viscous phase (or at least during, e.g. most of, its intermediate state), thereby minimizing the formation of deposits and the possibility of clogging. This may increase productivity during processing, result in a more homogeneous end product with a uniform particle size distribution, and reduce defects in or during the manufacturing process.

[0067] This may be achieved, for example, by a non-guided flow region, eg, a free-fall region, in which the fluid material mixture is prevented from contacting the walls (eg, the inner walls of the non-guided flow region).

[0068] According to at least one embodiment the fluid handling system is configured to cause the fluid material mixture to flow through the non-guided flow region in, or at least during, its intermediate state.

[0069] According to at least one embodiment the fluid handling system is configured and / or operable to allow the fluid material mixture, in its intermediate state, to flow only through the mixing region and / or the non-guided flow region and / or optionally the directing region.

[0070] According to at least one embodiment, the first fluid material and the second fluid material are selected to form a fluid material mixture comprising colloids having an average particle size, e.g., greater than or equal to 10 nm and / or less than or equal to 1000 nm, e.g., between 200 nm and 500 nm, e.g., about 400 nm. According to at least one embodiment, the average particle size can be greater than or equal to 250 nm and / or less than or equal to 750 nm. According to at least one embodiment, the average particle size can be greater than or equal to 60 nm and / or less than or equal to 140 nm. According to at least one embodiment, the average particle size can be greater than or equal to 50 nm and / or less than or equal to 150 nm. According to at least one embodiment, the average particle size can be greater than or equal to 10 nm and / or less than or equal to 300 nm.

[0071] According to at least one embodiment, the first and second fluid materials are selected to form a fluid material mixture containing colloids having an average particle size of, for example, 10 nm, 20 nm, 50 nm, 100 nm, 250 nm, 300 nm, 350 nm, 400 nm, 450 nm, 500 nm, 600 nm, 650 nm, 700 nm or more. Additionally or alternatively, the first and second fluid materials are selected to form a fluid material mixture containing colloids having an average particle size of, for example, 750 nm, 700 nm, 650 nm, 600 nm, 550 nm, 500 nm, 450 nm, 400 nm, 350 nm, 300 nm, 250 nm, 200 nm, 150 nm, 100 nm, 50 nm, 20 nm or less. The particle size may depend on the starting material used.

[0072] According to at least one embodiment the fluid handling system may be operated with a processing volume of 50 mL or more, such as 100 mL, 200 mL, 500 mL, 700 mL or more, or even 900 mL or 1 L or more, or even 10 L or 20 L or more, for example 12 L or 12.2 L, or even 50 L or 100 L or more, or even 500 L or 1000 L or more.

[0073] According to at least one embodiment the fluid handling system may be operated with a processing volume of up to 1000 L, 500 L, 100 L, 50 L, 20 L, such as up to 500 L, 400 L, 300 L, 12 L, 10 L, 2 L, 1 L, 700 mL, 500 mL, 200 mL, or even up to 100 mL or 50 mL.

[0074] The fluid handling system may be operated with a processing volume of 50 mL to 20 L, for example between 2 L and 20 L, for example 12.2 L.

[0075] However, the fluid handling system is not limited to any of these processing capacities and may, for example, have a processing capacity in excess of 1000L.

[0076] According to at least one embodiment, the process is continuous, thereby providing a theoretically unlimited processing capacity, eg, increasing processing capacity as long as the system is operated.

[0077] According to at least one embodiment, the first fluidic substance comprises an ionic and / or ionizable substance.

[0078] According to at least one embodiment, the second fluid material comprises an ionic and / or ionizable material.

[0079] According to at least one embodiment, the ionic material is a cationic or anionic material, or a cationic and anionic material, such as a zwitterionic material.

[0080] According to at least one embodiment, the ionizable substance is a cationic ionizable substance or an anionic ionizable substance, or both a cationic and anionic ionizable substance, such as a zwitterionic ionizable substance.

[0081] According to at least one embodiment, the ionic material of the first fluid material is an anionic material and the ionic material of the second fluid material is a cationic material.

[0082] According to at least one embodiment, the first fluid material comprises a polymeric material, for example a polymeric ionic material.

[0083] According to at least one embodiment, the first fluidic substance comprises a nucleic acid, a peptide, or a protein.

[0084] According to at least one embodiment, the first fluid substance comprises RNA, such as mRNA, and optionally, the first fluid substance is an RNA solution.

[0085] According to at least one embodiment, the second fluid material is a colloidal suspension, such as an ionic colloidal suspension, such as a cationic colloidal suspension.

[0086] According to at least one embodiment, the second fluid substance comprises a hydrophilic and / or lipophilic substance, eg, an amphiphilic substance.

[0087] According to at least one embodiment, the second fluid substance comprises at least one lipid, for example a mixture of lipids.

[0088] According to at least one embodiment, the second fluid substance comprises a liposome.

[0089] According to at least one embodiment, the second fluid material comprises a cationic polymer.

[0090] For example, but not by way of limitation, the second fluid material may be: (i) an ionizable lipid, preferably an ionizable cationic lipid, such as an ionizable cationic amino lipid, such as ALC-0315 ((4-hydroxybutyl)azanediyl)bis(hexane-6,1-diyl)bis(2-hexyldecanoate)), or SM-102 (heptadecan-9-yl 8-((2-hydroxyethyl)(6-oxo-6-(undecyloxy)hexyl)amino)octanoate), or DOPE (1,2-dioleoyl-sn-3-phosphoethanolamine), or DOTMA (N-(2,3-dioleyloxy)propyl)N,N,N-trimethylammonium chloride) or DOSPA (N-(1-(2,3-dioleyloxy)propyl)-N-(2-(sperminecarboxamido)ethyl)-N,N-dimethylammonium trifluoroacetate); (ii) a non-cationic helper lipid or phospholipid, such as a neutral lipid, such as DSPC (1,2-distearoyl-i77-glycero-3-phosphocholine) or an analogue or substitute thereof; (iii) sterols or other structural lipids, such as cholesterol; and (iv) PEG lipids, such as 1,2-dimyristoyl-sn-glycerol methoxypolyethylene glycol (PEG-DMG) The second fluid may contain at least one lipid selected from the group consisting of: Other lipids may also be suitable for inclusion in the second fluid. Further alternatives to PEG-lipids are polysarcosine, polyoxazoline, uncharged lipids such as pSar or pMeOx. However, PEG-lipid alternatives are not limited to those mentioned.

[0091] According to at least one embodiment, both the first fluid material and the second fluid material are colloidal suspensions, for example, ionic colloidal suspensions.

[0092] According to at least one embodiment, the first fluidic substance is or comprises a polymeric amphiphilic substance, or a polymeric lipophilic substance, or a polymeric hydrophilic substance; and The second fluid substance comprises an amphiphilic substance, or a polymeric amphiphilic substance, or a polymeric lipophilic substance, or a polymeric hydrophilic substance.

[0093] According to at least one embodiment, the first fluidic substance and / or the second fluidic substance is buffered. According to at least one embodiment, the first fluidic substance and / or the second fluidic substance is unbuffered.

[0094] According to at least one embodiment, one of the first and second fluid substances, or the mixture of fluid substances, is a pharmaceutical substance, such as a biopharmaceutical substance.

[0095] According to at least one embodiment, at least one or both of the first fluid substance and the second fluid substance are aqueous compositions, such as aqueous solutions or dispersions, or both the first fluid substance and the second fluid substance are aqueous compositions, such as aqueous solutions or dispersions.

[0096] According to at least one embodiment, at least one or both of the first fluid material and the second fluid material is a solution.

[0097] According to at least one embodiment, at least one or both of the first fluid material and the second fluid material is a dispersion.

[0098] According to at least one embodiment, the first fluid material is an aqueous composition, such as an aqueous solution or dispersion, and the second fluid material is an organic composition.

[0099] According to at least one embodiment, the organic composition is an organic solution or dispersion.

[0100] An organic composition can be defined as a composition that contains, for example, more than 1%, more than 10%, more than 25%, more than 50% organic solvent.

[0101] According to at least one embodiment, at least one or both of the first and second fluid substances are medical fluid substances.

[0102] According to at least one embodiment, the fluid material mixture is a colloidal suspension and / or includes particles, e.g., nanoparticles. The particles can be formed from one or more components of a first fluid material and one or more components of a second fluid material. The particles can be any nanoparticle, e.g., polymeric nanoparticles, or particles comprising lipids and polymers, e.g., lipid or liposome nanoparticles (LNPs), lipoplexes (LPXs), or polyplexes (PPXs). The nanoparticle composition can include nucleic acids, e.g., RNA (ribonucleic acid), such as mRNA (messenger ribonucleic acid), or DNA (deoxyribonucleic acid).

[0103] According to at least one embodiment, the nanoparticles can have a particle size (e.g., maximum diameter, minimum diameter, or average diameter) of 20 nm, 50 nm, 100 nm, 250 nm, 300 nm, 350 nm, 400 nm, 450 nm, 500 nm, 600 nm, 650 nm, 700 nm, or more. According to a final embodiment, the nanoparticles can have a particle size of 750 nm, 700 nm, 650 nm, 600 nm, 550 nm, 500 nm, 450 nm, 400 nm, 350 nm, 300 nm, 250 nm, 200 nm, 150 nm, 100 nm, 50 nm, or less. The nanoparticles can have a particle size between 20 nm and 1000 nm, e.g., between 250 nm and 750 nm.

[0104] According to at least one embodiment, the first fluid pathway is fluidly connected or fluidly connectable to a first reservoir containing a first fluidic substance such that a first fluidic substance can be driven from the first reservoir towards the mixing area via the first fluid pathway, and / or the second fluid pathway is fluidly connected or fluidly connectable to a second reservoir containing a second fluidic substance such that a second fluidic substance can be driven from the second reservoir towards the mixing area via the second fluid pathway.

[0105] According to at least one embodiment, the fluid pathway system is a closed system. In this context, the term "closed" refers to a system that is sealed from the environment between one or more system inlets and one or more system outlets. This ensures the sterility of the system. In a closed system, the fluid pathway system has an interior wall that defines the system from the outside at any location within the fluid pathway system.

[0106] According to at least one embodiment, the fluid path system may be pressure equalized via a sterile filter, i.e., allowing for a sterile inlet and / or outlet, e.g., via a sterile filter for pressure equalization.

[0107] According to at least one embodiment, the fluid pathway system is an uninterrupted system, which in this context may be understood as meaning that the elements through which the first fluid material, the second fluid material, and the fluid material mixture pass are physically connected to each other without any interruptions.

[0108] According to at least one embodiment, the fluid pathway system is an uninterrupted system. For example, the non-guiding flow region may not be physically connected to the directing region. However, an uninterrupted and / or closed system is preferred, for example, to maintain sterility within the fluid pathway system.

[0109] According to at least one embodiment, the fluid handling system comprises a reservoir region for collecting the fluid material mixture, the reservoir region being located downstream of the non-guiding flow region as viewed along the direction of flow of the fluid material mixture in the fluid handling system.

[0110] According to at least one embodiment, the fluid material mixture within the reservoir region forms a surface defining the reservoir region, e.g., on a side opposite the non-guiding flow region side, when viewed in a direction opposite the flow direction of the fluid material mixture into the reservoir region.

[0111] According to at least one embodiment, the fluid handling system is configured such that the fluid substance mixture, after moving through the non-guided flow region, flows into the reservoir region via the surface, for example in the form of fluid jets or fluid droplets impacting the surface.

[0112] According to at least one embodiment the fluid handling system comprises a reservoir region outlet in fluid communication with the reservoir region and provided for removing contents, eg a fluid substance mixture, from the reservoir region.

[0113] According to at least one embodiment the fluid material mixture in the reservoir region contacts an inner wall that laterally defines the fluid handling system.

[0114] The fluid substance mixture within the reservoir region may no longer exhibit its transition state, e.g., its intermediate state, such that contact of the fluid substance mixture with the inner wall of the reservoir region does not change (or at least does not substantially change) the physicochemical properties of the fluid substance mixture or its components (particles, e.g., nanoparticles, e.g., RNA such as mRNA, lipid or liposomal nanoparticles (LNPs), lipoplexes (LPXs), polyplexes (PPXs), etc.).

