Fluid treatment system and method

Abstract

A fluid treatment system includes a fluid path system including a first fluid path for directing a first fluid substance to a mixing zone of the fluid path system, a second fluid path for directing a second fluid substance to the mixing zone, wherein the mixing zone is arranged in fluid communication with the first fluid path and the second fluid path such that the first fluid substance and the second fluid substance can be mixed in the mixing zone to form a fluid substance mixture, and wherein the fluid treatment system comprises a non-directed flow zone, wherein the non-directed flow zone is configured such that when the fluid substance mixture flows through the non-directed flow zone, the fluid substance mixture can contact or be prevented from contacting an inner wall adapted to direct the fluid substance mixture to flow in a flow direction of the fluid substance mixture, and wherein the non-directed flow zone extends a predetermined distance downstream of the mixing zone, e.g., only the predetermined distance.

Description

Background Art

[0001] The present disclosure relates to improvements relating to fluid treatment systems and methods for treating fluids in fluid treatment systems.

[0002] The object of the present disclosure is to provide an improved fluid treatment system for treating a fluid, for example for mixing at least two fluids with each other. The improvements may also relate to methods for treating a fluid and the use of a fluid treatment system for treating a fluid and a fluid substance mixture obtained from said fluid.

[0003] These and / or other objects are achieved by the subject matter disclosed herein and / or by the subject matter set out in the appended independent claims, as will become apparent from the following description. Advantageous embodiments and improvements are defined, among others, by the dependent claims. Summary of the Invention

[0004] A first aspect of the present disclosure relates to a fluid treatment system for treating a first fluid substance and a second fluid substance and for providing or forming a fluid substance mixture. Another aspect of the present disclosure relates to a method for treating a fluid, such as by mixing a first fluid substance and a second fluid substance, optionally for the fluid substance mixture. The method can be implemented with the fluid treatment system of the first aspect; however, other fluid treatment systems can also be applied. Another aspect of the present invention relates to the application of a fluid treatment system for providing a fluid substance mixture, such as by mixing a first fluid substance and a second fluid substance and / or adopting the method described herein. The fluid treatment system can be the fluid treatment system of the first aspect.

[0005] It is noteworthy that the features disclosed herein in relation to the method also apply to the fluid treatment system and / or application, and the features disclosed herein for the application and fluid treatment system also apply to the method. In general, the features disclosed in relation to different aspects, embodiments or implementations can be combined with another feature, even if the combination is not explicitly described herein. Unless otherwise expressly stated, the features disclosed above and below herein apply to all aspects, embodiments or implementations of the invention, such as the fluid treatment system, method and application. For example, if method-like features are described, they should be understood to also relate to a fluid treatment system configured for implementing or operating these features, such as a fluid treatment system configured to or capable of providing flow in a mixing zone (e.g., in an equivalent manner to that described below in relation to the fluid treatment system).

[0006] In one embodiment, the fluid treatment system comprises a fluid path system. The fluid path system comprises a first fluid path for guiding a first fluid substance (also referred to herein as the first fluid) to the mixed zone of the fluid path system. The fluid path system also comprises a second fluid path for guiding a second fluid substance (also referred to herein as the second fluid) to the mixed zone of the fluid path system. The fluid path system can also comprise an additional fluid path for guiding an additional fluid substance to the mixed zone of the fluid path system, for example, guiding a 3rd fluid path of a 3rd fluid substance to the mixed zone of the fluid path system, for example, a gas such as air.

[0007] Hereinafter, a fluid handling system for a fluid path system will be described, the fluid path system comprising a first fluid path and a second fluid path for a first fluid substance and a second fluid substance, respectively. However, the system is not limited to only two fluid substances, and features associated with the first and / or second fluid paths and / or the first and / or second fluid substances also apply to additional fluid paths and / or fluid substances, such as a third fluid path and / or a third fluid substance.

[0008] The mixed zone is arranged to be in communication with the first fluid path and the second fluid path fluid, for example, simultaneously, so that the first fluid substance and the second fluid substance can be mixed in the mixed zone to form a fluid substance mixture. Until the mixed zone, the fluid path is easily separated from the other fluid path fluid. The fluid treatment system can be composed of or comprise the fluid path system. The present invention further relates to such a fluid path system.

[0009] The mixing zone may be configured to allow mixing of the first and second fluid substances, for example by its shape and / or position relative to the first and second fluid paths.The first and second fluids may enter the mixing zone simultaneously.

[0010] In embodiments, the fluid treatment system includes a non-guided flow zone. The non-guided flow zone is configured so that when the fluid substance mixture flows through the non-guided flow zone, the fluid substance mixture can contact an inwall or stop the fluid substance mixture from contacting the inwall, and the inwall is suitable for guiding the fluid substance mixture to flow along the flow direction of the fluid substance mixture. This can be achieved by various measures. An example is to widen the fluid path so that the fluid flow can not contact the inwall of the fluid path system. Therefore, there can be an inwall that defines the fluid path laterally (for example, around relative to the flow direction), but when passing through the non-guided flow zone, the fluid flow (of the fluid substance mixture) does not contact the inwall. Another example is to interrupt the fluid path system in the non-guided flow zone. In this case, there is no inwall that can contact the fluid flow (of the fluid substance mixture).

[0011] In embodiments, the non-guided flow zone extends a predetermined distance downstream of the mixing zone, for example, only extends the predetermined distance.The non-guided flow zone can be the zone of the fluid treatment system, for example, the zone of the fluid path system, wherein the fluid substance mixture can flow in a non-guided manner (for example, freely).The fluid treatment system can be configured so that the fluid substance mixture is not limited to the guiding of direction when flowing through the non-guided flow zone.The flow direction of the fluid substance mixture in the non-guided flow zone can be determined (for example, uniquely determined) by the gravity of the fluid substance mixture when the fluid substance mixture enters the non-guided flow zone by the direction and (for example, only) by the fluid substance mixture in the non-guided flow zone. Therefore, in the non-guided flow zone, the change of all directions (if any) of the fluid flow of the fluid path system during operation or use of the fluid treatment system can be controlled by gravity.In the non-guided flow zone, preferably, the inwall of the fluid substance mixture and the fluid path system does not contact.

[0012] In other words, in the present disclosure, any change in the flow direction of the fluid substance mixture in the non-guided flow area and / or at least within a predetermined distance of the non-guided flow area can be obtained (e.g. only) by gravity acting on the fluid substance mixture.

[0013] A fluid substance mixture within the meaning of the present disclosure may be a fluid substance (eg a liquid) resulting from the mixing of at least two fluid substances (eg a first fluid substance and a second fluid substance).

[0014] Proved that non-guided flow zone is particularly advantageous, for example, for fluid substance mixture, it shows transition state or intermediate state, for example, immediately after described fluid substance has been mixed into described fluid substance mixture.After (temporarily) intermediate or transition state, described fluid substance mixture can present final state.Described transition state can be the as yet undetermined state of the final and / or stable physicochemical characteristic of described fluid substance mixture.Under described final state, described fluid substance mixture can have stable (for example constant) characteristic.Described final state can be stable state.Under described transition state or intermediate state, described fluid substance mixture can show higher deposition tendency at the inwall place of described fluid path.

[0015] In the transition state of fluid substance mixture, the contact of described fluid substance mixture and any element can increase the possibility of the unwanted variation of the physicochemical characteristic of described fluid substance mixture.Therefore, it has been proved that advantageously, the non-guided flow zone of extending predetermined distance is provided, in described non-guided flow zone, described fluid substance mixture does not contact any wall during its transition period or state, for example any inwall of described fluid path system.For example, in the production process of nanoparticle composition, after having determined the condition that nanoparticle forms, the fluid substance mixture used can increase the tendency of directly depositing on the inwall of fluid path system, for example, by mixing described first fluid substance mixture and second fluid substance mixture.Therefore, described predetermined distance can be selected easily to guarantee during nanoparticle formation, before contacting inwall (as, before non-guided flow zone ends) finishes the transition state that surface has high affinity (for example the high tendency of forming sediment on the surface).

[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 liposome nanoparticles (LNP), (ionizable) lipid complexes (lipoplexes, LPX), (ionizable) polyplexes (polyplexes, PPX).

[0017] According to at least one embodiment, a fluid guiding element or a fluid retaining element of the fluid treatment system is located downstream of the non-guided flow zone to receive and / or guide the fluid substance mixture.

[0018] When being received and / or guided by described fluid guiding element or being received by described fluid retaining element, described fluid substance mixture may not be in transitional state or intermediate state.Therefore, when described fluid substance mixture passes through described non-guided flow zone, described fluid substance mixture preferably presents its stable state.According to at least one embodiment, described fluid handling system is configured so that described first fluid substance and described second fluid substance can move to described mixing zone simultaneously.These materials can mix immediately after they enter mixing zone.

[0019] 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 0.5 mm and / or less than or equal to 5.5 cm. The diameter may be greater than or equal to any 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 may be less than or equal to any 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 path and / or the diameter of the second fluid path may be between 0.5 mm and 45 mm. The diameter of the first fluid path and / or the diameter of the second fluid path may be greater than or equal to 15.6 mm and / or less than or equal to 12.8 mm. The diameter of the first fluid path and / or the diameter of the second fluid path may be 50.8 mm.

[0020] 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" and / or less than or equal to 2", measured in fractions of an inch (e.g., SAE (Standard Automotive Engineers)). The diameter may be greater than or equal to any of the following: 1 / 32", 1 / 16", 1 / 8", 1 / 4", 3 / 4", 1 / 2", 1", 11 / 32", 11 / 16", 11 / 8", 11 / 4", 13 / 4", 11 / 2", 2". Alternatively or additionally, the diameter may be less than or equal to any of: 1 / 32", 1 / 16", 1 / 8", 1 / 4", 3 / 4", 1 / 2", 1", 1 1 / 32", 11 / 16", 11 / 8", 11 / 4", 13 / 4", 11 / 2", 2".

[0021] The diameter of the first fluid path and the diameter of the second fluid path may be equal to or different from each other.

[0022] According to at least one embodiment, fluid flow of the first fluid substance along the first fluid path is actuatable or driven by a first flow driver, such as a pump, such as a syringe pump, peristaltic pump, diaphragm pump and / or piston pump or a pressurized container.

[0023] According to at least one embodiment, the fluid flow of the second fluid substance along the second fluid path is drivable or driven by a second flow driver, such as a pump, such as a syringe pump, peristaltic pump, diaphragm pump and / or piston pump or a pressurized container.

[0024] According to at least one embodiment, the fluid flow of the fluid substance mixture downstream of the non-guided flow zone is drivable or driven by a mixture flow driver, such as a pump, such as a syringe pump, peristaltic pump, diaphragm pump and / or piston pump or a pressurized container.

[0025] According to at least one embodiment, the fluid path system includes a guide area. The guide area can be arranged between the mixing zone and the non-guided flow area along the flow direction of the fluid substance mixture. The guide area can be configured to determine the incoming flow direction of the fluid substance mixture, and the fluid substance mixture enters the non-guided flow area along this direction. In this way, it is possible to ensure that the flow of the fluid substance mixture is directed to the non-guided flow area to avoid contacting the fluid substance mixture with the wall (e.g., inwall) of the non-guided flow area.

[0026] According to at least one embodiment, the guide area has a length less than or equal to one of the following values: 10 cm, 9 cm, 8 cm, 7 cm, 6 cm, 5 cm, 4 cm, 3.5 cm, 3 cm, 2.5 cm, 2 cm, 1.5 cm, 1 cm, 0.5 cm, 0.4 cm, 0.3 cm, 0.2 cm, 0.1 cm.

[0027] According to at least one embodiment, the guide area has a length greater than or equal to one 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.

[0028] The guide area may have a length of 0.05 cm to 10 cm. In particular, the guide area may have a length of 2.2 cm.

[0029] According to at least one embodiment, the incoming flow direction is parallel to the main axis of the non-guided flow zone.

[0030] According to at least one embodiment, the incoming flow direction is angled relative to a major axis of the non-guided flow zone.

[0031] In both cases, ie parallel or angled, the guide area is arranged such that the fluid substance mixture exiting the guide area into the non-guided flow area is prevented from contacting inner walls suitable for guiding the flow in the non-guided flow area.

[0032] According to at least one embodiment, the fluid path of the fluid path system guiding the fluid substance mixture widens as seen in the flow direction from the mixing zone to the non-guided flow zone (in the flow direction away from the mixing zone), for example at the end of the guided zone.

[0033] According to at least one embodiment, the fluid treatment system has a free fall zone or free flow zone, for example for a predetermined distance, for example due to an interruption of the fluid path system in the non-guided fluid zone and / or due to the mixture fluid path of the fluid path system being configured to have an appropriate width in the non-guided flow zone. The free flow zone can allow the fluid substance mixture to flow within the fluid treatment system without contacting the inner wall of the fluid treatment system (e.g., the inner wall closest to the fluid substance mixture). According to at least one embodiment, the fluid path system defines a first flow direction in which the first fluid substance flows from the first fluid path to the mixing zone through a first inlet, and the fluid path system defines a second flow direction in which the second fluid substance flows from the second fluid path to the mixing zone through a second inlet. The first flow direction and the second flow direction can define an angle. The angle can be in the range of 45° to 315°, for example in the range of 60° to 300°, for example 120° to 270° or about 180°.

[0034] According to at least one embodiment, described mixing zone can comprise more than one (for example two) first inlet of the first fluid path for the first fluid material, and / or more than one (for example two) second inlet of the second fluid path for the second fluid material.So described mixing zone, can for example have three inlets, the first fluid material and the second fluid material enter described mixing zone by described inlet, for example, two first inlets for the first fluid material and a second inlet for the second fluid material.Comprise in mixing zone the embodiment of more than one first inlet and / or more than one second inlet that are respectively used for the first fluid material and the second fluid material, the first fluid material and the second fluid material can move in described mixing zone simultaneously.

[0035] According to at least one embodiment, the mixing zone may comprise one or more further inlets for further fluid paths of further fluid substances, such as one or more tertiary inlets for a tertiary fluid path of a tertiary fluid substance, such as air.

[0036] All features of the first fluid path and / or second fluid path and the first fluid substance and / or second fluid substance associated with the embodiment described herein in which the mixing zone comprises a first inlet for a first fluid substance and a second inlet for a second fluid substance may also apply to embodiments in which the mixing zone has one or more first inlets and / or one or more second inlets and / or one or more additional inlets (e.g., a third inlet).

[0037] According to at least one embodiment, the mixing zone has an outlet for the fluid substance mixture and / or the non-guided flow zone comprises an inlet zone.

[0038] According to at least one embodiment, the inner diameter of the outlet or inlet zone 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.

[0039] The inner diameter of the outlet or the inlet area may be greater than or equal to 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, or 60 mm. The inner diameter of the outlet or the inlet area may be less than or equal to 60 mm, 55 mm, 50 mm, 45 mm, 40 mm, 35 mm, 30 mm, 25 mm, 20 mm, 15 mm, 10 mm, 5 mm, or 0.5 mm. For example, less than or equal to 52 mm.

[0040] The inner diameter of the outlet or the inlet zone may for example be between 1 mm and 60 mm, such as between 30 mm and 52 mm.

[0041] According to at least one embodiment, the entry zone of the non-guided flow zone is adjacent to or coincides with the exit zone of the guided zone.

[0042] If the fluid treatment system does not include a guide zone, the entry zone of the non-guided flow zone may be adjacent to or coincide with the outlet of the mixing zone. In this case, the outlet of the mixing zone may be arranged so that the fluid substance mixture flowing out of the outlet of the mixing zone enters the non-guided flow zone in a manner that prevents the fluid substance mixture from contacting an inner wall suitable for guiding flow in the non-guided flow zone.

[0043] According to at least one embodiment, the predetermined distance is greater than or equal to one of the following values: 5cm, 6cm, 7cm, 8cm, 9cm, 10cm, 11cm, 12cm, 13cm, 20cm, 35cm, 50cm, 80cm, 100cm, 200cm. Alternatively or additionally, the predetermined distance is less than or equal to one of the following values: 600cm, 565cm, 550cm, 500cm, 450cm, 400cm, 300cm, 200cm, 165cm, 68cm, 35cm, 30cm, 25cm, 20cm, 15cm, 13cm. Thus, the predetermined distance can be 5cm to 565cm or 600cm, for example 5cm to 13cm.

[0044] According to at least one embodiment, the predetermined distance is selected such that the fluid substance mixture (eg, at a predetermined flow rate of the substance mixture) has most or all of its intermediate or transitional state within the non-guided flow region.

[0045] According to at least one embodiment, the predetermined distance is selected so that the fluid material mixture flows through the non-guided flow zone for at least a predetermined time period. The predetermined time period can be a time characteristic of the time required for the fluid material mixture to reach a stable or final state. For example, the predetermined time period can be greater than the time required to reach a stable or final state, or greater than 80% of the time required for the fluid material mixture to exhibit its stable state.

[0046] According to at least one embodiment, the predetermined time period is less than or equal to one of: 1s, 950ms, 900ms, 850ms, 800ms, 750ms, 700ms, 650ms, 600ms, 550ms, 500ms, 450ms, 400ms.

[0047] According to at least one embodiment, the predetermined time period is greater than or equal to one of: 1 ms, 5 ms, 10 ms, 20 ms, 25 ms, 50 ms, 100 ms, 150 ms, 200 ms, 300 ms.

[0048] According to at least one embodiment, the fluid handling system is configured to operate at a flow rate and / or have a diameter of the flow path such that for a flow rate of 1 g / cm 3 of water with a density of 1 cP, a viscosity of 1 cP and a temperature of 20°C, the relationship between the flow rate and the diameter of the flow path results in the flow at the mixing zone, the guide zone, the first inlet, the second inlet and / or the outlet (e.g., the outlet of the mixing zone) being characterized in that the calculated Reynolds number (Re) is greater than or equal to one of the following values: 500, 1000, 1100, 1200, 1300, 1400, 1500, 1700, 1800, 1900, 2000.

[0049] According to at least one embodiment, the fluid handling system is configured to operate at a flow rate and / or have a diameter of the flow path such that for a flow rate of 1 g / cm 3 of water with a density of 1 cP, a viscosity of 1 cP and a temperature of 20°C, the relationship between the flow rate and the diameter of the flow path results in the flow at the mixing zone, the guide zone, the first inlet, the second inlet and / or the outlet (e.g., the outlet of the mixing zone) being characterized in that the calculated Reynolds number (Re) is less than or equal to one of the following values: 10000, 7500, 5000, 4000, 3000, 2900, 2800, 2700, 2600, 2500.

[0050] According to at least one embodiment, the fluid handling system is capable of handling or providing a fluid flow having a Reynolds number (Re) of 500 to 10,000, e.g., 500 to 3,000, e.g., 1,700 to 2,500 (e.g., at the mixing zone, the guide zone, the first inlet, the second inlet, and / or the outlet).

[0051] The Reynolds number is used to classify the flow of fluids, such as liquids. The Reynolds number R for a fluid flow can be calculated using the following formula: R = V D / Vis_kin, Where V is the fluid flow velocity (m / s, meters per second), D is the characteristic distance (e.g., the diameter of the flow path guiding the fluid flow, such as the inner diameter of a conduit, m (meters)), Vis_kin is the kinematic viscosity (m 2 Kinematic viscosity is calculated by dividing the (dynamic) viscosity of the fluid (Vis_dyn, Pascal seconds (Pa s)) by the density of the fluid (e.g. kg / m 3 ). The velocity V can be derived from the flow rate by dividing the flow rate by the cross-sectional area of ​​the flow path through which the fluid flows (e.g., defined as ml / min, i.e., milliliters per minute). 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 fluid path such as an outlet, conduit, or pipe.

[0052] In order to determine the Reynolds number of the fluid flow leaving the mixing zone and / or at the outlet of the mixing zone or mixing component, the characteristic values ​​of the first and second fluids can be used (if applicable, weighted by the coefficient that determines the contribution of the flow rate of the first and second fluids into the mixing chamber to the total flow of the first and second fluids). Therefore, the respective Reynolds number of the fluid material mixture flow discussed herein can be related to the value of the relevant quantity calculated as described below or the Reynolds number based on the value of the relevant quantity that has been measured. For the fluid material mixture, that is, after the first fluid material and the second fluid material have been mixed, the Reynolds number can be calculated by using the following: V = (F_1 + F_2) / ((D / 2)2 π), where D is the internal diameter of the flow path at the relevant location (e.g. at the outlet of the mixing zone), F_1 is the flow rate of the first fluid species entering the mixing zone, and F_2 is the flow rate of the second fluid substance entering the mixing zone (the sum of F_1 and F_2 is the flow rate of the fluid substance mixture at the outlet of the mixing zone).

[0053] Vis_dyn = F_1 / (F_1 + F_2) Vis_1 + F_2 / (F_1 + F_2) Vis_2, in Vis_1 is the (dynamic) viscosity of the first fluid substance, Vis_2 is the (dynamic) viscosity of the second fluid substance.