[0115] According to at least one embodiment, the fluid path system comprises a reservoir region.

[0116] According to at least one embodiment, the reservoir region is disposed within the container.

[0117] According to at least one embodiment, the reservoir region or container has a larger volume than the mixing region. According to at least one embodiment, the reservoir region or container has a smaller volume than the mixing region.

[0118] According to at least one embodiment, the container or reservoir region has a fill volume of 0.5 L, 1 L, 2 L, 3 L, 4 L, 5 L, 6 L, 7 L, 8 L, 9 L, 10 L, 15 L, 20 L, 25 L, 30 L, 35 L, 40 L, 45 L, 50 L, 100 L, 200 L, 300 L, 400 L, 500 L, 600 L, 700 L, 800 L, 900 L, 1000 L or more.

[0119] According to at least one embodiment, the container or reservoir region has a fill volume of less than or equal to 1000 L, 900 L, 800 L, 700 L, 600 L, 500 L, 400 L, 300 L, 200 L, 150 L, 100 L, 50 L, 45 L, 40 L, 35 L, 30 L, 25 L, 20 L, 15 L, 10 L, 5 L. The container or reservoir region may have a fill volume between 0.5 L and 1000 L, e.g., between 10 L and 500 L, e.g., 50 L.

[0120] According to at least one embodiment, the container, e.g., a bag, is collapsible and / or has flexible walls defining its interior, or the container, e.g., a flask, is non-collapsible and / or has rigid walls defining its interior.

[0121] According to at least one embodiment, at least a portion of the non-guided flow region or the entire non-guided flow region is within the vessel.

[0122] According to at least one embodiment the fluid handling system, eg the vessel, comprises a port, eg downstream of the non-guided flow region and / or within the vessel, for adding a further substance to the fluid substance mixture.

[0123] According to at least one embodiment, the fluid handling system is configured such that downstream of the non-guiding flow region the fluid material mixture is guided from the non-guiding flow region towards an outlet of the fluid handling system or fluid pathway system, for example so that the fluid material mixture can be continuously withdrawn from the fluid handling system via the outlet.

[0124] The guided discharge of the fluid material mixture from the fluid handling system may occur immediately downstream of the non-guided flow region, such that the fluid material mixture being discharged from the non-guided flow region is guided out. The guided discharge of the fluid material mixture from the fluid handling system may, however, also occur downstream of the reservoir region, from which the fluid material mixture may be guided out towards an outlet of the fluid handling system or fluid pathway system.

[0125] According to at least one embodiment, the fluid handling system comprises a mixture flow driver. The mixture flow driver may be a pump, for example one of those described above, or another type mentioned above for the first or second flow drivers. The mixture flow driver may be configured to move the fluidic material mixture from the reservoir region, for example towards an outlet of the fluid pathway system and / or the fluid handling system. Due to the non-guiding flow region, a flow driver that drives fluid into the non-guiding flow region may not be suitable for driving the fluidic material mixture out of the reservoir region. Thus, the mixture flow driver may improve the fluid handling system.

[0126] According to at least one embodiment, the fluid path system includes an increase in the diameter of the mixture fluid path of the fluid path system in the non-guided flow region to allow for non-guided flow of the fluid material mixture in the non-guided flow region.

[0127] According to at least one embodiment, the diameter of the mixture fluid path varies in the non-guiding flow region, and this diameter may be varied to facilitate preventing contact of the fluid material mixture with walls, such as the interior walls of the non-guiding flow region.

[0128] According to at least one embodiment, the diameter of the mixture fluid path increases in the non-guiding flow region away from the mixing region, e.g., at least in a portion of the mixture fluid path, and / or continuously (e.g., up to the reservoir region).

[0129] According to at least one embodiment, the diameter of the mixture fluid path decreases in the non-guided flow region away from the mixing region, for example, at least in a portion of the mixture fluid path, and / or continuously.

[0130] According to at least one embodiment the fluid handling system comprises at least one agitator for agitating the fluidic material, which may for example be a mixture of fluidic materials in a mixing region.

[0131] According to at least one embodiment, at least one agitator is arranged for agitating the fluid substance mixture, for example in the reservoir region.

[0132] According to at least one embodiment, at least one agitator is disposed within the contents to be agitated.

[0133] According to at least one embodiment, the at least one stirrer is a magnetic stirrer, such as a magnetic stir bar.

[0134] According to at least one embodiment, the mixing region has a first inlet for a first fluid material and a second inlet for a second fluid material, which may be adjacent to or coincident with the outlets of the first and second fluid paths, respectively.

[0135] According to at least one embodiment, the mixing region is formed by and / or within a mixing element connected to a first tube defining a first fluid path and / or a second tube defining a second fluid path.

[0136] According to at least one embodiment, the mixing element has an outlet directed into a non-directing flow region, optionally an outlet directed into a directing region, or an outlet that is part of a directing region.

[0137] According to at least one embodiment, the mixing element is a T-shaped element, a Y-shaped element, or an X-shaped element (e.g., an element having two first inlets or two second inlets for a first fluid material or a second fluid material, respectively, e.g., a first inlet for a first fluid material and two second inlets for a second fluid material, or a element having two first inlets for a first fluid material and one second inlet for a second fluid material). An X-shaped element may also have a first inlet for a first fluid material, a second inlet for a second fluid material, and a third inlet for a third fluid material. The mixing element may also have a ψ shape.

[0138] According to at least one embodiment, the mixing region is provided by a portion of a continuous tubular structure having further portions providing a first fluid path and a second fluid path, which may be fluidly separated from one another up to the mixing region.

[0139] According to at least one embodiment, the structural elements directing the first fluid, the second fluid, and / or the fluid substance mixture may be made of or comprise plastic or non-plastic materials. For example, the tubing for the first fluid path, the second fluid path, and / or the mixing region may be made of or comprise plastic, such as medical grade plastic and / or polypropylene or polyvinylidene fluoride (PVDF), or a non-plastic material, such as a medical grade material such as stainless steel. Further elements of the fluid handling system (e.g. non-directing flow regions or directing regions or mixing components) may also be made of or comprise these materials.

[0140] According to at least one embodiment the fluid handling system is configured to provide turbulent mixing of the first fluid material and the second fluid material in the mixing region.

[0141] In a further aspect, the present disclosure provides a method for producing a medicament for a medicament comprising: directing a first fluid material and a second fluid material in a fluid path system, such as those described above, to a mixing region to form a fluid material mixture, and preventing contact of the fluid material mixture with a wall (e.g., an interior wall) of the fluid path system for a predetermined time in a non-directing flow region along the flow direction of the fluid material mixture downstream of the mixing region. The present invention relates to a method for treating a fluid, comprising:

[0142] According to at least one embodiment, the method includes directing a third fluid material in the fluid path system to a mixing region to form the fluid material mixture.

[0143] According to at least one embodiment, the predetermined time is less than or equal to one of the following: 1 second, 950 milliseconds, 900 milliseconds, 850 milliseconds, 800 milliseconds, 750 milliseconds, 700 milliseconds, 650 milliseconds, 600 milliseconds, 550 milliseconds, 500 milliseconds, 450 milliseconds, 400 milliseconds.

[0144] According to at least one embodiment, the predetermined time is any one or more of the following: 1 millisecond, 5 milliseconds, 10 milliseconds, 20 milliseconds, 25 milliseconds, 50 milliseconds, 100 milliseconds, 150 milliseconds, 200 milliseconds, 300 milliseconds.

[0145] According to at least one embodiment, the first fluid material and the second fluid material are selected such that the fluid material mixture obtained by mixing the first fluid material and the second fluid material has an intermediate state, for example, during and / or immediately after mixing of the first fluid material and the second fluid material.

[0146] According to at least one embodiment, the intermediate state is a temporary state, e.g., a state that exists for less than a certain time, which may substantially correspond to or may be less than a predetermined time during which the fluid material mixture is prevented from contacting the walls (e.g., the interior walls) of the non-guiding flow region.

[0147] According to at least one embodiment, directing the first fluid material to the mixing region includes directing the first fluid material through a first fluid path of a fluid path system.

[0148] According to at least one embodiment, directing the second fluid material to the mixing region includes directing the second fluid material through a second fluid path of the fluid path system.

[0149] According to at least one embodiment, directing the third fluid material to the mixing region includes directing the third fluid material through a third fluid path of the fluid path system.

[0150] According to at least one embodiment, the method further includes directing the fluid material mixture through a directing region located downstream of the mixing region to direct the fluid material mixture toward a non-directing flow region.

[0151] According to at least one embodiment, the method further includes a step of directing the fluid material mixture within a fluid directing element of the fluid path system located downstream of the non-guiding flow region and / or receiving the fluid material mixture within a fluid holding element (e.g., a reservoir region) of the fluid path system located downstream of the non-guiding flow region.

[0152] According to at least one embodiment, the method further comprises the step of simultaneously directing the first fluid and the second fluid into the mixing region.

[0153] According to at least one embodiment, the method further includes driving the fluid flow of the first fluid with a first flow driver, such as a pump, e.g., a syringe pump, a peristaltic pump, a pressurized vessel, and / or a piston pump.

[0154] According to at least one embodiment, the method further includes driving the fluid flow of the second fluid by a second flow driver, such as a pump, e.g., a syringe pump, a peristaltic pump, a pressurized vessel, and / or a piston pump.

[0155] According to at least one embodiment, the method further includes driving the flow of the fluid material mixture downstream, or away from the non-guiding flow region, using a mixture flow driver, e.g., a pump such as a syringe pump, peristaltic pump, diaphragm pump, and / or piston pump, or a pressurized vessel. The fluid material mixture may be unaffected by the first and second flow drivers as it passes through the non-guiding flow region, or after it passes through the non-guiding flow region without contacting a wall (e.g., an interior wall). The mixture flow driver may enable movement of the fluid material mixture, for example, from the reservoir region toward an outlet, as it passes through the non-guiding flow region.

[0156] According to at least one embodiment, the method further comprises moving the fluid material mixture through a free fall or free flow region, which can be a non-guided flow region.

[0157] According to at least one embodiment the fluid handling system has a density of 1 g / cm 3 The mixing zone, directing zone, first inlet, second inlet, and / or outlet are configured to be operated at flow rates and / or have flow path diameters such that, for water having a viscosity of 1 cP and a temperature of 20°C, the relationship between flow rate and flow path diameter results in flow characterized by a calculated Reynolds number (Re) at the mixing zone, directing zone, first inlet, second inlet, and / or outlet of one of the following values ​​or less: 10,000, 7,500, 5,000, 4,000, 3,000, 2,900, 2,800, 2,700, 2,600, 2,500.

[0158] According to at least one embodiment the fluid handling system has a density of 1 g / cm 3The mixing zone, the directing zone, the first inlet, the second inlet, and / or the outlet are configured to be operated at flow rates and / or have flow channel diameters such that, for water having a viscosity of 1 cP and a temperature of 20°C, the relationship between flow rate and flow channel diameter results in flow characterized by a calculated Reynolds number (Re) of one or more of the following values ​​at the mixing zone, the directing zone, the first inlet, the second inlet, and / or the outlet: 500, 1000, 1100, 1200, 1300, 1400, 1500, 1700, 1800, 1900, 2000.

[0159] According to at least one embodiment the fluid handling system may be operated at flow rates of 100 mL / min, 200 mL / min, 300 mL / min, 400 mL / min, 500 mL / min, 600 mL / min, 700 mL / min, 800 mL / min, 900 mL / min, 1000 mL / min, 2 L / min, 5 L / min, 10 L / min, 20 L / min, 50 L / min, 80 L / min, 100 L / min or more.

[0160] According to at least one embodiment the fluid handling system may be operated at flow rates of up to 150 L / min, 100 L / min, 80 L / min, 50 L / min, 20 L / min, 10 L / min, 5 L / min, 2 L / min, 1100 mL / min, 1000 mL / min, 900 mL / min, 800 mL / min, 700 mL / min, 600 mL / min, 500 mL / min, 400 mL / min, 300 mL / min, 200 mL / min.