[0054] D_L = F_1 / (F_1 + F_2) D_1 + F_2 / (F_1 + F_2) D_2, in D_1 is the density of the first fluid substance, D_2 is the density of the second fluid substance.

[0055] Vis_kin = Vis_dyn / D_L

[0056] Then, the Reynolds number is given by: R = V D / Vis_kin The Reynolds number is a dimensionless quantity that can be used to quantify fluid flow without requiring specific dimensions of the conduit or other values ​​of fluid properties such as flow rate, viscosity, density, etc.

[0057] According to at least one embodiment, 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 the first fluid substance and the second fluid substance.

[0058] According to at least one embodiment, the intermediate state is a transient state, eg, a state that exists only for less than a predetermined period of time.

[0059] According to at least one embodiment, the fluid substance mixture exhibits a stable state after the intermediate state.

[0060] According to at least one embodiment, a fluid substance mixture in an intermediate state is more prone to forming deposits on interior walls (eg, interior walls defining a fluid path) than a fluid substance mixture in a stable state.

[0061] The intermediate state may also be colloquially referred to as a "viscous phase" because it is the state of the fluid substance mixture in which deposits tend to form on the walls (i.e., "stick" to the walls), and the fluid substance mixture may cause blockages in any pipes as it passes through the pipes in its intermediate state. As the processing volume increases, the intermediate state may cause blockages in the flow path, such as blockages in the flow path formed by the pipes, through which the fluid is completely blocked, thereby unintentionally blocking and destroying the production process of the fluid substance mixture. This will limit the volume that can be processed using a given fluid path system. Therefore, it is advantageous to avoid or reduce blockages, such as by providing a non-guided flow zone.

[0062] Furthermore, during processing, a portion of the sediment may separate, which can result in the size distribution of the nanoparticles changing over time (e.g., an uneven distribution of particle sizes). This is clearly detrimental to the end product (e.g., a fluid material mixture).

[0063] It would be advantageous to provide a fluid processing system having an unguided flow region in which the fluid material mixture does not contact any wall (e.g., any interior wall) during its intermediate state (e.g., viscous phase) (or at least for a period of time during its intermediate state, such as for a substantial portion of the duration of the intermediate state), thereby minimizing the likelihood of deposit formation and blockage. This can result in higher throughput during processing, a more homogeneous end product with a uniform distribution of particle sizes, and fewer failures during or during processing of the product.

[0064] For example, this may be achieved by a non-guided flow region (eg, a free-fall region) in which the fluid substance mixture is prevented from contacting any walls (eg, inner walls of the non-guided flow region).

[0065] According to at least one embodiment, the fluid handling system is configured such that the fluid substance mixture flows in the non-guided flow zone in its intermediate state, or at least for a period of time in its intermediate state.

[0066] According to at least one embodiment, the fluid handling system is configured and / or operable such that the fluid substance mixture in its intermediate state flows only in the mixing zone and / or the non-guided flow zone and / or optionally in the guided zone.

[0067] According to at least one embodiment, the first fluid material and the second fluid material are selected to form a fluid material mixture that comprises colloid, and described colloid for example has and is greater than or equal to 10nm and / or is less than or equal to 1000nm, for example 200 to 500nm, for example the average particle size of about 400nm.According to at least one embodiment, average particle size can be greater than or equal to 250nm and / or is less than or equal to 750nm.According to at least one embodiment, described average particle size can be greater than or equal to 60nm and / or is less than or equal to 140nm.According to at least one embodiment, described average particle size can be greater than or equal to 50nm and / or is less than or equal to 150nm.According to at least one embodiment, described average particle size can be greater than or equal to 10nm and / or is less than or equal to 300nm.

[0068] According to at least one embodiment, the first fluid substance and the second fluid substance are selected to form a fluid substance mixture that comprises colloid, and described colloid for example has the average particle size that is greater than or equal to 10nm, 20nm, 50nm, 100nm, 250nm, 300nm, 350nm, 400nm, 450nm, 500nm, 600nm, 650nm, 700nm. Additionally or alternatively, the first fluid substance and the second fluid substance are selected to form a fluid substance mixture that comprises colloid, and described colloid for example has the average particle size that is less than or equal to 750nm, 700nm, 650nm, 600nm, 550nm, 500nm, 450nm, 400nm, 350nm, 300nm, 250nm, 200nm, 150nm, 100nm, 50nm, 20nm.

[0069] The particle size may depend on the starting materials used.

[0070] According to at least one embodiment, the fluid handling system can operate with a processing volume greater than or equal to 50 mL, such as greater than or equal to 100 mL, 200 mL, 500 mL, 700 mL, or even greater than or equal to 900 mL or 1 L, or even greater than or equal to 10 L or 20 L, such as 12 L or 12.2 L, or even greater than or equal to 50 L or 100 L, or even greater than or equal to 500 L or 1000 L.

[0071] According to at least one embodiment, the fluid handling system can operate with a processing volume less than or equal to 1000L, 500L, 100L, 50L, 20L, for example, less than or equal to 500L, 400L, 300L, 12L, 10L, 2L, 1L, 700mL, 500mL, 200mL, or even less than or equal to 100mL or 50mL.

[0072] The fluid processing system may operate at a processing volume of 50 mL to 20 L, such as 2 L to 20 L, such as 12.2 L.

[0073] However, the fluid treatment system is not limited to any of these treatment volumes and may include treatment volumes greater than 1000 L, for example.

[0074] According to at least one embodiment, the processing is continuous, thereby having a theoretically unlimited processing volume, eg, the processing volume increases as long as the system is running.

[0075] According to at least one embodiment, the first fluid substance comprises ionic and / or ionizable substances.

[0076] According to at least one embodiment, the second fluid substance comprises ionic and / or ionizable substances.

[0077] According to at least one embodiment, the ionic species is a cationic species or an anionic species or a cationic and anionic species, such as a zwitterionic species.

[0078] According to at least one embodiment, the ionizable species is a cationic ionizable species or an anionic ionizable species or a cationic and anionic ionizable species, such as a zwitterionic ionizable species.

[0079] According to at least one embodiment, the ionic species of the first fluid substance is an anionic species and the ionic species of the second fluid substance is a cationic species.

[0080] According to at least one embodiment, the first fluid substance comprises a substance of polymeric nature, such as an ionic substance of polymeric nature.

[0081] According to at least one embodiment, the first fluid substance comprises nucleic acids, peptides or proteins.

[0082] According to at least one embodiment, the first fluid substance comprises RNA, such as mRNA, wherein optionally, the first fluid substance is an RNA solution.

[0083] According to at least one embodiment, the second fluid substance is a colloidal suspension, such as an ionic colloidal suspension, such as a cationic colloidal suspension.

[0084] According to at least one embodiment, the second fluid substance comprises a hydrophilic and / or lipophilic substance, such as an amphiphilic substance.

[0085] According to at least one embodiment, the second fluid substance comprises at least one lipid, such as a mixture of lipids.

[0086] According to at least one embodiment, the second fluid substance comprises liposomes.

[0087] According to at least one embodiment, the second fluid substance comprises a cationic polymer.

[0088] For example, but not limited to, the second fluid substance may comprise at least one lipid selected from the following: (i) an ionizable lipid, preferably an ionizable cationic lipid, for example an ionizable cationic amino lipid, such as ALC-0315 ((4-hydroxybutyl) azadiyl) bis(hexane-6,1-diyl) bis(2-hexyldecanoate)), or SM-102 (heptadecan-9-yl 8-((2-hydroxyethyl)(6-oxo-6-(undecanyloxy)hexyl)amino)octanoic acid), or DOPE (1,2-dioleoyl-sn-3-phosphatidylethanolamine), or DOTMA (N-(2,3-dioleoyloxy)propyl) N,N,N-trimethylammonium chloride), or DOSPA (N-(1-(2,3-dioleoyloxy)propyl)-N-(2-(sperminecarboxamido)ethyl)-N,N-dimethylammonium trifluoroacetate); (ii) non-cationic helper lipids or phospholipids, for example, neutral lipids such as DSPC (1,2-distearoyl-17-glycero-3-phosphocholine) or analogs or substitutes thereof; (iii) sterols or other structured lipids, such as cholesterol; and (iv) PEG lipids, such as 1,2-dimyristoyl-sn-glyceromethoxypolyethylene glycol (PEG-DMG). 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, alternatives to PEG lipids are not limited to the substances mentioned.

[0089] According to at least one embodiment, the first fluid substance and the second fluid substance are both colloidal suspensions, such as ionic colloidal suspensions.

[0090] According to at least one embodiment, the first fluid substance is or comprises a polymerized amphiphilic substance or a polymerized lipophilic substance or a polymerized hydrophilic substance, and wherein the second fluid substance comprises an amphiphilic substance or a polymerized amphiphilic substance or a polymerized lipophilic substance or a polymerized hydrophilic substance.

[0091] According to at least one embodiment, the first fluid substance and / or the second fluid substance are buffered. According to at least one embodiment, the first fluid substance and / or the second fluid substance are not buffered.

[0092] According to at least one embodiment, one of the first and second fluid substances or the fluid substance mixture is a pharmaceutical substance, such as a biopharmaceutical substance.

[0093] According to at least one embodiment, at least one or both of the first and second fluid substances are aqueous compositions, such as aqueous solutions or aqueous dispersions, or both the first and second fluid substances are aqueous compositions, such as aqueous solutions or aqueous dispersions.

[0094] According to at least one embodiment, at least one or both of the first fluid substance and the second fluid substance are solutions.

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

[0096] According to at least one embodiment, the first fluid substance is an aqueous composition, such as an aqueous solution or an aqueous dispersion, and the second fluid substance is an organic composition.

[0097] According to at least one embodiment, the organic composition is an organic solution or dispersion.

[0098] Organic compositions can be defined as compositions comprising, for example, greater than 1%, 10%, 25%, 50% organic solvent.

[0099] According to at least one embodiment, one or both of the first fluid substance and the second fluid substance is a medical fluid substance.

[0100] According to at least one embodiment, the fluid substance mixture is a colloidal suspension and / or comprises particles, for example nanoparticles. The particles can be formed by one or more components of the first fluid substance and one or more components of the second fluid substance. The particles can be any nanoparticles, for example polymer nanoparticles or particles comprising lipids and polymers, for example lipid or liposome nanoparticles (LNP), lipid complex (LPX), polyplex (PPX). The nanoparticle composition can comprise nucleic acids, for example RNA (ribonucleic acid), as mRNA (messenger ribonucleic acid) or DNA (deoxyribonucleic acid).

[0101] According to at least one embodiment, the nanoparticles can have a size (e.g., maximum, minimum, or average diameter) greater than or equal to 20nm, 50nm, 100nm, 250nm, 300nm, 350nm, 400nm, 450nm, 500nm, 600nm, 650nm, 700nm. According to at least one embodiment, the nanoparticles can have a size less than or equal to 750nm, 700nm, 650nm, 600nm, 550nm, 500nm, 450nm, 400nm, 350nm, 300nm, 250nm, 200nm, 150nm, 100nm, 50nm. Nanoparticles can have a size of 20nm to 1000nm, for example, 250nm to 750nm.

[0102] According to at least one embodiment, the first fluid path is fluidly connected or fluidically connectable to a first reservoir comprising a first fluid substance, such that the first fluid substance can be driven from the first reservoir through the first fluid path to the mixing zone, and / or the second fluid path is fluidly connected or fluidically connectable to a second reservoir comprising a second fluid substance, such that the second fluid substance can be driven from the second reservoir through the second fluid path to the mixing zone.

[0103] According to at least one embodiment, the fluid path system is a closed system. As used herein, 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 path system at any location within the fluid path system has an inner wall that externally delimits the fluid path system.

[0104] According to at least one embodiment, the fluid path system can be pressure balanced via a sterile filter. In other words, a sterile inlet and / or outlet for pressure equalization is allowed, for example via a sterile filter.

[0105] According to at least one embodiment, the fluid path system is an uninterrupted system. In this article, "uninterrupted" can be understood as making each element through which the first fluid substance, the second fluid substance and the fluid substance mixture pass physically connected to each other without any interruption.

[0106] According to at least one embodiment, the fluid handling system is an interrupted system. For example, the non-guided flow area can be physically connected to the guided area. However, an uninterrupted and / or closed system is preferred, for example to maintain sterility within the fluid path system.

[0107] According to at least one embodiment, the fluid treatment system comprises a reservoir area for collecting the fluid substance mixture, the reservoir area being arranged downstream of the non-guided flow area as seen along the flow direction of the fluid substance mixture in the fluid treatment system.

[0108] According to at least one embodiment, the fluid substance mixture forms a surface on a side of the reservoir area facing the non-guided flow area, eg seen in a direction opposite to the flow direction of the fluid substance mixture to the reservoir area, which surface defines the reservoir area.

[0109] According to at least one embodiment, the fluid handling system is configured such that the fluid substance mixture enters the reservoir region via the surface after passing through the non-guided flow region, for example impacting the surface in the form of fluid jets or fluid droplets.

[0110] According to at least one embodiment, the fluid handling system includes a reservoir region outlet in fluid communication with the reservoir region for removing contents, such as a fluid substance mixture, from the reservoir region.

[0111] According to at least one embodiment, the fluid substance mixture is in contact laterally with an inner wall delimiting the fluid treatment system in the reservoir region.

[0112] The fluid substance mixture may no longer assume its transition state, such as its intermediate state, in the reservoir area, so that the contact of the fluid substance mixture with the inner wall of the reservoir area may not change or at least not substantially change the physicochemical properties of the fluid substance mixture or its components (e.g., particles of nanoparticles, such as RNA of mRNA, lipids or lipid nanoparticles (LNP), lipid complexes (LPX), polyplexes (PPX)).

[0113] According to at least one embodiment, the fluid path system comprises the reservoir region.

[0114] According to at least one embodiment, the reservoir area is arranged within a container.

[0115] According to at least one embodiment, the storage area or the container has a volume greater than the mixing area. According to at least one embodiment, the storage area or the container has a volume smaller than the mixing area.

[0116] According to at least one embodiment, the container or the storage area has a fill capacity greater than or equal to 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.

[0117] According to at least one embodiment, the container or the storage area has a fill capacity 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 storage area may have a fill capacity of 0.5 L to 1000 L, such as 10 L to 500 L, such as 50 L.

[0118] According to at least one embodiment, the container (eg, bag) is collapsible and / or has flexible walls defining its interior, or the container (eg, flask) is non-collapsible and / or has rigid walls defining its interior.

[0119] According to at least one embodiment, at least a portion of the non-guided flow zone or the entire non-guided flow zone is within the container.

[0120] According to at least one embodiment, the fluid handling system (eg, container) includes a port for adding additional substances to the fluid substance mixture, such as downstream of the non-directed flow zone and / or in the container.

[0121] According to at least one embodiment, the fluid handling system is configured such that the fluid substance mixture is directed away from the non-guided flow zone downstream of the non-guided flow zone to an outlet of the fluid handling system or fluid path system, for example such that the fluid substance mixture can be continuously discharged from the fluid handling system via the outlet.

[0122] Directing the fluid mixture from the fluid treatment system can occur directly downstream of the non-directed flow zone, such that the fluid mixture exiting the non-directed flow zone is directed away. However, directing the fluid mixture from the fluid treatment system can also occur downstream of the reservoir zone. The fluid mixture from the reservoir zone can be directed to an outlet of the fluid treatment system or fluid routing system.

[0123] According to at least one embodiment, the fluid treatment system includes a mixture flow driver. The mixture flow driver can be a pump, for example, one of the above-mentioned pumps, or can be another type previously mentioned for the first flow driver or the second flow driver. The mixture flow driver can be configured to discharge the fluid substance mixture from the reservoir area, for example, to the outlet of the fluid path system and / or the fluid treatment system. Due to the non-guided flow area, the flow driver that drives the fluid to enter the non-guided flow area may not be suitable for driving the fluid substance mixture to leave the reservoir area. Therefore, the mixture flow driver can improve the fluid treatment system.

[0124] According to at least one embodiment, the fluid path system comprises an increased diameter of the mixture fluid path of the fluid path system in the non-guided flow region such that non-guided flow of the fluid substance mixture in the non-guided flow region is achieved.

[0125] According to at least one embodiment, the diameter of the mixture fluid path varies in the non-guided flow zone. It can vary so as to prevent the fluid substance mixture from contacting a wall (e.g., an inner wall of the non-guided flow zone).

[0126] According to at least one embodiment, the diameter of the mixture fluid path increases in the direction of the mixture fluid path leaving the mixing zone in the non-guided flow zone, for example increasing at least in part of the mixture fluid path and / or increasing continuously (e.g., until the reservoir zone).

[0127] According to at least one embodiment, the diameter of the mixture fluid path decreases in the direction of the mixture fluid path leaving the mixing zone in the non-guided flow zone, such as decreasing and / or continuously decreasing at least in part of the mixture fluid path.

[0128] According to at least one embodiment, the fluid treatment system includes at least one agitator for agitating the fluid material. The fluid material may be, for example, a fluid material mixture in the mixing zone.

[0129] According to at least one embodiment, at least one agitator is arranged to agitate the fluid substance mixture, for example in the reservoir region.

[0130] According to at least one embodiment, at least one stirrer is arranged in the content to be stirred.

[0131] According to at least one embodiment, the at least one stirrer is a magnetic stirrer, such as a magnetic stir bar.

[0132] According to at least one embodiment, the mixing zone has a first inlet for the first fluid substance and a second inlet for the second fluid substance.The first inlet and the second inlet may be adjacent to or coincide with outlets of the first fluid path and the second fluid path, respectively.

[0133] According to at least one embodiment, the mixing zone is formed by and / or in a mixing element, which is connected to a first conduit defining the first fluid path and / or to a second conduit defining the second fluid path.

[0134] According to at least one embodiment, the mixing element has an outlet towards the non-guided flow zone, optionally towards the guided zone or as part of the guided zone.

[0135] 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., the element comprises two first inlets or two second inlets for the first fluid substance or the second fluid substance, respectively, for example, the element comprises a first inlet for the first fluid substance and two second inlets for the second fluid substance, or the element comprises two first inlets for the first fluid substance and one second inlet for the second fluid substance). The X-shaped element may also comprise a first inlet for the first fluid substance, a second inlet for the second fluid substance and a third inlet for a third fluid substance. The mixing element may also have a psi-geometry.

[0136] According to at least one embodiment, the mixing zone is provided by a portion of a continuous conduit structure having a further portion providing a first fluid path and a second fluid path.The first and second fluid paths may be fluidly separated from each other until the mixing zone.

[0137] According to at least one embodiment, the structural element guiding the first fluid, the second fluid and / or the fluid substance mixture can be made of plastic or non-plastic material, or include plastic or non-plastic material.For example, the conduit structure for the first fluid path, the second fluid path and / or the mixed zone can be made of plastic or include plastic, such as medical grade plastic and / or polypropylene or polyvinylidene fluoride (PVDF), or made of non-plastic material or include non-plastic material, such as medical grade material such as stainless steel.And the other elements of the fluid treatment system can be made of these materials or include these materials (for example, the non-guided flow zone or the guide zone or the mixed component).

[0138] According to at least one embodiment, the fluid handling system is configured such that turbulent mixing of the first fluid substance and the second fluid substance is provided in the mixing zone.

[0139] In another aspect, the present invention relates to a method for treating a fluid, comprising: Directing a first fluid substance and a second fluid substance (e.g., as described above) within a fluid path system to a mixing zone to form a fluid substance mixture, and preventing the fluid substance mixture from contacting a wall (e.g., an interior wall) of the fluid path system in a non-directed flow zone along a flow direction of the fluid substance mixture downstream of the mixing zone for a predetermined period of time. According to at least one embodiment, the method includes directing a third fluid substance within the fluid path system to the mixing zone to form the fluid substance mixture.

[0140] According to at least one embodiment, the predetermined time period is less than or equal to one of: 1s, 950ms, 900ms, 850ms, 800ms, 750ms, 700ms, 650ms, 600ms, 550ms, 500ms, 450ms, 400ms.

[0141] According to at least one embodiment, the predetermined time period is greater than or equal to one of: 1 ms, 5 ms, 10 ms, 20 ms, 25 ms, 50 ms, 100 ms, 150 ms, 200 ms, 300 ms.

[0142] According to at least one embodiment, 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 the first fluid substance and the second fluid substance.

[0143] According to at least one embodiment, the intermediate state is a temporary state, such as a state that exists only for less than a predetermined time period. The time period can substantially correspond to a predetermined time period that prevents the fluid substance mixture from contacting a wall (e.g., inner wall) of the non-guided flow zone, or can be shorter than this predetermined time period.

[0144] According to at least one embodiment, directing the first fluid substance to the mixing zone includes directing the first fluid substance through a first fluid path of the fluid path system.

[0145] According to at least one embodiment, directing the second fluid substance to the mixing zone includes directing the second fluid substance through a second fluid path of the fluid path system.