[0161] The fluid handling system may be operated at a flow rate of between 100 mL / min and 1100 mL / min, for example between 200 mL / min and 150 L / min, for example about 700 mL / min or 2 L / min or 5 L / min.

[0162] The operational flow rate value of the fluid handling system may relate to the flow rate of the fluid material mixture and / or the flow rate of the first fluid material and / or the second fluid material.

[0163] According to at least one embodiment, the method is carried out using the fluid path system of the present disclosure.

[0164] According to another aspect, the present disclosure relates to the use of a fluid handling system of the present disclosure for mixing a first fluid material with a second fluid material to provide a fluid material mixture.

[0165] According to another aspect, the present disclosure further relates to a fluid substance mixture obtainable or obtained by the fluid processing method or use described above or below.

[0166] According to another aspect, the present disclosure further relates to a nanoparticle composition, such as a lipid or liposomal nanoparticle (LNP) composition, such as a nucleic acid LNP, a lipoplex (LPX) composition, or a polyplex (PPX) composition, such as an RNA-LPX composition, obtainable or obtained by the method or use described above or below. [Brief explanation of the drawings]

[0167] [Figure 1a] FIG. 1a shows an exemplary blockage in the system. [Figure 1b] FIG. 1b shows a detailed view of an exemplary blockage in the system. [Figure 1c] FIG. 1c shows the size and polydispersity index values ​​of the fluid material mixture product. [Figure 1d] Figure 1d shows the time course of RNA content during a typical mixing process. [Figure 1e] FIG. 1e shows the amount of sub-visible particles at higher processing volumes for different tubing materials. [Figure 2a] Figures 2a and 2b show two fluid handling systems according to at least two different embodiments of the present disclosure. [Figure 2b] (the above) [Figure 3a] Figures 3a, 3b and 3c depict an exemplary embodiment of a fluid handling system. [Figure 3b] (the above) [Figure 3c] (the above) [Figure 4] Figure 4 shows a further exemplary embodiment of a fluid handling system. [Figure 5] FIG. 5 shows an exemplary embodiment of a method for processing a fluid. [Figure 6a] FIG. 6a shows particle size quantified by photon correlation spectroscopy (PCS) in the fluid material mixture product for different processing volumes. [Figure 6b] FIG. 6b shows the RNA content (mg / mL) in the fluid material mixture product for different processing volumes. [Figure 6c] FIG. 6c shows the amount of sub-visible particles in the fluid material mixture product with increasing processing volume. DETAILED DESCRIPTION OF THE INVENTION

[0168] DESCRIPTION OF ILLUSTRATIVE EMBODIMENTS Figure 1a shows a part of a fluid handling system where two fluids have already been mixed together to form a fluid substance mixture.

[0169] The diagram shows different stages during the run time of a system that is continuously mixing a first fluid material with a second fluid material to produce a fluid material mixture. The top tube shows the state of the system before the mixing process begins. The diagram shows an increasing visible amount of material DP deposited in tube 20 (only one tube 20 is marked in the diagram, with a fluid material mixture volume of 1750 mL after 150 seconds of run time).

[0170] A more detailed description of the different stages of the system is shown and explained in Figure 1b, where the stages at the start (run time 0 seconds, fluid material mixture volume 0 mL), after 1 minute (run time 60 seconds, fluid material mixture volume 700 mL), and after 3 minutes (run time 180 seconds, fluid material mixture volume 2 L) are shown.

[0171] Figure lb shows two tubes 20a, 20b in which two fluid materials are mixed together (the mixing region where mixing occurs is only partially visible on the left side of the figure and will be explained in more detail below). The two tubes represent different stages in the run-time of a system that continuously mixes a first fluid material with a second fluid material. The top tube (unlabeled) shows the state of the system before the mixing process begins.

[0172] As shown, in tube 20a, a visible amount of substance DP1 can be seen in the tube, i.e., tube 20a, at a fluid substance mixture volume of 700 ml after only 1 minute of run time (60 seconds). Thus, the fluid pathway conducting the fluid substance mixture may become clogged or blocked over time as the amount of deposits on the interior walls of the system increases. At a fluid substance mixture volume of 2 L after 3 minutes (180 seconds) of run time, there is a further increase in substance DP2 in tube, i.e., tube 20b.

[0173] Clogging can eventually cause complete blockage of the outlet tube 20, thereby interrupting the production of the fluid material mixture. This can occur particularly when the fluid material mixture resulting from mixing two fluids together is in a transition state, such as an intermediate state (colloquially referred to as a "viscous phase"), immediately after mixing the two fluids.

[0174] In some cases, only partial clogging occurs because the formed deposits are washed away. Once washed away, the deposits may remain in the final product, e.g., the fluid material mixture. This is disadvantageous because it changes the particle size distribution of the nanoparticles over time (e.g., a non-uniform distribution of particle sizes), resulting in a lower yield and a less uniform final product (e.g., the fluid material mixture) over time. In Figure 1B, the visible materials DP1 and DP2 have been washed away. The washed-away deposits change the particle size distribution in the fluid material mixture in a non-uniform manner. This effect is highly undesirable.

[0175] The fluid material mixture may include nanoparticles, such as lipid or liposomal nanoparticles (LNPs), e.g., nucleic acid LNPs, lipoplexes (LPXs), or polyplexes (PPXs). The nanoparticles may include RNA, e.g., mRNA, encapsulated in lipids and / or polymers. It has been found that fluid material mixtures suitable for forming nanoparticle compositions have a particular tendency to exhibit a transition or viscous phase.

[0176] Another problem encountered with the system can be, for example, the formation of particles with increased particle size and / or increased heterogeneity in the particle size of the formed nanoparticles, manifested, for example, by an increased polydispersity index (PDI) in the fluid material mixture. This can lead to reduced product homogeneity and even to products outside of established tolerance ranges (see, e.g., Figure 1c). For nucleic acid LNPs, e.g., RNA-LNPs, or nucleic acid lipoplexes, e.g., RNA-LPX, the PDI should be below a predetermined value (e.g., 0.4 or less, or 0.3 or less) and / or should not change significantly with increasing processing volume.

[0177] When the fluid material mixture contains RNA-LPX, the mixture produced in such a system may exhibit a decrease in RNA content, particularly a decrease in RNA concentration, with increasing processed volume. Therefore, several important product attributes may change significantly with increasing processed volume of the fluid material mixture. As can be seen from Figures 1c and 1d, in a typical mixing process using T-, Y-, or X-shaped mixing components with tubing at the inlet and tubing for the fluid material mixture at the component's outlet, for example, particle characteristics changed significantly with increasing processing volume. Notably, the materials of the components used, i.e., the tubing and components, did not significantly affect the important attributes (see, e.g., Figure 1e).

[0178] In one possible embodiment, the first fluid substance may comprise buffered RNA, more specifically 0.3 mg / mL BNT162b2 RNA, 18 mM HEPES and EDTA, pH 7 (NaOH), and the second fluid substance may comprise liposomes, more specifically L6 liposomes with an average particle size of about 550 nm in 0.6 mM DOTMA and 1.1 mM acetic acid.

[0179] However, it has been found that other fluid substances may also have an increased tendency to form deposits on the walls of the structural element through which the fluid substance mixture is conducted, for example immediately after the first and second fluid substances are mixed (see the Summary section of the specification).

[0180] Figure 2a shows an exemplary embodiment of a fluid handling system 100 of the present disclosure.

[0181] The fluid handling system 100 comprises a fluid pathway system, for example a closed fluid pathway system (e.g., sealed from the surrounding environment between the inlet and outlet of the fluid pathway system), comprising a first fluid pathway 202 that directs a first fluid substance F1 towards a mixing region 300 of the fluid pathway system and a second fluid pathway 204 that directs a second fluid substance F2 towards the mixing region 300.

[0182] The mixing region 300 is arranged in fluid communication with the first fluid path 202 and the second fluid path 204 such that the first fluid material F1 and the second fluid material F2 can mix in the mixing region 300 to form a fluid material mixture MX. The fluid handling system 100 may be configured to provide turbulent mixing of the first and second fluid materials in the mixing region 300.

[0183] The mixing area 300 comprises a first inlet 302 for a first fluid substance F1 and a second inlet 304 for a second fluid substance F2. The mixing area may be formed by a mixing component, the inlets and outlets of which may be connected to tubes for conducting the respective liquids or fluids.

[0184] The mixing element 306 (shown with dashed lines for clarity) may be connected to a first tube 202. The first tube 202 may define a first fluid pathway 202. The mixing element 306 may be connected to a second tube 204. The second tube 204 may define a second fluid pathway 204. The first tube 202 may be inserted into, for example, a first inlet 302 of a mixing region 300 of the mixing element 306. The second tube 204 may be inserted into, for example, a second inlet 302 of a mixing region 300 of the mixing element 306. The first and second fluid pathways may have the same diameter (e.g., minimum diameter, maximum diameter, or average diameter), for example, 4 cm or 5 cm.

[0185] The mixing region 300 may be provided by a portion of a continuous tubular structure (in which case a separate mixing component is not required). The tubular structure may include additional portions providing the first fluid path 202 and / or the second fluid path 204. The first fluid path 202 and the second fluid path 204 may be fluidly separated from each other. The first fluid path 202 and the second fluid path 204 may be fluidly separated from each other up to the mixing region 300.

[0186] The mixing element 306, in this embodiment, is substantially T-shaped (i.e., the element can be a T-mixer), as indicated by the dashed line in the figure. Other shapes for the mixing element are also possible, such as Y-shaped, X-shaped, or ψ-shaped. The mixing element 306 can be configured such that when the first tube 202 and the second tube 204 are connected (e.g., plugged) into the mixing element 306, the first flow direction and the second flow direction form an angle. This angle can be, for example, between 45° and 315°, such as 60°. This angle can also be different from 180°.

[0187] However, as in a T-mixer, the first and second fluids may impinge on each other in opposite flow directions to enhance mixing in the mixing region. The mixing element may have an outlet directed into the non-guiding flow region 400. In this embodiment, the outlet of the mixing element is part of the directing region 500 (see below).

[0188] The structure of the first fluid pathway 202, the second fluid pathway 204 (e.g., tubing) and / or the mixing region 300 (and / or the mixing component 306) may be made of or include a plastic, such as, for example, a medical grade plastic and / or polypropylene or polyvinylidene fluoride (PVDF), or a non-plastic material, such as, for example, a medical grade material, such as stainless steel.

[0189] The fluid handling system 100 further comprises a non-guiding flow region 400. The non-guiding flow region 400 is configured such that, while the fluid material mixture MX moves through the non-guiding flow region 400, contact of the fluid material mixture MX with internal walls 402, 404 (e.g., any internal walls) suitable for guiding the flow of the fluid material mixture MX along the flow direction AR1 of the fluid material mixture MX is prevented. In the illustrated embodiment, the non-guiding flow region 400 has an increased internal diameter (e.g., minimum diameter, maximum diameter, or average diameter) compared to elements adjacent to the non-guiding flow region in the upstream direction. Elements adjacent to the non-guiding flow region, for example, the outlet of the directing region, may have a diameter (e.g., minimum diameter, maximum diameter, or average diameter) that is at least half or less than half the internal diameter of the non-guiding flow region. The non-guiding flow region may have an internal diameter of, for example, 20 cm, while the diameter of the outlet of the directing region may be 0.64 cm.

[0190] The non-guiding flow region 400 extends a predetermined distance, for example, a predetermined distance. The non-guiding flow region 400 may extend a predetermined distance downstream of the mixing region 300. The predetermined distance may be the distance d1 shown in FIG. 2a. In this example, the distance d1 corresponds to the extension of the inner wall 402. The distance d1 may be, for example, between 5 cm and 565 cm, such as 165 cm, 68 cm, 35 cm, 25 cm, or 20 cm.

[0191] It has been found that reducing or preventing the possibility of the fluid substance mixture MX contacting the interior walls, for example, immediately or shortly after performing the mixing process, can be beneficial for, for example, but not limited to, the formation of RNA-LPX (see further below). Thus, providing a fluid handling system with such a non-guided flow region provides an improved system.