[0146] According to at least one embodiment, directing the third fluid substance to the mixing zone includes directing the third fluid substance through a third fluid path of the fluid path system.

[0147] According to at least one embodiment, the method further comprises the step of directing the fluid substance mixture through a guide zone located downstream of the mixing zone to direct the fluid substance mixture to the non-guided flow zone.

[0148] According to at least one embodiment, the method further comprises the step of guiding the fluid substance mixture within a fluid guiding element of a fluid path system located downstream of the non-guided flow area, and / or the step of receiving the fluid substance mixture within a fluid retaining element (e.g., the reservoir area) of the fluid path system located downstream of the non-guided flow area.

[0149] According to at least one embodiment, the method further comprises the step of directing the first fluid and the second fluid simultaneously to the mixing zone.

[0150] According to at least one embodiment, the method further comprises the step of driving fluid flow of the first fluid with a first flow actuator, such as a pump, such as a syringe pump, peristaltic pump, pressurized container and / or piston pump.

[0151] According to at least one embodiment, the method further comprises the step of driving the fluid flow of the second fluid with a second flow actuator, such as a pump, such as a syringe pump, a peristaltic pump, a pressurized container and / or a piston pump.

[0152] According to at least one embodiment, described method also comprises the step that described fluid substance mixture is driven to flow to non-guided flow zone downstream or leaves from non-guided flow zone with mixture flow driver, and described mixture flow driver is pump for example, as syringe pump, peristaltic pump, pressurized container and / or piston pump.When described fluid substance mixture is or has passed through non-guided flow zone and not contacted with wall (as, inwall), described fluid substance mixture can no longer be subject to the influence of described first flow driver and second flow driver.When described fluid substance mixture passes through non-guided flow zone (for example, from described reservoir area to described outlet), described mixture flow driver can allow described fluid substance mixture to be discharged.

[0153] According to at least one embodiment, the method further comprises the step of moving the fluid substance mixture through a free fall or free flow zone.The free fall or free flow zone may be a non-guided flow zone.

[0154] According to at least one embodiment, the fluid handling system is configured to operate at a flow rate and / or have a diameter of the flow path such that for a flow rate of 1 g / cm 3of water with a density of 1 cP, a viscosity of 1 cP and a temperature of 20°C, the relationship between the flow rate and the diameter of the flow path results in the flow at the mixing zone, the guide zone, the first inlet, the second inlet and / or the outlet (e.g., the outlet of the mixing zone) being characterized in that the calculated Reynolds number (Re) is greater than or equal to one of the following values: 10000, 7500, 5000, 4000, 3000, 2900, 2800, 2700, 2600, 2500.

[0155] According to at least one embodiment, the fluid handling system is configured to operate at a flow rate and / or have a diameter of the flow path such that for a flow rate of 1 g / cm 3 of water with a density of 1 cP, a viscosity of 1 cP and a temperature of 20°C, the relationship between the flow rate and the diameter of the flow path results in the flow at the mixing zone, the guide zone, the first inlet, the second inlet and / or the outlet (e.g., the outlet of the mixing zone) being characterized in that the calculated Reynolds number (Re) is greater than or equal to one of the following values: 500, 1000, 1100, 1200, 1300, 1400, 1500, 1700, 1800, 1900, 2000.

[0156] According to at least one embodiment, the fluid handling system may be operable at a flow rate greater than or equal to 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.

[0157] According to at least one embodiment, the fluid handling system may be operable at a flow rate less than or equal 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, or 200 mL / min.

[0158] According to at least one embodiment, the fluid handling system can operate at a flow rate of 100 mL / min to 1100 mL / min, such as 200 mL / min to 150 L / min, such as about 700 mL / min or 2 L / min or 5 L / min.

[0159] The operational flow rate value of the fluid treatment system may be related to the flow rate of the fluid substance mixture and / or the flow rate of the first fluid substance and / or the second fluid substance.

[0160] According to at least one embodiment, the method is implemented using the fluid path system of the present disclosure.

[0161] According to another aspect, the present disclosure relates to use of the fluid treatment system of the present disclosure for mixing a first fluid substance with a second fluid substance to provide a fluid substance mixture.

[0162] According to another aspect, the present invention relates to a fluid substance mixture obtained or obtainable by a method or use for treating a fluid as described above or further below.

[0163] According to another aspect, the present invention relates to nanoparticle compositions, such as lipid or lipid nanoparticle (LNP) compositions, such as nucleic acid LNPs, lipid complex (LPX) compositions or polyplex (PPX) compositions, such as RNA-LPX compositions, which are obtainable or obtainable by the methods or uses described above or further below. BRIEF DESCRIPTION OF THE DRAWINGS

[0164] Figure 1a shows an exemplary blockage in the system; Figure 1b A detailed view showing an exemplary blockage in the system; Figure 1c Displays size and polydispersity index values ​​for fluid material mixture products; Figure 1d The RNA content over time during conventional mixing treatment is shown; Figure 1e Shows subvisible particle amounts with larger treatment volumes for different pipe materials; Figure 2a 、 2b Two fluid handling systems are shown according to at least two different embodiments of the present disclosure; Figure 3a 、 3b 3c shows an exemplary embodiment of a fluid handling system; Figure 4 showing additional exemplary embodiments of fluid handling systems; Figure 5 shows an exemplary embodiment of a method for treating a fluid; Figure 6a shows the particle size of the fluid material mixture product at different processing volumes as determined by photon correlation spectroscopy (PCS); Figure 6b The RNA content (mg / mL) of the fluid mixture products treated with different volumes is shown; Figure 6c Shows sub-visible particle counts of fluid material mixture products for increased processing volume. DETAILED DESCRIPTION

[0165] Figure 1a A portion of a fluid handling system is shown in which two fluids have been mixed together to form a fluid substance mixture.

[0166] The figure shows the different stages during the system operation, while continuously mixing the first fluid substance and the second fluid substance and producing the fluid substance mixture. The pipe at the top shows the system state before the mixing process begins. In the figure, the material DP that increases the visible amount is deposited in the pipe 20 (in the figure, after 150 seconds of running time and 1750mL of fluid substance mixture volume, only one pipe 20 is marked).

[0167] about Figure 1b , a more detailed description of the different stages of the system is shown and explained, wherein the stages are shown at the beginning (0 seconds running time and 0 mL fluid substance mixture volume), after 1 minute (60 seconds running time and 700 mL fluid substance mixture volume) and after 3 minutes (180 seconds running time and 2 L fluid substance mixture volume).

[0168] Figure 1b Two tubes 20a, 20b are shown in which two fluid substances have been mixed together (the mixing zone, where the mixing occurs, is shown slightly to the left of the figure, but will be explained in more detail below). The two tubes represent different stages during the operating time of the system when the first and second fluid substances are continuously mixed. The top tube (not shown) shows the system state before the mixing process begins.

[0169] As shown, in tube 20a, after only one minute of run time (60 seconds) and a volume of 700 ml of fluid substance mixture, a visible amount of material DP1 can be seen in the tube (i.e., tube 20a). Thus, as the amount of deposits on the inner walls of the system increases, the fluid path guiding the fluid substance mixture may become blocked or clogged over time. After a run time of 3 minutes (180 seconds) and a volume of 2 L of fluid substance mixture, the material DP2 in the tube (i.e., tube 20b) has increased even more.

[0170] The blockage may eventually lead to a completely blocked outlet pipe 20. This will interrupt the production of the fluid substance mixture. This blockage occurs in particular when the fluid substance mixture produced by mixing two fluids has a transition state, such as an intermediate state (commonly referred to as a "viscous phase") immediately after the two fluids are mixed.

[0171] In some cases, only part of the blockage will occur due to the sediment formed being washed away. When the sediment is washed away, it may eventually be in the final product (e.g., fluid substance mixture). This is disadvantageous because this has changed the size distribution of nanoparticles (e.g., the uneven distribution of particle size) over time, causing more and more low output and more and more uneven final product (e.g., fluid substance mixture) over time. In Figure 1B, the material DP1 and DP2 seen are washed away. The sediment washed away changes the particle distribution in the described fluid substance mixture in an uneven manner. This impact is a very undesirable impact.

[0172] The fluid mixture can comprise nanoparticles, such as lipids or liposome nanoparticles (LNPs), for example nucleic acid LNPs, lipid complexes (LPXs) or polyplexes (PPXs). The nanoparticles can comprise RNA such as mRNA, for example, by lipid and / or polymer encapsulation. It has been found that fluid mixtures suitable for forming nanoparticle compositions particularly tend to exhibit a transition phase or a viscous phase.

[0173] Another problem encountered in the system may be, for example, that the particles formed have an increased size and / or the heterogeneity of the size of the formed nanoparticles increases (e.g. as indicated by an increase in the polydispersity index (PDI)) in the fluid substance mixture. This may lead to a more heterogeneous product or even to a product that is outside the set tolerances (see, e.g., Figure 1c For nucleic acid LNPs, such as RNA-LNPs, or for nucleic acid lipid complexes, such as RNA-LPX, the PDI should be below a predetermined value (e.g., 0.4 or lower or 0.3 or lower) and / or should not change significantly with increasing processing volume.

[0174] If the fluid material mixture contains RNA-LPX, the mixture produced in such a system may exhibit a reduced RNA content, in particular, the RNA concentration decreases with increasing processing volume. Therefore, some key properties of the product may change significantly with increasing processing volume of the fluid material mixture. Figure 1c and Figure 1dIt can be seen that for conventional mixing processes, which may employ T, Y or X mixing elements having an inlet pipe and a pipe for the fluid substance mixture at the outlet of the element, the particle characteristics change significantly, for example, with increasing processing volume. It is worth noting that the materials used for the elements, i.e., the pipe and the element, have no significant effect on the key properties (see, for example, Figure 1e ).

[0175] In one possible example, the first fluid substance can include buffered RNA, more specifically: 0.3 mg / mL of BNT162b2 RNA, 18 mM HEPES and EDTA, wherein pH 7 (NAOH). The second fluid substance can include liposomes, more specifically L6 liposomes, 0.6 mM DOTMA and 1.1 mm of acetic acid, approximately 550 nm average size.

[0176] However, it has been found that other fluid substances may also show an increased tendency to direct the fluid substance mixture to form deposits on the walls of the structural element, for example shortly after the first and second fluid substances have been mixed (see the summary of the description).

[0177] Figure 2a An exemplary embodiment of a fluid treatment system 100 of the present invention is shown.