[0192] In the embodiment of Figure 2a, a fluid directing element 406 of the fluid handling system 100 is arranged downstream of the non-directing flow region 400 to direct the fluid material mixture MX. Alternatively, or in addition, a fluid retention element (not shown) of the fluid handling system 100 may be arranged downstream of the non-directing flow region 400 to receive the fluid material mixture MX.

[0193] As exemplarily shown in FIG. 2a, the first fluid path 202 and the second fluid path 204 may be arranged to allow the first fluid material F1 and the second fluid material F2 to move simultaneously through the mixing region.

[0194] The flow AR2 of the first fluid material F1 in the first fluid path and / or the flow AR3 of the second fluid material F2 in the second fluid path 204 may be driven by a first and / or a second flow driver, e.g., a pump, e.g., a diaphragm pump (see flow drivers 206 and 208), respectively. Optionally, a further flow driver 708 (e.g., a pump) may be disposed downstream of the non-guiding region 400 to drive the flow of the fluid material mixture MX after it has passed through the non-guiding region 400. Between the inlet of the non-guiding flow region and its outlet, there may be a region that is not completely filled with liquid or fluid material mixture. Therefore, the first and second flow drivers may not be sufficient to drive the flow of the liquid material mixture downstream of the non-guiding flow region.

[0195] As shown in Figure 2a, the fluid handling system 100 further comprises a directing region 500. The directing region may be located between the mixing region 300 and the non-guiding flow region 400, viewed along the flow direction AR1. The directing region 500 may be configured to determine, e.g. set, an inlet flow direction AR4 of the fluid material mixture MX. The inlet flow direction AR4 may be the flow direction in which the fluid material mixture MX flows into the non-guiding flow region 400.

[0196] The directing region 500 may be particularly advantageous when the fluid handling system 100 is arranged such that gravity causes the fluid material mixture to change flow direction after entering the non-guiding flow region 400. If the fluid material mixture flows vertically or along the force of gravity, as shown in Figure 2a, the directing region may be less advantageous, but may still have a positive directional effect on the flow into the non-guiding flow region 400; for example, the flow in the mixing region 300 may be more turbulent than in the non-guiding flow region 400.

[0197] In other cases where the flow direction of the non-guiding flow region may be changed by gravity, the directing region can define the inlet flow direction of the fluid material mixture MX into the mixing region 300, for example, the mixing region 300 is configured to or directly directs the flow of the fluid mixture into the non-guiding flow region 400 such that the flow does not contact any interior walls (see 402 and 404) as it passes through the non-guiding flow region 400. The directing region 500 can be approximately 2 cm long.

[0198] In the exemplary embodiment of Figure 2a, the inlet flow direction AR4 is parallel to the major axis of the unguided flow region and oriented along the force of gravity. Alternatively, the inlet flow direction AR4 may be at an angle to the major axis of the unguided flow region 400 and / or to gravity (see, e.g., arrow AR6 relative to AR7 in Figure 4).

[0199] As shown in FIG. 2a, the fluid path of the fluid path system directing the fluid substance mixture MX widens (as indicated by reference numerals 408a, 408b) along the flow direction away from the mixing region 300, for example, at the end of the directing region 400, when viewed along the flow direction from the mixing region 300 towards the non-directing flow region 400.

[0200] During the predetermined distance d1 of the non-guiding flow region 400, the fluid handling system 100 may comprise a free fall region 600 or free flow region 600 that allows the fluid substance mixture MX to move within the fluid handling system 100 without contacting the inner walls 402, 404 of the fluid handling system 100, for example the inner walls of the non-guiding flow region 400.

[0201] The free fall region 600 may be achieved by the shape of the non-guiding flow region 400 and, optionally, by the direction of the fluid material mixture MX received by the directing region 500 .

[0202] The fluid path system defines a first flow direction AR2 for the flow of a first fluid substance F1 from the first fluid path 202 through the first inlet into the mixing region 300. The fluid path system defines a second flow direction AR3 for the flow of a second fluid substance F2 from the second fluid path 204 through the second inlet into the mixing region 300. The first flow direction AR2 and the second flow direction AR3 may form an angle of, for example, 120°.

[0203] In this embodiment, the non-guiding flow region 400 can have an inlet region 410. The inlet region is the region of the non-guiding flow region where the fluid material mixture enters the non-guiding flow region. The mixing region 300 can additionally or alternatively include an outlet for the fluid material mixture. In this embodiment, the mixing region outlet is 2 mm wide (not shown).

[0204] In this particular embodiment, the inlet region 410 of the non-guiding flow region is adjacent to (or coincides with) the outlet of the directing region 500 .

[0205] In this example, the non-guiding flow region 400 may be 35 cm long. The non-guiding flow region 400 may be selected such that contact between the fluid material mixture MX and the inner walls 402, 404 of the non-guiding flow region 400 can be or is prevented for a predetermined period of time, for example about 5 milliseconds, during operation of the fluid handling system 100. The extent of the non-guiding flow region may be selected such that at a given flow rate there is sufficient time for the material mixture to adopt its steady state, or at least significantly reduce its tendency to form deposits on the inner walls.

[0206] The fluid handling system 100 has a density of 1 g / cm 3 The flow path may be further configured to be operated at a flow rate and / or have a flow path diameter (e.g., minimum, maximum, or average diameter) such that the relationship between flow rate and flow path diameter for water having a viscosity of 1 cP and a temperature of 20°C produces flow characterized by a calculated Reynolds number (Re) of 1100 at the mixing region 300, the directing region 500, the first inlet, the second inlet, and / or the outlet.

[0207] The first fluid substance F1 and the second fluid substance F2 may be selected such that the fluid substance mixture MX obtained by mixing the first fluid substance F1 and the second fluid substance F2 has an intermediate state, such as a temporary or transitional state, which may occur, for example, during and / or immediately after mixing the first fluid substance F1 and the second fluid substance F2.

[0208] The intermediate state may exist for less than a predetermined time. After the intermediate state, the fluid material mixture MX may assume a steady state. In the intermediate state, the fluid material mixture MX may be more prone to forming deposits on walls, e.g., interior walls defining the flow path, than in the steady state. An example of a tube clogging problem associated with this tendency to form deposits is shown in FIG. 1, which illustrates an example of a system clogging.

[0209] The flow handling system 100 is configured and / or operable such that in its intermediate state, the fluid material mixture MX flows only through the mixing region 300 and / or the non-guiding flow region 400 and / or optionally the directing region 500.

[0210] The first fluid material F1 and the second fluid material F2 can be selected to form a fluid material mixture MX containing colloids. The colloids can have an average particle size of 10 nm to 1000 nm, e.g., between 200 nm and 500 nm, e.g., about 400 nm, when mixed. For example, in the case of nucleic acid LPX, such as RNA-LPX, the particle size can depend on the size of the lipid-wrapped structure. Therefore, smaller or larger diameters or particle sizes can occur.

[0211] The first fluid substance F1 may contain RNA, for example, an RNA solution. The second fluid substance F2 may contain liposomes or lipoplexes. One or both of the fluid substances F1 and F2 may be buffered. When these substances are mixed, an RNA-LPX or an RNA-LNP may be formed.

[0212] The first and second fluid substances F1 and F2 can be, for example, ionic substances, such as cationic or anionic substances, or cationic and anionic substances. The first and / or second fluid substance mixture can be, for example, an ionizable substance. The first and second fluid substances F1 and F2 can be different from each other, for example, the first fluid substance F1 is an anionic substance and the second fluid substance F2 is a cationic substance.

[0213] The first fluid substance F1 may comprise a polymeric substance, for example a polymeric ionic substance. The first fluid substance F1 may comprise a nucleic acid, a peptide, or a protein.

[0214] The second fluid substance F2 may be a colloidal suspension, such as an ionic colloidal suspension, such as a cationic colloidal suspension. The second fluid substance F2 may comprise a hydrophilic and / or lipophilic substance, such as an amphiphilic substance. The second fluid substance F2 may comprise a lipid. The second fluid substance may comprise a cationic polymer.

[0215] The second fluid material F2 is (i) an ionizable lipid, preferably an ionizable cationic lipid, such as an ionizable cationic amino lipid, such as ALC-0315 ((4-hydroxybutyl)azanediyl)bis(hexane-6,1-diyl)bis(2-hexyldecanoate)), or SM-102 (heptadecan-9-yl 8-((2-hydroxyethyl)(6-oxo-6-(undecyloxy)hexyl)amino)octanoate), or DOPE (1,2-dioleoyl-sn-3-phosphoethanolamine), or DOTMA (N-(2,3-dioleyloxy)propyl)N,N,N-trimethylammonium chloride) or DOSPA (N-(1-(2,3-dioleyloxy)propyl)-N-(2-(sperminecarboxamido)ethyl)-N,N-dimethylammonium trifluoroacetate); (ii) a non-cationic helper lipid or phospholipid, such as a neutral lipid, such as DSPC (1,2-distearoyl-i77-glycero-3-phosphocholine) or an analogue or substitute thereof; (iii) sterols or other structural lipids, such as cholesterol; and (iv) PEG lipids, such as 1,2-dimyristoyl-sn glycerol methoxypolyethylene glycol (PEG-DMG) The second fluid may comprise at least one lipid selected from the group consisting of: Other lipids may also be suitable for inclusion in the second fluid. Further alternatives to PEG lipids may be (but are not limited to) polysarcosine, polyoxazoline, uncharged lipids such as pSar or pMeOx.

[0216] Both the first and second fluid substances may be colloidal suspensions, for example ionic colloidal suspensions. The first fluid substance may be or include a polymeric amphiphile, or a polymeric lipophile, or a polymeric hydrophile. The second fluid substance may include an amphiphile, or a polymeric amphiphile, or a polymeric lipophile, or a polymeric hydrophile.

[0217] Both the first fluid substance and the second fluid substance can be pharmaceutical substances, e.g., biopharmaceutical substances. At least one or both of the first fluid substance and the second fluid substance can be aqueous compositions, e.g., aqueous solutions or aqueous dispersions. At least one or both of the first fluid substance and the second fluid substance can be solutions. At least one or both of the first fluid substance and the second fluid substance can be dispersions. The first fluid substance can be an aqueous composition, e.g., an aqueous solution or aqueous dispersion, and the second fluid substance can be an organic composition, e.g., an organic solution or dispersion. The organic composition can contain more than 1%, 10%, 25%, or 50% organic solvent.

[0218] One or both of the first and second fluid substances may be medical fluid substances.

[0219] All of the above combinations of first fluid material F1 and second fluid material F2 may tend to exhibit an intermediate state (e.g., a viscous phase) when mixed together to form the fluid material mixture MX, and the advantages described for the systems of the present disclosure apply to all of these fluids.

[0220] Such an intermediate state, e.g., a sticky phase, can occur in all charged polymer / lipid mixtures. Layer-by-layer deposition at the onset of material deposition in the mixed region is experienced for virtually all mixtures of charged molecules. During the mixing phase, a sticky, colloidally unstable intermediate is formed, which continues until one of the two fluid materials is completely saturated with the other fluid material, e.g., the first or second fluid material, and the nanoparticles are stabilized / passivated.

[0221] For LNPs with an N / P ratio (e.g., the ratio of positively charged polymeric amine (N = nitrogen) groups to negatively charged nucleic acid phosphate (P) groups) greater than 1, the process may operate on a different timescale. This is because LNPs are likely formed from lipids in ethanol solution or lipid-rich micellar intermediate structures. While the properties of the liposomes used in the LPX process influence the particle size distribution, rearrangement of existing structures may trigger this intermediate instability.

[0222] In one possible example, the first fluid substance may comprise buffered RNA, more specifically, 0.3 mg / mL BNT162b2 RNA, 18 mM HEPES and EDTA, pH 7 (NaOH), and the second fluid substance may comprise liposomes, more specifically, L6 liposomes with an average particle size of approximately 550 nm, containing 0.6 mM DOTMA and 1.1 mM acetic acid.

[0223] 2a, the first fluid path 202 is fluidly connected or fluidly connectable to a first reservoir 602. The first reservoir 602 may contain a first fluidic substance F1. The first fluidic substance F1 may be driven from the first reservoir 602 towards the mixing region 300 via the first fluid path 202. The second fluid path 204 may be fluidly connected or fluidly connectable to a second reservoir 604. The second reservoir may contain a second fluidic substance F2, such that the second fluidic substance F2 may be driven from the second reservoir 604 towards the mixing region 300 via the second fluid path 204.

[0224] The fluid handling system 100 may further comprise a reservoir region 700, for example a container, for example a bag, for collecting the fluid substance mixture MX. The reservoir region may have a capacity of 10 L. The reservoir region 700 may be located downstream of the non-guiding flow region 400, as viewed along the flow direction AR1 of the fluid substance mixture MX in the fluid handling system 100. The fluid substance mixture MX in the reservoir region 700 forms a surface 702. The surface 702 may define the reservoir region 700 on the side facing the non-guiding flow region 400, as viewed, for example, in the opposite direction to the flow direction AR1 of the fluid substance mixture MX towards the reservoir region 700. After traveling through the non-guiding flow region 400, the fluid substance mixture MX may flow into the reservoir region 700. The fluid substance mixture MX may flow into the reservoir region 700 via the surface 702, for example in the form of fluid droplets 704 impacting the surface.

[0225] The fluid handling system 100 may further comprise a reservoir region outlet 706. The reservoir region outlet 706 may be in fluid communication with the reservoir region 700. The reservoir region outlet 706 may be provided for removing contents, for example fluid substance mixture MX, from the reservoir region 700.

[0226] A mixture flow driver 708 may be operably coupled to the reservoir region, for example, connected to the reservoir region outlet 706. The mixture flow driver 708 may be used to provide a flow of the fluid material mixture MX (e.g., extract) from the reservoir region 700.

[0227] The reservoir region 700 can be included in the fluid path system. The reservoir region can be directly connected to the non-guiding flow region 400. The reservoir region can be a region in the fluid path system that is located downstream of and immediately adjacent to the non-guiding flow region.

[0228] One or more additional fluid substances may be added to the mixture in a reservoir region, e.g., downstream of the non-guided flow region 400 of the vessel, and / or into the vessel 700 via a port (not explicitly shown).

[0229] From the reservoir region 700, a fluid material mixture MX may be continuously withdrawn, for example, from downstream of the non-guided flow region 400 via a flow driver 708.

[0230] The fluid handling system 100 may further comprise an agitator, for example a magnetic agitator. The agitator may be positioned within the contents to be stirred to agitate the fluidic substance. The agitator may for example be positioned within the reservoir region to agitate the fluidic substance mixture MX within the reservoir region (not shown).

[0231] Figure 2b shows a different exemplary embodiment of a fluid handling system 100. The fluid handling system 100 of Figure 2b is substantially similar to the fluid handling system 100 described in Figure 2a. Like reference numerals refer to like features. Only the differences between the fluid handling system 100 of Figure 2b and the fluid handling system 100 of Figure 2a will be described.

[0232] The fluid handling system 100 in the embodiment of Figure 2b is an example of an uninterrupted system. In particular, the non-guiding flow region 400 may be physically separated from the mixing region 300. The non-guiding flow region 400 may be physically separated from the directing region 500. The fluid material mixture MX flowing downstream from the directing region 500 free falls for a predetermined time and a predetermined distance, during which it does not contact the walls 402, 404 of the non-guiding flow region.

[0233] Figures 3a, 3b and 3c show further exemplary embodiments of the fluid handling system 100 of Figures 2a and 2b. The difference between the different embodiments of Figures 3a and 3b is the shape of the non-guiding flow region 400. The fluid handling system shown in Figure 3c instead comprises a differently shaped non-guiding flow region and a differently shaped mixing region 300 and / or directing region 500.

[0234] 3a and 3b, the diameter of the mixture fluid path changes in the non-guiding flow region 400. In FIG. 3a, in the non-guiding flow region 400, the diameter of at least a portion of the mixture fluid path increases in a direction away from the mixing region 300, e.g., in the fluid mixture flow direction AR4 exiting the directing region 500.

[0235] In FIG. 3 b , the diameter of the mixture fluid path instead decreases in the non-guiding flow region 400 in at least a portion of the mixture fluid path in a direction away from the mixing region 300 .

[0236] Figure 3c shows an exemplary embodiment of the fluid handling system 100 with two inlets for the second fluid material F2, e.g. two second inlets 304a, 304b, and one inlet for the first fluid material F1, e.g. one first inlet 302. The mixing region 300 may have an X-shape or a ψ-shape.

[0237] In an additional or alternative example, the inlet 304b may be a third inlet 304b for a third fluid substance in a third fluid pathway, for example a gas such as air.

[0238] The diameter of the mixture fluid path in the non-guiding flow region 400 first increases and then decreases in a direction away from the mixing region 300 in at least a portion of the mixture fluid path.

[0239] Figure 4 shows a further exemplary embodiment of the fluid handling system 100. In this example, the first fluid path 202, the second fluid path 204, the mixing region 300 and the directing region 500 are substantially tilted clockwise, for example by about 20 degrees, relative to the embodiment of the previous figure. The outlet of the directing region 500 may be tilted, for example by 20 degrees counterclockwise or clockwise. Each element may be independently positioned in a tilted or non-tilted position. The angle at which the elements are tilted may vary from element to element, or for only some elements.

[0240] In this embodiment, the inlet flow direction AR6 is angled relative to a major axis AR7 of the non-guiding flow region 400. The major axis may be oriented along the direction of gravity.

[0241] In such embodiments, i.e., embodiments in which the outlets of the mixing and / or directing regions do not face directly downward but are at a predetermined angle relative to the main downstream direction, the non-guiding flow region may be adapted to ensure non-guiding flow of the fluid material mixture, e.g., flow of the fluid material mixture for a predetermined period of time during which the fluid material mixture does not contact the inner walls 402 and 404 of the non-guiding flow region 400.

[0242] Once past the directing region, the redirection of the fluid material mixture in or just before the non-guiding flow region is achieved by gravity. The redirection of the fluid material mixture MX is shown in Figure 4 (indicated by the curved arrow and reference symbol MX).

[0243] In this embodiment, for example, the inner wall 402 of the non-guiding flow region can be positioned to ensure that the fluid material mixture MX exiting the directing region 500 does not contact the inner wall 402 for a predetermined time and / or a predetermined distance d2. The inner wall 402 can be configured to have a concave shape, as in the example of Figure 4 (when viewed from the inside). The distance d2 can correspond to the distance d1 in Figure 2a.

[0244] The distance d2 can be between 5 cm and 565 cm, for example 165 cm, 68 cm, 35 cm, 25 cm, or 20 cm.

[0245] Figure 5 shows a schematic diagram of an exemplary embodiment of a method for processing a fluid. Features of the method may be indicated with the same reference numerals as used in the description of the fluid handling system. However, the method is not limited to use with the fluid handling system 100 of the previous figure.

[0246] In a first step S1 of the method, a first fluid substance F1 and a second fluid substance F2 in a fluid pathway system are directed to a mixing region 300 to form a fluid substance mixture MX. In particular, directing the first fluid substance F1 to the mixing region 300 may include directing the first fluid substance F1 through a first fluid path of the fluid pathway system. Directing the second fluid substance F2 to the mixing region 300 may include directing the second fluid substance F2 through a second fluid path of the fluid pathway system.

[0247] The first fluid material F1 and the second fluid material F2 may be simultaneously introduced into the mixing region 300. For example, fluid flow of the first fluid material F1 and / or the second fluid material F2 towards the mixing region 300 may be achieved via a first flow driver and / or a second flow driver, respectively.

[0248] The first flow driver and / or the second flow driver can be, for example, a peristaltic pump. Alternatively, the first flow driver can be different from the second flow driver. For example, the first flow driver can be a syringe pump and the second flow driver can be a diaphragm pump, or vice versa.

[0249] The first fluid substance F1 and the second fluid substance F2 may be selected such that the fluid substance mixture MX obtained by mixing the first fluid substance F1 and the second fluid substance F2 has an intermediate state. The intermediate state may occur during and / or immediately after mixing the first fluid substance F1 and the second fluid substance F2. The intermediate state of the fluid substance mixture MX may simply be a temporary state.

[0250] The first fluid material F1 and the second fluid material F2 may be directed through the mixing region 300 for, for example, 40 milliseconds to form a fluid material mixture MX.

[0251] In an optional step not shown, the method includes directing a third fluid material in the fluid pathway system to a mixing region to form a fluid material mixture. Directing the third fluid material to the mixing region may include directing the third fluid material through a third fluid pathway of the fluid pathway system.

[0252] In a second step S2 of the exemplary method, contact between the fluid material mixture MX and the walls 402, 404 of the fluid path system is prevented for a predetermined time, which may occur downstream of the mixing region 300 in a non-guiding flow region 400 along the flow direction AR2 of the fluid material mixture Mx.

[0253] The fluid material mixture MX may have the intermediate state for less than a predetermined time, for example, only a predetermined time during which contact between the fluid material mixture MX and the walls 402, 404 of the fluid path system is prevented.

[0254] The method may further include directing the fluid material mixture MX through a free fall or free flow region, which may be, for example, a non-guiding flow region 300 or within a non-guiding flow region 300.

[0255] Prior to the second step S2, the fluid material mixture MX may be guided through a directing region 500 located downstream of the mixing region 300. By directing the fluid material mixture MX through the directing region 500, the fluid material mixture MX may be directed towards the non-guiding flow region 300.

[0256] The exemplary method may further include directing the fluid material mixture MX within a fluid directing element of the fluid path system located downstream of the non-directing flow region 300. Additionally or alternatively, the fluid material mixture MX may be received within a fluid retention element 700 of the fluid path system located downstream of the non-directing flow region 300.

[0257] Directing the fluid substance mixture MX within the fluid directing element of the fluid path system located downstream of the non-directing flow region 300 can be achieved, for example, by another mixture flow driver, for example a pump, for example a piston pump.

[0258] The fluid handling system 100 has a density of 1 g / cm 3 For water having a viscosity of 1 cP and a temperature of 20°C, the flow path may be configured to operate at a flow rate and / or have a flow path diameter such that the relationship between the flow rate and the flow path diameter results in a flow characterized by a calculated Reynolds number (Re) of 1100 at the mixing region 300, the directing region 500, the first inlet of the first fluid path, the second inlet of the second fluid path, and / or the outlet of the mixing region.

[0259] The exemplary methods described can be implemented using the fluid path system of any one of the above embodiments.

[0260] The fluid handling system may for example be used to mix a first fluid material F1 with a second fluid material F2 to obtain a fluid material mixture MX.

[0261] Figures 6a-6c illustrate the beneficial effect of the fluid handling system of the present disclosure on a provided fluid material mixture product.

[0262] The graph in Figure 6a demonstrates that the size of particles (as quantified in nm by Photon Correlation Spectroscopy (PCS)) in a fluid material mixture processed with a fluid handling system of any embodiment of the present disclosure, and optionally processed according to a method of any embodiment of the present disclosure, remains constant even as the processing volume increases. The "No Tube T" in the legend indicates that a free fall region was provided, e.g., a fluid handling system of the present disclosure equipped with a free fall region was used.

[0263] As can be seen, using the fluid handling system of the present disclosure, a consistent particle size (eg, average particle size) of about 400 nm can be achieved.

[0264] The graph in Figure 6b shows that when the fluid substance mixture contains RNA, the RNA content, ie, RNA concentration (mg / mL), remains essentially constant with increasing treatment volume.

[0265] These results suggest that by using the fluid handling system of the present disclosure, a consistent product quality of the fluid material mixture can be achieved even as the processing volume varies.

[0266] Figure 6c shows the amount of subvisible particles in the fluid material mixture product produced at different stages (e.g., F01-F20) at a pump speed of 200 mL / min (e.g., the processing capacity of the first and second fluid paths is 100 mL / min, respectively). As shown, the amount of subvisible particles (by-products) in the micrometer size range remains stable over time and is significantly lower than that of conventional processes (e.g., syringe pumps) marked with C1, C2, and C3.