[0178] The fluid handling system 100 includes a fluid path system, such as a closed fluid path system (e.g., sealed and isolated from the environment between an inlet and an outlet of the fluid path system), wherein the fluid handling system 100 includes a first fluid path 202 for guiding a first fluid substance F1 to a mixing zone 300 of the fluid path system, and a second fluid path 204 for guiding a second fluid substance F2 to the mixing zone 300.

[0179] The mixing zone 300 is arranged in fluid communication with the first fluid path 202 and the second fluid path 204, such that the first fluid substance F1 and the second fluid substance F2 can mix to form a fluid substance mixture MX in the mixing zone 300. The fluid treatment system 100 can be configured to provide turbulent mixing of the first fluid substance and the second fluid substance in the mixing zone 300.

[0180] The mixing zone 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 zone may be formed by a mixing element. Pipes may be connected to the inlet and outlet of the mixing element to guide the corresponding liquid or fluid.

[0181] The mixing element 306 (shown in dashed lines for clarity) can be connected to the first conduit 202. The first conduit 202 can define the first fluid path 202. The mixing element 306 can be connected to the second conduit 204. The second conduit 204 can define the second fluid path 204. The first conduit 202 can be inserted into the first inlet 302 of the mixing zone 300, such as the first inlet 302 of the mixing element 306. The second conduit 204 can be inserted into the second inlet 302 of the mixing zone 300, such as the second inlet 302 of the mixing element 306. The first and second fluid paths can have the same diameter (e.g., minimum, maximum, or average diameter), such as 4 cm or 5 cm.

[0182] The mixing zone 300 can be provided by a continuous portion of a conduit structure (in which case, no separate mixing component is required). The conduit structure may include additional portions that provide the first fluid path 202 and / or the second fluid path 204. The first fluid path 202 and the second fluid path 204 can be fluidically separated from each other. The first fluid path 202 and the second fluid path 204 can be fluidically separated from each other until the mixing zone 300.

[0183] In this example, the mixing element 306 is substantially T-shaped as shown by the dashed lines in the figure (i.e., the element can be a T-type mixer). Other shapes are also possible for the mixing element, such as a Y-type, an X-type, or a psi geometry. The mixing element 306 can be configured so that when the first pipe 202 and the second pipe 204 are connected to (e.g., inserted into) the mixing element 306, the first flow direction and the second flow direction define an angle. The angle can be, for example, 45° to 315°, such as 60°. The angle can be different from 180°.

[0184] However, causing the first and second fluids to collide with each other in opposite flow directions in a T-type mixer can enhance mixing in the mixing zone. The mixing component can include an outlet toward the non-guided flow zone 400. In this example, the outlet of the mixing component is part of the guided zone 500 (see below).

[0185] The structures used for the first fluid path 202, the second fluid path 204 (e.g., tubing) and / or the mixing zone 300 (and / or mixing element 306) can be made of or include plastic, such as medical-grade plastic and / or polypropylene or polyvinylidene fluoride (PVDF), or made of or include non-plastic materials, such as medical-grade materials such as stainless steel.

[0186] The fluid treatment system 100 also includes a non-guided flow zone 400. The non-guided flow zone 400 is configured to prevent the fluid substance mixture MX from contacting inner walls 402, 404 (e.g., any inner walls), and the inner walls 402, 404 are suitable for guiding the flow of the fluid substance mixture MX along the flow direction AR1 of the fluid substance mixture MX when the fluid substance mixture MX travels through the non-guided flow zone 400. In the embodiment shown, the non-guided flow zone 400 has an increased inner diameter (e.g., minimum, maximum or average diameter) in contrast to the elements adjacent to the non-guided flow zone in the upstream direction. The elements adjacent to the non-guided flow zone (e.g., the outlet of the guide zone) may have a diameter (e.g., minimum, maximum or average diameter) that is at least or less than half the inner diameter of the non-guided flow zone. The non-guided flow zone can, for example, have an inner diameter of 20 cm, while the diameter of the outlet of the guide zone can be 0.64 cm.

[0187] The non-guided flow zone 400 extends a predetermined distance, for example, only the predetermined distance. The non-guided flow zone 400 may extend a predetermined distance downstream of the mixing zone 300. The predetermined distance may be Figure 2a The distance d1 is shown. In this example, the distance d1 corresponds to the extension of the inner wall 402. The distance d1 can be, for example, 5 cm to 565 cm, such as 165 cm, 68 cm, 35 cm, 25 cm or 20 cm.

[0188] It has been found that reducing or preventing the likelihood of the fluid material mixture MX contacting the inner wall, for example immediately after or shortly after a mixing process, may be beneficial for, for example, but not limited to, the formation of RNA-LPX (see below). Therefore, providing a fluid handling system having such a non-guided flow zone provides an improved system.

[0189] exist Figure 2a In the example of FIG, the fluid guiding element 406 of the fluid treatment system 100 is located downstream of the non-guided flow zone 400 to guide the fluid substance mixture MX. Alternatively or additionally, a fluid retaining element (not shown) of the fluid treatment system 100 may be located downstream of the non-guided flow zone 400 to receive the fluid substance mixture MX.

[0190] like Figure 2a As shown, the first fluid path 202 and the second fluid path 204 may be arranged such that the first fluid substance F1 and the second fluid substance F2 may be moved into the mixing zone simultaneously.

[0191] The flow AR2 of the first fluid substance F1 in the first fluid path and / or the flow AR3 of the second fluid substance F2 in the second fluid path 204 can be driven by a corresponding first flow driver and / or a second flow driver, for example a pump, such as a diaphragm pump (see flow drivers 206 and 208). Optionally, another flow driver 708 (e.g., a pump) can be arranged downstream of the non-guided flow zone 400 so as to drive the flow of the fluid substance mixture MX after the mixture passes through the non-guided flow zone 400. Between the inlet and the outlet of the non-guided flow zone, there may be an area that is not completely filled with liquid or fluid substance mixture. Therefore, the first flow driver and the second flow driver may not be sufficient to drive the flow of the liquid substance mixture downstream of the non-guided flow zone.

[0192] like Figure 2a As shown, the fluid treatment system 100 further includes a guide zone 500. As shown, the guide zone can be arranged along the flow direction AR1 between the mixing zone 300 and the non-guided flow zone 400. The guide zone 500 can be configured to determine (e.g., set) an entry flow direction AR4 of the fluid substance mixture MX. The entry flow direction AR4 can be the flow direction of the fluid substance mixture MX entering the non-guided flow zone 400.

[0193] The guide zone 500 may be very advantageous in the case where the fluid treatment system 100 is arranged so that gravity can change the flow direction of the fluid material mixture after entering the non-guided flow zone 400. Figure 2a As shown, if the fluid material mixture flows vertically or along gravity, the guide zone may not be so favorable, but may still have a positive guiding effect on the flow entering the non-guided flow zone 400, for example, when the flow in the mixing zone 300 may be more turbulent than the flow in the non-guided flow zone 400.

[0194] In other cases, where the flow direction in the non-guided flow direction can be changed by gravity, the guide zone can define the entry flow direction of the fluid material mixture MX into the mixing zone 300. For example, the mixing zone 300 is configured to or directly guide the fluid mixture flow into the non-guided flow zone 400 in a manner so as not to contact any inner walls (see 402 and 404) during passage through the non-guided flow zone 400. The guide zone 500 can be approximately 2 cm long.

[0195] exist Figure 2aIn an exemplary embodiment of the present invention, the inlet flow direction AR4 is parallel to the main axis of the non-guided flow area and is oriented along gravity. Alternatively, the inlet flow direction AR4 can be angled relative to the main axis of the non-guided flow area 400 and / or relative to gravity (see, for example, Figure 4 , arrow AR6 relative to AR7).

[0196] like Figure 2a As shown, the fluid path of the fluid path system guiding the fluid substance mixture MX is widened (indicated by reference numerals 408a, 408b) as seen along the flow direction from the mixing zone 300 to the non-guided flow zone 400 (along the flow direction leaving the mixing zone 300), for example at the end of the guide zone 400.

[0197] For a predetermined distance d1 of the non-guided flow zone 400, the fluid treatment system 100 may include a free fall zone 600 or a free flow zone 600, which allows the fluid material mixture MX to flow through the fluid treatment system 100 without contacting the inner walls 402, 404 of the fluid treatment system 100, such as the inner walls of the non-guided flow zone 400.

[0198] The free fall zone 600 may be achieved by the geometry of the non-guided flow zone 400 and optionally by the direction of receiving the fluid substance mixture MX from the guided zone 500 .

[0199] The fluid path system defines a first flow direction AR2 for the first fluid substance F1 from the first fluid path 202 through the first inlet to the mixing zone 300. The fluid path system defines a second flow direction AR3 for the second fluid substance F2 from the second fluid path 204 through the second inlet to the mixing zone 300. The first flow direction AR2 and the second flow direction AR3 may define an angle of 120°, for example.

[0200] In this example, the non-guided flow region 400 may have an entry region 410. The entry region is the region in the non-guided flow region where the fluid substance mixture enters the non-guided flow region. The mixing region 300 may additionally or alternatively include an outlet for the fluid substance mixture. In this example, the outlet of the mixing region is 2 mm wide (not shown).

[0201] In this particular example, the inlet region 410 of the non-guided flow region is adjacent to (or coincides with) the outlet of the guided region 500 .

[0202] In this example, the non-guided flow zone 400 may be 35 cm long. The non-guided flow zone 400 may be selected so that during operation of the fluid treatment system 100, the fluid material mixture MX may come into contact with, or be prevented from contacting, the inner walls 402, 404 of the non-guided flow zone 400 for a predetermined period of time, such as 5 ms. The extent of the non-guided flow zone may be selected so that, at a given flow rate, there is sufficient time for the material mixture to assume its stable state or at least significantly reduce its tendency to form deposits on the inner walls.

[0203] The fluid handling system 100 is also configured to operate at a flow rate and / or have a diameter (e.g., minimum, maximum, or average diameter) of the flow path such that for a flow rate of 1 g / cm 3 For water with a density of 1 cP, a viscosity of 1 cP and a temperature of 20°C, the relationship between the flow rate and the diameter of the flow path results in the flow at the mixing zone 300, the guide zone 500, the first inlet, the second inlet and / or the outlet (e.g., the outlet of the mixing zone) being characterized by a calculated Reynolds number (Re) of 1100.

[0204] The first fluid substance F1 and the second fluid substance F2 are selected so that the fluid substance mixture MX resulting from mixing the first fluid substance F1 and the second fluid substance F2 has an intermediate state, such as a temporary state or a transitional state. The intermediate state may occur, for example, during and / or immediately after mixing the first fluid substance F1 and the second fluid substance F2.