[0267] Significant improvements compared to solutions without non-guided flow regions (see Figures 1a-1e) are immediately apparent. In particular, the number of by-products (e.g., subvisible particles (SVPs)) is reduced compared to conventional approaches. Furthermore, the number of SVPs does not increase over time, a phenomenon evident in conventional methods.

[0268] Further experimental results also showed that even when the volume ratio of the first fluid substance, e.g., RNA, to the second fluid substance, e.g., liposomes, was varied by up to 25%, there were no quality-related changes or trends indicating a significant decrease in the quality of the fluid substance mixture product, e.g., with respect to subvisible particles (SVPs).

[0269] It should be noted that features disclosed in the summary section of the specification also apply to the description of exemplary embodiments, even if they are not explicitly reiterated.

[0270] Without limiting the disclosure, a number of embodiments or clauses of the disclosure are described below for illustrative purposes, and although these clauses are not claims, they may be the subject of claims.

[0271] Section 1: 1. A fluid pathway system comprising: a first fluid path for directing a first fluid substance toward a mixing region of the fluid path system; a second fluid path for directing a second fluid material toward the mixing region; a mixing region arranged in fluid communication with the first fluid path and the second fluid path such that the first fluid material and the second fluid material can mix in the mixing region to form a fluid material mixture, A fluid handling system comprising a non-guiding flow region, the non-guiding flow region being capable of or configured to prevent contact of the fluid material mixture with an inner wall suitable for guiding the flow of the fluid material mixture along a flow direction of the fluid material mixture while the fluid material mixture moves through the non-guiding flow region, and the non-guiding flow region extending for a predetermined distance downstream of the mixing region, e.g. extending for only a predetermined distance. Clause 2: A fluid handling system according to clause 1, wherein a fluid directing or fluid retaining element of the fluid handling system is positioned downstream of the non-directing flow region to receive and / or direct the fluid material mixture. Clause 3: A fluid handling system according to any one of the preceding clauses, wherein the fluid handling system is configured to allow the first fluid material and the second fluid material to move simultaneously to the mixing region. Clause 4: A fluid handling system according to any one of the preceding clauses, wherein the diameter (e.g. minimum diameter, maximum diameter or average diameter) of the first fluid path and / or the diameter (e.g. minimum diameter, maximum diameter or average diameter) of the second fluid path is between 0.5 mm and 55 mm. Clause 5: A fluid handling system according to any one of the preceding clauses, wherein the fluid flow of the first fluid substance along the first fluid path is driveable or driven by a first flow driver, for example a pump such as a syringe pump, a peristaltic pump, a diaphragm pump and / or a piston pump, or a pressurised vessel. Clause 6: A fluid handling system according to any one of the preceding clauses, wherein the fluid flow of the second fluid substance along the second fluid path is driveable or driven by a second flow driver, for example a pump such as a syringe pump, a peristaltic pump, a diaphragm pump and / or a piston pump, or a pressurised vessel. Clause 7: A fluid handling system according to any one of the preceding clauses, wherein the fluid flow of the fluid material mixture downstream of the non-guiding flow region can be or is driven by a mixture flow driver, for example a pump such as a syringe pump, peristaltic pump, diaphragm pump and / or piston pump, or a pressurized vessel. Clause 8: A fluid handling system according to any one of the preceding clauses, wherein the fluid pathway system comprises a directing region positioned between the mixing region and the non-guiding flow region, viewed along the flow direction of the fluid material mixture, the directing region being configured to determine an inlet flow direction of the fluid material mixture through which the fluid material mixture enters the non-guiding flow region. Clause 9: A fluid handling system according to clause 8, wherein the orientation region has a length of less than or equal to one of the following values: 5cm, 4cm, 3.5cm, 3cm, 2.5cm, 2cm, 1.5cm, 1cm, 0.5cm, 0.4cm, 0.3cm, 0.2cm. Clause 10: A fluid handling system according to clause 8 or clause 9, wherein the directing region has a length of one or more of the following values: 0.05cm, 0.2cm, 0.5cm, 1cm, 1.5cm, 2cm. Clause 11: A fluid handling system according to any one of clauses 8 to 10, wherein the inlet flow direction is parallel to the major axis of the non-guiding flow region. Clause 12: A fluid handling system according to any one of clauses 8 to 10, wherein the inlet flow direction is inclined relative to a major axis of the non-guided flow region. Clause 13: A fluid handling system as described in any one of clauses 8 to 12, wherein the fluid path of the fluid path system for guiding the fluid substance mixture widens along the flow direction away from the mixing region, for example at the end of the directing region, when viewed along the flow direction from the mixing region towards the non-guiding flow region. Clause 14: A fluid handling system according to any one of the preceding clauses, having a free fall or free flow region which allows the fluid material mixture to move within the fluid handling system without contacting an inner wall of the fluid handling system, for example the inner wall closest to the fluid material mixture, for a predetermined distance, e.g. due to an interruption of the fluid path system in a non-guiding flow region and / or due to a mixture fluid path of the fluid path system being configured with an appropriate width in the non-guiding flow region. Clause 15: A fluid handling system according to any one of the preceding clauses, wherein the fluid pathway system defines a first flow direction for the flow of a first fluid material from the first fluid pathway through the first inlet into the mixing region, and wherein the fluid pathway system defines a second flow direction for the flow of a second fluid material from the second fluid pathway through the second inlet into the mixing region, the first flow direction and the second flow direction forming an angle, the angle being in the range between 45° and 315°, for example in the range between 60° and 300°, for example between 120° and 270°, or about 180°. Clause 16: A fluid handling system according to any one of the preceding clauses, wherein the mixing region has an outlet for the fluid substance mixture and / or the non-guiding flow region comprises an inlet region. Clause 17: A fluid handling system according to clause 16, wherein the internal diameter (e.g. minimum, maximum or average diameter) of the outlet or inlet region is between 0.5 mm and 6 cm, for example between 1 mm and 5.2 cm. Clause 18: A fluid handling system as claimed in clause 16 or 17, with an additional reference to clause 8 or any clause subordinate to clause 8, wherein the inlet region of the non-guiding flow region is adjacent to or coincident with the outlet of the directing region. Clause 19: A fluid handling system according to any one of the preceding clauses, wherein the predetermined distance is one or more of the following values: 5cm, 6cm, 7cm, 8cm, 9cm, 10cm, 11cm, 12cm, 13cm, 20cm, 35cm, 50cm, 80cm, 100cm, 200cm. Clause 20: A fluid handling system according to any one of the preceding clauses, wherein the predetermined distance is less than or equal to one of the following values: 565cm, 400cm, 300cm, 200cm, 165cm, 68cm, 35cm, 13cm. Clause 21: A fluid handling system according to any one of the preceding clauses, wherein the predetermined distance is selected such that contact of the fluid substance mixture with the inner wall is prevented or prevented for a predetermined period of time, for example during operation of the fluid handling system. Item 22: A fluid handling system according to item 21, wherein the predetermined time is one or less of the following times: 1 second, 950 milliseconds, 900 milliseconds, 850 milliseconds, 800 milliseconds, 750 milliseconds, 700 milliseconds, 650 milliseconds, 600 milliseconds, 550 milliseconds, 500 milliseconds, 450 milliseconds, 400 milliseconds. Clause 23: A fluid handling system according to clause 21 or 22, wherein the predetermined time is one or more of the following: 1 millisecond, 5 milliseconds, 10 milliseconds, 20 milliseconds, 25 milliseconds, 50 milliseconds, 100 milliseconds, 150 milliseconds, 200 milliseconds, 300 milliseconds. Item 24: The fluid handling system must be 3 1400, 1500, 1700, 1800, 1900, 2000, 2100, 2200, 2300, 2400, 2500, 2600, 2700, 2800, 2900, 3000, 3100, 3200, 3300, 3400, 3500, 3600, 3700, 3800, 3900, 4000, 4100, 4200, 4300, 4400, 4500, 4600, 4700, 4800, 4900, 5000, 5100, 5200, 5300, 5400, 5500, 5600, 5700, 5800, 5900, 6100, 6200, 6300, 6400, 6500, 6600, 6700, 6800, 6900, 7000, 7100, 7200, 7300, 7400, 7500, 7600, 7700, 7800, 7900, 8000, 8100, 8200, 8300, 8400, 8500, 8600, 8700, 8800, 8900, 9000, 9100, 9200, 9300, 9400, 9500, 9600, 9700, 9800, 9900, 1000, Clause 25: The fluid handling system must be3 2900, 2800, 2700, 2600, 2500, 3000, 3100, 3200, 3300, 3400, 3500, 3600, 3700, 3800, 4000, 4100, 4200, 4300, 4400, 4500, 4600, 4700, 4800, 4900, 5000, 5100, 5200, 5300, 5400, 5500, 5600, 5700, 5800, 5900, 6000, 6100, 6200, 6300, 6400, 6500, 6600, 6700, 6800, 6900, 7000, 7100, 7200, 7300, 7400, 7500, 7600, 7700, 7800, 7900, 8000, 8100, 8200, 8300, 8400, 8500, 8600, 8700, 8800, 8900, 9000, 9100, 9200, 9300, 9400, 9500, 9600, 9700, 9800, 9900, 10000, 10100, 10200, 10300, 10400, 10500, 10600, 10700, 10800, 109 Clause 26: A fluid handling system according to clause 24 or 25, wherein the fluid handling system is capable of handling or providing a fluid flow, for example the fluid flow in the mixing region, directing region, first inlet, second inlet and / or outlet has a Reynolds number (Re) of between 500 and 10,000, for example between 500 and 3,000, for example between 1,700 and 2,500. Clause 27: A fluid handling system according to any one of the preceding clauses, wherein the first fluid substance and the second fluid substance are selected such that the fluid substance mixture resulting from mixing the first fluid substance with the second fluid substance has an intermediate state, for example during and / or immediately after mixing of the first fluid substance with the second fluid substance. Clause 28: A fluid handling system according to clause 27, wherein the intermediate state is a temporary state, for example a state that exists for less than a predetermined time. Clause 29: A fluid handling system according to clause 27 or 28, wherein the fluid substance mixture attains a steady state after an intermediate state. Clause 30: A fluid handling system as described in any one of clauses 27 to 29, wherein the fluid substance mixture has a higher tendency in its intermediate state to form deposits on walls, for example internal walls defining a fluid path, than in the stable state. Clause 31: A fluid handling system according to any one of clauses 27 to 30, wherein the fluid handling system is configured to cause the fluid substance mixture, in its intermediate state, to flow through a non-guided flow region. Clause 32: A fluid handling system according to any one of clauses 27 to 31, wherein the fluid handling system is configured and / or operable so that the fluid substance mixture, in its intermediate state, flows only through the mixing region and / or the non-guiding flow region and / or optionally the directing region. Clause 33: A fluid handling system according to any one of the preceding clauses, wherein the first fluid substance and the second fluid substance are selected to form a fluid substance mixture comprising a colloid, for example having an average colloidal particle size of 10 nm or more and / or 1000 nm or less. Clause 34: A fluid handling system according to any one of the preceding clauses, wherein the first fluid substance comprises an ionic and / or ionisable substance. Clause 35: A fluid handling system according to any one of the preceding clauses, wherein the second fluid substance comprises an ionic and / or ionisable substance. Clause 36: A fluid handling system according to clause 34 or clause 35, wherein the ionic and / or ionisable substance is a cationic or anionic substance, or a cationic and anionic substance, for example a zwitterionic substance, and / or a cationic or anionic ionisable substance, or a cationic and anionic ionisable substance, for example a zwitterionic ionisable substance. Clause 37: A fluid handling system according to any one of clauses 34 to 36, wherein the ionic substance of the first fluid substance is an anionic substance and the ionic substance of the second fluid substance is a cationic substance. Clause 38: A fluid handling system according to any one of clauses 34 to 37, wherein the first fluid substance comprises a polymeric substance, for example a polymeric ionic substance. Clause 39: A fluid handling system according to any one of clauses 34 to 38, wherein the first fluid substance comprises a nucleic acid, a peptide or a protein. Clause 40: A fluid handling system according to any one of clauses 34 to 39, wherein the first fluid substance comprises RNA, optionally the first fluid substance is an RNA solution such as mRNA. Clause 41: A fluid handling system according to any one of the preceding clauses, wherein the second fluid substance is a colloidal suspension, such as an ionic colloidal suspension, such as a cationic colloidal suspension. Clause 42: A fluid handling system according to any one of the preceding clauses, wherein the second fluid substance comprises a hydrophilic and / or lipophilic substance, such as an amphiphilic substance. Clause 43: A fluid handling system according to any one of the preceding clauses, wherein the second fluid substance comprises at least one lipid. Clause 44: A fluid handling system according to any one of the preceding clauses, wherein the second fluid substance comprises a liposome. Clause 45: A fluid handling system according to any one of the preceding clauses, wherein the second fluid substance comprises a cationic polymer. Clause 46: A fluid handling system according to any one of clauses 1 to 45, wherein the first fluid substance and the second fluid substance are both colloidal suspensions, for example ionic colloidal suspensions. Item 47: The first fluid substance is or comprises a polymeric amphiphilic substance, a polymeric lipophilic substance, or a polymeric hydrophilic substance; 10. The fluid handling system of any one of the preceding clauses, wherein the second fluidic substance comprises an amphiphilic substance or a polymeric amphiphilic substance or a polymeric lipophilic substance or a polymeric hydrophilic substance. Clause 48: A fluid handling system according to any one of the preceding clauses, wherein the first fluid substance and / or the second fluid substance is buffered. Clause 49: A fluid handling system according to any one of the preceding clauses, wherein one of the first and second fluid substances or the mixture of fluid substances is a biopharmaceutical substance. Clause 50: A fluid handling system according to any one of the preceding clauses, wherein at least one or both of the first fluid substance and the second fluid substance are aqueous compositions, such as aqueous solutions or aqueous dispersions, or both the first fluid substance and the second fluid substance are aqueous compositions, such as aqueous solutions or aqueous dispersions. Clause 51: A fluid handling system according to any one of the preceding clauses, wherein at least one or both of the first fluid substance and the second fluid substance is a solution. Clause 52: A fluid handling system according to any one of the preceding clauses, wherein at least one or both of the first fluid substance and the second fluid substance is a dispersion. Clause 53: A fluid handling system according to any one of the preceding clauses, wherein the first fluid substance is an aqueous composition, such as an aqueous solution or dispersion, and the second fluid substance is an organic composition. Item 54: A fluid handling system according to item 53, wherein the organic composition is an organic solution or dispersion. Clause 55: A fluid handling system according to any one of the preceding clauses, wherein one or both of the first fluid substance and the second fluid substance is a medical fluid substance. Clause 56: A fluid handling system according to any one of the preceding clauses, wherein the fluid substance mixture is a colloidal suspension comprising particles, e.g. nanoparticles, formed from one or more components of a first fluid substance and one or more components of a second fluid substance, and optionally the nanoparticles are nanoparticle compositions, e.g. polymeric nanoparticles, or particles comprising lipids and polymers, e.g. lipid or liposomal nanoparticles (LNPs), lipoplexes (LPXs), polyplexes (PPXs). Clause 57: A fluid handling system according to any one of the preceding clauses, wherein the first fluid pathway is fluidly connected to or fluidly connectable to a first reservoir containing a first fluidic substance such that the first fluidic substance can be driven from the first reservoir towards the mixing area via the first fluid pathway, and / or the second fluid pathway is fluidly connected to or fluidly connectable to a second reservoir containing a second fluidic substance such that the second fluidic substance can be driven from the second reservoir towards the mixing area via the second fluid pathway. Clause 58: A fluid handling system according to any one of the preceding clauses, wherein the fluid path system is a closed and / or uninterrupted system. Clause 59: A fluid handling system according to any one of the preceding clauses, wherein the fluid handling system comprises a reservoir region for collecting the fluid material mixture, the reservoir region being positioned downstream of the non-inductive flow region as viewed along the flow direction of the fluid material mixture within the fluid handling system. Clause 60: A fluid handling system as described in clause 59, wherein the fluid material mixture in the reservoir region forms a surface defining the reservoir region on the side facing the non-inductive flow region, for example when viewed in a direction opposite to the flow direction of the fluid material mixture towards the reservoir region. Clause 61: A fluid handling system as described in clause 60, wherein the fluid handling system is configured such that after the fluid substance mixture has travelled through the non-guided flow region it flows into the reservoir region via the surface, for example in the form of a fluid jet or fluid droplets impacting the surface. Clause 62: A fluid handling system as described in any one of clauses 59 to 61, wherein the fluid handling system comprises a reservoir region outlet in fluid communication with the reservoir region and provided for removing contents, e.g. a fluid substance mixture, from the reservoir region. Clause 63: A fluid handling system according to any one of clauses 59 to 62, wherein the fluid substance mixture in the reservoir region contacts an inner wall that laterally defines the fluid handling system. Clause 64: A fluid handling system according to any one of clauses 59 to 63, wherein the fluid pathway system comprises a reservoir region. Clause 65: A fluid handling system according to any one of clauses 59 to 64, wherein the reservoir region is located within a container. Clause 66: A fluid handling system according to any one of clauses 59 to 65, wherein the reservoir region or container has a larger volume than the mixing region. Clause 67: A fluid handling system according to any one of clauses 59 to 66, wherein the reservoir region or container has a smaller volume than the mixing region. Item 68: A fluid handling system according to any one of items 66 to 67, wherein the container has a fill volume of 0.5L, 1L, 2L, 3L, 4L, 5L, 6L, 7L, 8L, 9L, 10L, 15L, 20L, 25L, 30L, 35L, 40L, 45L, 50L, 100L, 200L, 300L, 400L, 500L, 600L, 700L, 800L, 900L, 1000L or more. Item 69: A fluid handling system according to any one of items 66 to 68, wherein the container has a fill volume of 1000L, 900L, 800L, 700L, 600L, 500L, 400L, 300L, 200L, 150L, ​​100L, 50L, 45L, 40L, 35L, 30L, 25L, 20L, 15L, 10L or 5L or less. Clause 70: A fluid handling system according to any one of clauses 65 to 69, wherein the container, e.g. a bag, is collapsible and / or has flexible walls defining its interior, or the container, e.g. a flask, is non-collapsible and / or has rigid walls defining its interior. Clause 71: A fluid handling system according to any one of clauses 65 to 70, wherein at least part of the non-guided flow region or the whole of the non-guided flow region is within a container. Item 72: A fluid handling system according to any one of items 65 to 71, wherein the fluid handling system, for example a container, comprises a port, for example downstream of the non-guided flow region and / or within the container, for adding further substances to the fluid substance mixture. Clause 73: A fluid handling system according to any one of the preceding clauses, wherein the fluid handling system is configured such that the fluid material mixture is guided downstream of the non-guiding flow region from the non-guiding flow region towards an outlet of the fluid handling system or fluid pathway system, for example to enable continuous withdrawal of the fluid material mixture from the fluid handling system via the outlet. Clause 74: A fluid handling system as described in any one of the preceding clauses, wherein the fluid path system has an increased diameter of the mixture fluid path of the fluid path system in the non-guided flow region, thereby allowing non-guided flow of the fluid substance mixture in the non-guided flow region. Clause 75: A fluid handling system according to clause 74, wherein the diameter of the mixture fluid path varies in the non-guided flow region. Clause 76: A fluid handling system as described in clause 74 or clause 75, wherein the diameter of the mixture fluid path increases in the non-guiding flow region in a direction away from the mixing region, for example in at least part of the mixture fluid path and / or continuously. Clause 77: A fluid handling system as described in any one of clauses 74 to 76, wherein the diameter of the mixture fluid path decreases in the non-inductive flow region in a direction away from the mixing region, for example in at least part of the mixture fluid path and / or continuously. Clause 78: A fluid handling system according to any one of the preceding clauses, comprising an agitator for agitating the fluid substance. Clause 79: A fluid handling system according to clause 78, wherein an agitator is arranged, for example in the reservoir region, for agitating the fluid substance mixture. Clause 80: A fluid handling system according to clause 78 or 79, wherein the agitator is positioned within the contents to be agitated. Item 81: A fluid handling system according to any one of items 78 to 80, wherein the agitator is a magnetic agitator, such as a magnetic stir bar. Clause 82: A fluid handling system according to any one of the preceding clauses, wherein the mixing region has a first inlet for a first fluid material and a second inlet for a second fluid material. Clause 83: A fluid handling system according to any one of the preceding clauses, wherein the mixing region is formed by a mixing component connected to a first tube defining a first fluid path and / or a second tube defining a second fluid path. Clause 84: A fluid handling system according to clause 74, wherein the mixing component has an outlet directed towards the non-directing flow region, optionally directed towards the directing region or being part of the directing region. Item 85: A fluid handling system according to item 83 or 84, wherein the mixing element is a T-shaped element, a Y-shaped element, an X-shaped element or a ψ-shaped element. Clause 86: A fluid handling system according to any one of the preceding clauses, wherein the mixing region is provided by a portion of a continuous tube structure, the tube structure having a further portion providing a first fluid path and a second fluid path, the first fluid path and the second fluid path being fluidly separated from each other up to the mixing region. Clause 87: A fluid handling system according to any one of the preceding clauses, wherein the tubing structures for the first fluid path, the second fluid path and / or the mixing region are made of or include plastic, for example medical grade plastic and / or polypropylene or polyvinylidene fluoride (PVDF), or a non-plastic material, for example a medical grade material such as stainless steel. Clause 88: A fluid handling system according to any one of the preceding clauses, configured to provide turbulent mixing of the first fluid material and the second fluid material in the mixing region. Section 89: A method for treating a fluid, comprising: directing a first fluid material and a second fluid material in the fluid path system to a mixing region to form a fluid material mixture; preventing contact between the fluid material mixture and a wall of the fluid path system in a non-guiding flow region along the flow direction of the fluid material mixture downstream of the mixing region for a predetermined time; A method comprising: Clause 90: The method for processing a fluid according to clause 89, wherein the predetermined time is one or less of the following times: 1 second, 950 milliseconds, 900 milliseconds, 850 milliseconds, 800 milliseconds, 750 milliseconds, 700 milliseconds, 650 milliseconds, 600 milliseconds, 550 milliseconds, 500 milliseconds, 450 milliseconds, 400 milliseconds. Item 91: A method for processing a fluid according to item 89 or 90, wherein the predetermined time is one or more of the following times: 1 millisecond, 5 milliseconds, 10 milliseconds, 20 milliseconds, 25 milliseconds, 50 milliseconds, 100 milliseconds, 150 milliseconds, 200 milliseconds, 300 milliseconds. Item 92: A method for processing a fluid according to any one of items 89 to 91, wherein the first fluid substance and the second fluid substance are selected such that the fluid substance mixture obtained from mixing the first fluid substance with the second fluid substance has an intermediate state, for example during and / or immediately after mixing of the first fluid substance with the second fluid substance. Item 93: A method for treating a fluid according to item 92, wherein the intermediate state is a temporary state, e.g., a state that exists for less than a predetermined time. Item 94: A method for processing a fluid according to any one of items 89 to 93, wherein a first fluid substance and a second fluid substance are guided through a mixing region for a time of at least 10 milliseconds to 80 milliseconds, for example 20 milliseconds to 60 milliseconds, to form a fluid substance mixture. Paragraph 95: directing the first fluid material to the mixing region includes directing the first fluid material through a first fluid path of a fluid path system; and / or 95. A method for processing a fluid as described in any one of paragraphs 89 to 94, wherein directing the second fluid material to the mixing region comprises directing the second fluid material through a second fluid path of the fluid path system. Section 96: Directing the fluid material mixture through a directing region located downstream of the mixing region to direct the fluid material mixture toward a non-directing flow region. 96. A method for treating a fluid according to any one of paragraphs 89 to 95, further comprising: Section 97: directing the fluid substance mixture in a fluid directing element of the fluid path system located downstream of the non-directing flow region; and / or receiving the fluid material mixture into a fluid retention element of the fluid path system located downstream of the non-guided flow region; 96. A method for treating a fluid according to any one of paragraphs 89 to 95, further comprising: Item 98: A method for processing a fluid according to any one of items 89 to 97, further comprising the step of simultaneously directing the first fluid and the second fluid into a mixing region. Item 99: A method for processing a fluid according to any one of items 89 to 98, further comprising driving the fluid flow of the first fluid material with a first flow driver, e.g., a pump, e.g., a syringe pump, a peristaltic pump, a pressurized vessel, a diaphragm pump, and / or a piston pump. Item 100: A method for processing a fluid according to any one of items 89 to 99, further comprising driving the fluid flow of the second fluid material with a second flow driver, such as a pump, for example a syringe pump, a peristaltic pump, a pressurized vessel, a diaphragm pump, and / or a piston pump. Item 101: A method for processing a fluid according to any one of items 89 to 100, further comprising driving the flow of the fluid material mixture downstream of the non-guided flow region with a mixture flow driver, for example a pump, such as a syringe pump, peristaltic pump, diaphragm pump, and / or piston pump, or a pressurized vessel. Item 102: A method for processing a fluid according to any one of items 89 to 101, comprising moving a fluid material mixture through a free fall or free flow region, the free fall or free flow region being a non-guided flow region. Section 103: Fluid handling systems must be able to handle fluids with a density of 1 g / cm 3 103. A method for processing a fluid as described in any one of paragraphs 89 to 102, configured to be operated at a flow rate and / or have a flow path diameter such that, for water having a viscosity of 1 cP and a temperature of 20°C, the relationship between flow rate and flow path diameter results in a flow characterized by a calculated Reynolds number (Re) at the mixing region, the directing region, the first inlet of the first fluid path, the second inlet of the second fluid path, and / or the outlet of the mixing region of no more than one of the following values: 10,000, 7,500, 5,000, 4,000, 3,000, 2,900, 2,800, 2,700, 2,600, 2,500. Clause 104: Fluid handling systems must be able to handle fluids with a density of 1g / cm 3 104. A method for processing a fluid as described in any one of paragraphs 89 to 103, configured to be operated at a flow rate and / or have a flow path diameter such that, for water having a viscosity of 1 cP and a temperature of 20°C, the relationship between flow rate and flow path diameter results in a flow characterized by a calculated Reynolds number (Re) at the mixing region, the directing region, the first inlet of the first fluid path, the second inlet of the second fluid path, and / or the outlet of the mixing region of one or more of the following values: 500, 1000, 1100, 1200, 1300, 1400, 1500, 1700, 1800, 1900, 2000. Clause 105: A method for processing a fluid according to any one of clauses 89 to 104 carried out using a fluid handling system according to any one of clauses 1 to 88. Clause 106: Use of a fluid handling system according to any one of clauses 1 to 88 for mixing a first fluid substance with a second fluid substance to obtain a fluid substance mixture. Item 107: A fluid substance mixture obtainable or obtained by a fluid treatment method according to any one of items 89 to 106. [Explanation of symbols]