[0205] In the embodiment of the present invention, the intermediate state can only exist and be less than the predetermined time period.After the intermediate state, the fluid substance mixture MX can present stable state.The fluid substance mixture is in the intermediate state and is more inclined to form sediment on the wall (as, the inwall that defines fluid path) than being in stable state.The example of the trend of this formation sediment and the related problem of pipeline obstruction is shown in Fig. 1, and the exemplary obstruction of system is described.

[0206] The flow treatment system 100 is configured and / or operated such that the fluid substance mixture MX flows in its intermediate state only in the mixing zone 300 and / or the non-guided flow zone 400 and / or optionally the guided zone 500 .

[0207] The first fluid material F1 and the second fluid material F2 can be selected to form a fluid material mixture MX comprising a colloid. When the two are mixed together, the colloid can have an average particle size greater than or equal to 10 nm or less than or equal to 1000 nm, for example, 200 to 500 nm, such as about 400 nm. The size of the particles (for example, for nucleic acids LPX, such as RNA-LPX) can depend on the size of the lipid-encapsulated structure. Thus, smaller or larger diameters or particle sizes can occur.

[0208] The first fluid substance F1 can contain RNA, for example, it can be an RNA solution. The second fluid substance F2 can include liposomes or lipid complexes. One or both of substances F1 and F2 can be buffered. When the substances are mixed, RNA-LPX or RNA-LNP can be formed.

[0209] Described first fluid substance and second fluid substance F1 and F2 can be for example ionic species, as positively charged ion or negatively charged ion substance or positively charged ion and negatively charged ion substance.Described first fluid substance and / or second fluid substance mixture can be for example ionizable substance.Described first fluid substance F1 and described second fluid substance F2 can be different from each other, for example, described first fluid substance F1 is negatively charged ion substance, and described second fluid substance F2 is cationic species.

[0210] The first fluid substance F1 may include a polymeric substance, such as a polymeric ionic substance. The first fluid substance F1 may include nucleic acid, peptide or protein.

[0211] The second fluid substance F2 can be a colloidal suspension, for example an ionic colloidal suspension, such as a cationic colloidal suspension. The second fluid substance F2 can comprise hydrophilic and / or lipophilic substances, for example amphipathic substances. The second fluid substance F2 can comprise lipid. The second fluid substance can comprise a cationic polymer.

[0212] The second fluid substance F2 may comprise at least one lipid selected from the group consisting of: (i) an ionizable lipid, preferably an ionizable cationic lipid, for example an ionizable cationic amino lipid, such as ALC-0315 ((4-hydroxybutyl)azadiyl)bis(hexane-6,1-diyl)bis(2-hexyldecanoate)), or SM-102 (heptadecan-9-yl 8-((2-hydroxyethyl)(6-oxo-6-(undecyloxy)hexyl)amino)octanoic acid), or DOPE (1,2-dioleoyl-sn-3-phosphatidylethanolamine), or DOTMA (N-(2,3-dioleoyloxy)propyl)N,N,N-trimethylammonium chloride), or DOSPA (N-(1-(2,3-dioleoyloxy)propyl)-N-(2-(sperminecarboxamido)ethyl)-N,N-dimethylammonium trifluoroacetate); (ii) non-cationic helper lipids or phospholipids, for example, neutral lipids such as DSPC (1,2-distearoyl-17-glycero-3-phosphocholine) or analogs or substitutes thereof; (iii) sterols or other structured lipids, such as cholesterol; and (iv) PEG lipids, such as 1,2-dimyristoyl-sn-glyceromethoxypolyethylene glycol (PEG-DMG). Other lipids may also be suitable for inclusion in the second fluid. Additional alternatives to PEG lipids may include, but are not limited to: polysarcosine, polyoxazoline, uncharged lipids such as pSar or pMeOx.

[0213] Said first fluid substance and said second fluid substance can all be colloidal suspensions, for example ionic colloidal suspensions.Said first fluid substance can be or can comprise the amphipathic substances of polymerization or the lipophilic substance of polymerization or the hydrophilic substance of polymerization.The second fluid substance can comprise the amphipathic substances of amphipathic or polymerization or the lipophilic substance of polymerization or the hydrophilic substance of polymerization.

[0214] In some embodiments, the first fluid substance and the second fluid substance can be pharmaceutical substances, for example biopharmaceutical substances. At least one or both of the first fluid substance and the second fluid substance can be aqueous compositions, for example 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 aqueous compositions, for example aqueous solutions or aqueous dispersions, and the second fluid substance can be an organic composition, for example organic solution or dispersions. The organic composition can comprise an organic solvent, for example, greater than 1%, 10%, 25%, 50%.

[0215] One or both of the first fluid substance and the second fluid substance may be a medical fluid substance.

[0216] All of the above-described combinations of first fluid substances F1 and second fluid substances F2 may tend to exhibit an intermediate state (eg, a viscous phase) when mixed together to form a fluid substance mixture MX. The advantages described with respect to the system of the present invention apply to all of these fluids.

[0217] For all mixtures of charged polymers / lipids, this intermediate state, such as viscosity, will occur. For all mixtures of charged molecules, the sedimentation of the material in the mixed zone begins to experience layer-by-layer deposition. During the mixed phase, a viscous and colloidally unstable intermediate is formed until one of the two fluid substances is fully saturated with another fluid substance (e.g., the first fluid substance or the second fluid substance), resulting in the stabilization / passivation of nanoparticles.

[0218] For LNPs with an N / P ratio (i.e., the ratio of positively charged polymer amine (N = nitrogen) groups to negatively charged nucleic acid phosphate (P) groups) greater than 1, this process may occur on a different timescale, as the LNPs are most likely formed from lipids in ethanolic solution or from micellar intermediate structures with lipid excess, although the characteristics of the liposomes used in the LPX method that affect the particle size distribution and the rearrangement of pre-existing structures may be responsible for this intermediate unstable state.

[0219] In one possible example, the first fluid material can include buffered RNA, more specifically: 0.3 mg / mL BNT162b2 RNA in 18 mM HEPES and EDTA, wherein pH 7 (NAOH). The second fluid material can include liposomes, more specifically L6 liposomes, in 0.6 mM DOTMA and 1.1 mm acetic acid, about 550 nm mean size.

[0220] like Figure 2a As shown, the first fluid path 202 is fluidically connected or fluidically connectable to a first reservoir 602. The first reservoir 602 may include the first fluid substance F1. The first fluid substance F1 may be driven from the first reservoir 602 to the mixing zone 300 via the first fluid path 202. The second fluid path 204 may be fluidically connected or fluidically connectable to a second reservoir 604. The second reservoir may include a second fluid substance F2, such that the second fluid substance F2 may be driven from the second reservoir 604 to the mixing zone 300 via the second fluid path 204.

[0221] The fluid treatment system 100 may further include a reservoir area 700 (e.g., a container, such as a bag) for collecting the fluid substance mixture MX. The reservoir area may have a capacity of 10 L. The reservoir area 700 may be arranged downstream of the non-guided flow area 400 as seen along the flow direction AR1 of the fluid treatment system 100. The fluid substance mixture MX in the reservoir area 700 forms a surface 702. The surface 702 may, for example, define the reservoir area 700 on the side facing the non-guided flow area 400 as seen in the direction opposite to the flow direction AR1 of the fluid substance mixture MX to the reservoir area 700. After flowing through the non-guided flow area 400, the fluid substance mixture MX may enter the reservoir area 700. The fluid substance mixture MX may enter the reservoir area 700 via the surface 702, for example, in the form of droplets 704 impacting a surface.

[0222] The fluid handling system 100 may further include a reservoir area outlet 706. The reservoir area outlet 706 may be in fluid communication with the reservoir area 700. The reservoir area outlet 706 may be provided to remove contents from the reservoir area 700, such as the fluid substance mixture MX.

[0223] A mixture flow driver 708 may be operably connected to the reservoir area, for example, to the reservoir area outlet 706. The mixture flow driver 708 may be configured to provide (eg, draw) the fluid substance mixture MX out of the reservoir area 700.

[0224] The reservoir area 700 may be included in the fluid path system. The reservoir area may be directly connected to the non-guided flow area 400. The reservoir area may be an area in the fluid path system that is downstream of the non-guided flow area and immediately adjacent to the non-guided flow area.

[0225] One or more additional fluid substances may be added to the mixture in the reservoir region (eg, container) downstream of the non-directed flow region 400 and / or in the container 700 through ports (not explicitly shown).

[0226] The fluid substance mixture MX can be continuously withdrawn from the reservoir region 700, for example, downstream of the non-guided flow region 400 via a flow driver 708. The fluid substance mixture can be.

[0227] The fluid processing system 100 may further include an agitator, such as a magnetic agitator. The agitator may be arranged in the contents to be stirred to stir the fluid material. The agitator may be arranged in the reservoir area to stir, for example, a fluid material mixture MX (not shown) in the reservoir area.

[0228] Figure 2b Various exemplary embodiments of a fluid treatment system 100 are shown. Figure 2b The fluid handling system 100 is substantially similar to Figure 2a The fluid treatment system 100 is described. Like reference numerals refer to like elements. Figure 2b The fluid handling system 100 is relative to Figure 2a The fluid handling system 100 is different.

[0229] Figure 2b The fluid treatment system 100 in the embodiment of FIG is an example of an interruption system. Specifically, the non-guided flow zone 400 can be physically disconnected from the mixing zone 300. The non-guided flow zone 400 can also be physically disconnected from the guide zone 500. The fluid material mixture MX flowing downstream from the guide zone 500 experiences free fall for a predetermined period of time and a predetermined distance, and the fluid material mixture MX does not contact the walls 402, 404 of the non-guided flow zone within the predetermined distance.

[0230] Figure 3a , Figure 3b and Figure 3c Shown Figure 2a and Figure 2b Other exemplary embodiments of the fluid treatment system 100 are described. Figure 3a and Figure 3b The difference between the various embodiments is the shape of the non-guided flow region 400. Additionally, Figure 3c The fluid handling system shown includes non-guided flow zones of different shapes and mixing zones 300 and / or guided zones 500 of different shapes.

[0231] exist Figure 3a and Figure 3b In the embodiment of the present invention, the diameter of the mixture flow path in the non-guided flow region 400 is varied. Figure 3a In the embodiment, the diameter of at least a portion of the mixture fluid path increases in a direction away from the mixing zone 300 in the non-guided flow zone 400 , for example, in a fluid mixture flow direction AR4 away from the guide zone 500 .