[0272] 20 Prior art tube 100 Fluid Handling System 202 First fluid path 204 Second Fluid Path 206 First Flow Driver 208 Second Flow Driver 300 mixed area 302 Mixing area (first) entrance 304 Mixing Zone (Second) Inlet 304a, 304b Second entrance 306 Mixed Parts 400 Non-inductive flow region 402 Non-inductive flow region wall 404 Non-inductive flow region wall 406 Fluid Induction Element 408a, 408b Fluid path widening portion 410 Entrance area 500 Orientation Area 600 free fall area 602 First Reservoir 604 Second Reservoir 700 reservoir area 702 Surface 704 Droplets of fluid substance mixture 706 Exit 708 Mixture Flow Driver DP1 Sediment DP2 deposits AR1 Fluid substance mixture flow direction AR2 Fluid flow of first fluid material AR3 Fluid flow of a second fluid material AR4 Inlet flow direction AR6 Inlet flow direction AR7 Non-inductive flow region principal axis F1 First fluid substance F2 Second fluid substance MX fluid substance mixture S1 First method step S2 Second method step

Claims

1. a fluid path system, a first fluid path for directing a first fluid substance towards a mixing region of the fluid path system; a second fluid path for directing a second fluid substance towards the mixing region; a mixing region arranged in fluid communication with the first fluid path and the second fluid path such that the first fluid material and the second fluid material can mix in the mixing region to form a fluid material mixture, A fluid handling system comprising a non-guiding flow region, the non-guiding flow region being capable of or configured to prevent contact of the fluid material mixture with an inner wall suitable for guiding the flow of the fluid material mixture along a flow direction of the fluid material mixture while the fluid material mixture moves through the non-guiding flow region, and the non-guiding flow region extending for a predetermined distance downstream of the mixing region, e.g. extending for only a predetermined distance.

2. The fluid handling system of claim 1 , wherein a fluid directing or fluid retaining element is positioned downstream of the non-directing flow region to receive and / or direct the fluid material mixture.

3. 3. A fluid handling system according to claim 1 or 2, configured to allow the first and second fluid materials to move simultaneously to the mixing region.

4. 4. A fluid handling system according to claim 1, wherein the fluid pathway system comprises a directing region positioned between the mixing region and the non-guiding flow region, viewed along the flow direction of the fluid material mixture, the directing region being configured to determine an inlet flow direction of the fluid material mixture in which the fluid material mixture flows into the non-guiding flow region.

5. 5. A fluid handling system as claimed in any one of claims 1 to 4, having a free fall or free flow region that allows the fluid material mixture to move within the fluid handling system without contacting an inner wall of the fluid handling system, for example the inner wall closest to the fluid material mixture, for a predetermined distance, for example due to an interruption of the fluid path system in a non-guiding flow region and / or due to a mixture fluid path of the fluid path system being configured with an appropriate width in the non-guiding flow region.

6. 6. A fluid handling system according to any one of claims 1 to 5, wherein the predetermined distance is selected such that contact of the fluid substance mixture with the inner wall is prevented or prevented for a predetermined period of time, for example during operation of the fluid handling system.

7. 7. A fluid handling system according to claim 6, wherein the predetermined time is one or less of: 1 second, 950 milliseconds, 900 milliseconds, 850 milliseconds, 800 milliseconds, 750 milliseconds, 700 milliseconds, 650 milliseconds, 600 milliseconds, 550 milliseconds, 500 milliseconds, 450 milliseconds, 400 milliseconds; and / or wherein the predetermined time is one or more of: 1 millisecond, 5 milliseconds, 10 milliseconds, 20 milliseconds, 25 milliseconds, 50 milliseconds, 100 milliseconds, 150 milliseconds, 200 milliseconds, 300 milliseconds.

8. 8. A fluid handling system according to any one of claims 1 to 7, wherein the first fluid material and the second fluid material are selected so that the fluid material mixture resulting from mixing the first fluid material and the second fluid material has an intermediate state, for example during and / or immediately after mixing of the first fluid material and the second fluid material.

9. 9. A fluid handling system according to claim 8, wherein the intermediate state is a temporary state, for example a state that exists for less than a predetermined time.

10. 10. A fluid handling system according to claim 8 or 9, wherein the fluid substance mixture has a greater tendency in its intermediate state to form deposits on walls, for example internal walls defining the fluid pathway, than in the steady state.

11. 11. A fluid handling system according to any one of claims 8 to 10, wherein the fluid handling system is configured such that the fluid material mixture, in its intermediate state, flows through a non-guided flow region.

12. 12. A fluid handling system according to any one of claims 8 to 11, configured and / or operable to cause the fluid substance mixture, in its intermediate state, to flow only through the mixing region and / or the non-guiding flow region and / or optionally the directing region.

13. 13. A fluid handling system according to any preceding claim, wherein the first fluid material and the second fluid material are selected to form a fluid material mixture comprising colloids, for example having an average colloidal particle size of 10 nm or more and / or 1000 nm or less.

14. 14. A fluid handling system according to any preceding claim, wherein the first fluid substance comprises a nucleic acid, a peptide, or a protein.

15. 15. A fluid handling system according to any preceding claim, wherein the second fluid substance is a colloidal suspension, such as an ionic colloidal suspension, such as a cationic colloidal suspension.

16. 16. A fluid handling system according to any one of claims 1 to 15, wherein the fluid handling system is configured such that the fluid material mixture is guided downstream of the non-guiding flow region towards an outlet of the fluid handling system or fluid pathway system which allows the fluid material mixture to be continuously withdrawn from the non-guiding flow region, for example via an outlet, from the fluid handling system.

17. 17. A fluid handling system as claimed in any one of claims 1 to 16, wherein the fluid path system has an increased diameter of the mixture fluid path of the fluid path system in the non-guided flow region, thereby enabling non-guided flow of the fluid material mixture in the non-guided flow region.

18. 18. The fluid handling system of claim 17, wherein the diameter of the mixture fluid path varies in the non-guided flow region.

19. the diameter of the mixture fluid path increases in the non-guiding flow region in a direction away from the mixing region, e.g., in at least a portion of the mixture fluid path, and / or continuously; or 19. A fluid handling system according to claim 17 or 18, wherein the diameter of the mixture fluid path decreases in the non-guiding flow region in a direction away from the mixing region, e.g., along at least part of the mixture fluid path and / or continuously.

20. 20. A fluid handling system according to claim 1, wherein the mixing region is formed by a mixing element connected to a first tube defining a first fluid path and / or a second tube defining a second fluid path.

21. 21. A fluid handling system according to any preceding claim, configured to provide turbulent mixing of the first and second fluid materials in the mixing region.

22. directing a first fluid material and a second fluid material in the fluid path system to a mixing region to form a fluid material mixture; preventing contact of the fluid material mixture with walls of the fluid path system for a predetermined time in a non-guiding flow region along the flow direction of the fluid material mixture downstream of the mixing region.

1. A method for processing a fluid, comprising:

23. 23. The method for processing a fluid of claim 22, wherein the predetermined time is less than or equal to one of 1 second, 950 milliseconds, 900 milliseconds, 850 milliseconds, 800 milliseconds, 750 milliseconds, 700 milliseconds, 650 milliseconds, 600 milliseconds, 550 milliseconds, 500 milliseconds, 450 milliseconds, 400 milliseconds, and / or the predetermined time is one or more of 1 millisecond, 5 milliseconds, 10 milliseconds, 20 milliseconds, 25 milliseconds, 50 milliseconds, 100 milliseconds, 150 milliseconds, 200 milliseconds, 300 milliseconds.

24. 24. A method for processing a fluid as claimed in claim 22 or 23, wherein the first fluid substance and the second fluid substance are selected such that the fluid substance mixture resulting from mixing the first fluid substance and the second fluid substance has an intermediate state, for example during and / or immediately after mixing of the first fluid substance and the second fluid substance.

25. 15. The method for treating a fluid according to claim 14, wherein the intermediate state is a temporary state, e.g., a state that exists for less than a predetermined time.

26. 26. A method for processing a fluid as claimed in any one of claims 22 to 25, wherein the first fluid material and the second fluid material are directed through a mixing region for a time of at least 10 milliseconds to 80 milliseconds, for example 20 milliseconds to 60 milliseconds, to form a fluid material mixture.

27. 27. A method for processing a fluid as described in any one of claims 22 to 26, further comprising directing the fluid material mixture through a directing region located downstream of the mixing region to direct the fluid material mixture towards a non-directing flow region.

28. 28. The method for treating a fluid according to any one of claims 22 to 27, further comprising simultaneously directing the first fluid and the second fluid into a mixing region.

29. 29. A method for processing a fluid as claimed in any one of claims 22 to 28, further comprising moving the fluid material mixture through a free fall or free flow region, wherein the free fall or free flow region is a non-guided flow region.

30. 30. A method for processing a fluid according to any one of claims 22 to 29 carried out using a fluid handling system according to any one of claims 1 to 21.

31. 22. Use of a fluid handling system according to any one of claims 1 to 21 for mixing a first fluid substance with a second fluid substance to obtain a fluid substance mixture.

32. 31. A fluid substance mixture obtainable or obtained by a method for treating a fluid according to any one of claims 22 to 30.

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