[0232] exist Figure 3b In the embodiment, the diameter of the mixture flow path decreases in a direction away from the mixing zone 300 in the non-guided flow region 400, at least in a portion of the mixture flow path.

[0233] Figure 3c An exemplary embodiment of a fluid handling system 100 is shown that includes two inlets, such as two second inlets 304a, 304b for a second fluid substance F2, and one inlet for a first fluid substance F1, such as one first inlet 302. The mixing zone 300 may have an X shape or a psi geometry.

[0234] In an additional or alternative example, the inlet 304b may be a third inlet 304b for a third fluid substance (eg, a gas such as air) in a third fluid path.

[0235] The diameter of the mixture flow path in the non-guided flow region 400 first increases and then decreases in a direction away from the mixing region 300, at least in a portion of the mixture flow path.

[0236] Figure 4 Another exemplary embodiment of the fluid treatment system 100 is shown. In this example, the first fluid path 202, the second fluid path 204, the mixing zone 300, and the guide zone 500 are generally tilted clockwise, for example, by approximately 20 degrees, relative to the embodiments in the previous figures. The outlet of the guide zone 500 can be tilted, for example, by 20 degrees counterclockwise or clockwise. Each element can be independently arranged in an inclined or non-inclined position. The angle of element tilt can vary for each element or only for some elements.

[0237] In this embodiment, the inlet flow direction AR6 is angled relative to a major axis AR7 of the non-guided flow region 400. The major axis may be oriented along the direction of gravity.

[0238] In embodiments such as these, where the outlets of the mixing zone and / or guide zone are not oriented directly downward but are angled relative to the primary downstream direction, the non-guided flow zone may be adapted to ensure non-guided flow of the fluid material mixture, such as flow of the fluid material mixture without contacting the inner walls 402 and 404 of the non-guided flow zone 400 for a predetermined period of time.

[0239] Once the guided area is passed in the non-guided flow area or shortly before the non-guided flow area, the direction change of the fluid substance mixture is obtained by gravity. Figure 4 (shown by a curved arrow and reference numeral MX).

[0240] In this embodiment, for example, the inner wall 402 of the non-guided flow area can be configured in such a manner as to ensure that the fluid substance mixture MX leaving the guide area 500 does not contact the inner wall 402 within a predetermined period of time and / or a predetermined distance d2. The inner wall 402 can be configured to have a Figure 4 The concave shape of the example (seen from the inside). The distance d2 can be Figure 2a The distance d1 is consistent.

[0241] The distance d2 may be 5 cm to 565 cm, for example, 165 cm, 68 cm, 35 cm, 25 cm or 20 cm.

[0242] Figure 5 A schematic diagram of an exemplary embodiment of a method for treating a fluid is shown. Mail items in the method may be represented by the same reference numerals used to describe the fluid treatment system. However, the method is not limited to application to the fluid treatment system 100 of the preceding figures.

[0243] In the first step S1 of the method, a first fluid substance F1 and a second fluid substance F2 within a fluid path system are directed to a mixing zone 300 to form a fluid substance mixture MX. Specifically, directing the first fluid substance F1 to the mixing zone 300 may include directing the first fluid substance F1 through a first fluid path of the fluid path system. Directing the second fluid substance F2 to the mixing zone 300 may include directing the second fluid substance F2 through a second fluid path of the fluid path system.

[0244] The first fluid substance F1 and the second fluid substance F2 may be simultaneously introduced into the mixing zone 300. The fluid flow of the first fluid substance F1 and / or the second fluid substance F2 (eg, to the mixing zone 300) may be achieved by a first flow driver and / or a second flow driver, respectively.

[0245] The first flow drive and / or the second flow drive can be, for example, a peristaltic pump. Alternatively, the first flow drive can be different from the second flow drive. For example, the first flow drive can be a syringe pump and the second flow drive can be a diaphragm pump, or vice versa.

[0246] The first fluid substance F1 and the second fluid substance F2 can be selected so 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 can occur during and / or immediately after the mixing of the first fluid substance F1 and the second fluid substance F2. The intermediate state of the fluid substance mixture MX may only be a temporary state.

[0247] The first fluid substance F1 and the second fluid substance F2 may be directed through the mixing zone 300 for a period of, for example, 40 ms to form a fluid substance mixture MX.

[0248] In an optional step not shown, the method includes directing a third fluid substance within the fluid path system to the mixing zone to form a fluid substance mixture. Directing the third fluid substance to the mixing zone may include directing the third fluid substance through a third fluid path of the fluid path system.

[0249] In a second step S2 of the exemplary method, contact between the fluid substance mixture MX and the walls 402, 404 of the fluid path system is prevented for a predetermined period of time. This may occur in the non-guided flow region 400, with the fluid substance mixture Mx flowing in the direction AR2 downstream of the mixing region 300.

[0250] The fluid substance mixture MX may have the intermediate state only for less than the predetermined period of time (eg, the predetermined period of time during which the fluid substance mixture MX is prevented from contacting the walls 402 , 404 of the fluid path system).

[0251] The method may further comprise the step of guiding the fluid substance mixture MX through a free-falling zone or a free-flowing zone. For example, the free-falling zone or the free-flowing zone may be a non-guided flow zone 300 or in a non-guided flow zone 300.

[0252] Before the second step S2, the fluid substance mixture MX may be guided through a guide zone 500 located downstream of the mixing zone 300. Guiding the fluid substance mixture MX through the guide zone 500 may guide the fluid substance mixture MX to the non-guided flow zone 300.

[0253] The exemplary method may further include directing the fluid substance mixture MX within a fluid directing element of a fluid path system downstream of the non-guided flow zone 300. Additionally or alternatively, the fluid substance mixture MX may be received in a fluid retaining element 700 of the fluid path system downstream of the non-guided flow zone 300.

[0254] Guiding the fluid substance mixture MX within a flow guiding element of a fluid path system downstream of the non-guided flow zone 300 can be achieved, for example, by means of a further mixture flow actuator, such as a pump, eg a piston pump.

[0255] The fluid handling system 100 may be configured to operate at a flow rate and / or have a flow path diameter such that for a flow rate of 1 g / cm 3For water with a density of 1 cP, a viscosity of 1 cP and a temperature of 20°C, the relationship between the flow rate and the diameter of the flow path results in the flow at the mixing zone 300, the guide zone 500, the first inlet, the second inlet and / or the outlet (e.g., the outlet of the mixing zone) being characterized by a calculated Reynolds number (Re) of 1100.

[0256] The described exemplary methods may be implemented using any of the fluid path systems described in the above embodiments.

[0257] The fluid handling system may, for example, be used to mix a first fluid substance F1 with a second fluid substance F2 to provide a fluid substance mixture MX.

[0258] Figures 6a to 6c The beneficial effects of the fluid treatment system of the present disclosure on the provided fluid substance mixture product are shown.

[0259] Figure 6a The graph shows that the particle size, as measured by photon correlation spectroscopy (PCS), in a fluid material mixture treated in a fluid treatment system according to any embodiment of the present disclosure, and optionally in a fluid material mixture treated according to a method according to any embodiment of the present disclosure, remains constant in diameter (in nm) even when the treatment volume is increased. In the legend, "no T-piece" indicates that a free-fall zone is provided, such as when using a fluid treatment system having a free-fall zone according to the present disclosure.

[0260] It can be seen that a constant particle size (eg, average diameter) of approximately 400 nm can be achieved using the fluid handling system of the present invention.

[0261] Figure 6b The graph in shows that if the fluid substance mixture contains RNA, the RNA content, ie the RNA concentration (mg / mL), remains essentially constant as the processing volume increases.

[0262] These results demonstrate that the fluid processing system of the present disclosure can be utilized to achieve constant product quality for the fluid material mixture, even with varying processing volumes.

[0263] Figure 6c The amount of subvisible particles in the fluid material mixture product produced at different stages (e.g., F01 to F20) at a pump speed of 200 mL / min (e.g., a first fluid path and a second fluid path each having a processing volume of 100 mL / min) is shown. As shown, the amount of subvisible particles (byproducts) in the micrometer size range remains stable over time and is significantly lower than in conventional processes (e.g., syringe pumps) labeled C1, C2, and C3.

[0264] Compared to solutions without non-guided flow areas (see Figures 1a to 1e ) showed significant improvements. In particular, the number of byproducts, such as subvisible particles (SVPs), was reduced compared to conventional treatments. Furthermore, the number of SVPs did not increase over time (as is evident with conventional methods).

[0265] Further experimental results also showed that there were no quality-related changes or trends indicating a significant decrease in the quality of the fluid mixture product, for example, the volume ratio of the first fluid material (e.g., RNA) and the second fluid material (e.g., liposomes) relative to subvisible particles (SVP) changed by up to 25%.

[0266] We note that features disclosed in the introductory part of the specification also apply to the description of the exemplary embodiments, even if they are not explicitly repeated.

[0267] Without limiting the present disclosure, the following describes several embodiments or clauses of the present invention for illustrative purposes. These clauses are not claims but may be the subject of claims.

[0268] Clause 1: A fluid handling system comprising: A fluid path system, the fluid path system comprising: a first fluid path directing a first fluid substance toward a mixing zone of the fluid path system, a second fluid path directing a second fluid substance toward the mixing zone, wherein the mixing zone is arranged in fluid communication with the first fluid path and the second fluid path, such that the first fluid substance and the second fluid substance can be mixed in the mixing zone to form a fluid substance mixture, The fluid handling system includes a non-guided flow zone, wherein the non-guided flow zone is configured so that when the fluid substance mixture flows through the non-guided flow zone, the fluid substance mixture can contact or be prevented from contacting an inner wall suitable for guiding the fluid substance mixture to flow along the flow direction of the fluid substance mixture, and wherein the non-guided flow zone extends a predetermined distance downstream of the mixing zone, for example, only extends the predetermined distance.

[0269] Clause 2: The fluid treatment system of clause 1, wherein a fluid directing element or a fluid retaining element of the fluid treatment system is located downstream of the non-directed flow zone to receive and / or direct the fluid substance mixture.

[0270] Clause 3: The fluid treatment system of any preceding clause, wherein the fluid treatment system is configured such that the first fluid substance and the second fluid substance can be moved to the mixing zone simultaneously.

[0271] Item 4: A fluid handling system as described in any of the preceding items, wherein the diameter of the first fluid path (e.g., the maximum, minimum or average diameter) and / or the diameter of the second fluid path (e.g., the maximum, minimum or average diameter) is greater than or equal to 0.5 mm and / or less than or equal to 55 mm.

[0272] Item 5: A fluid handling system as described in any of the preceding items, wherein the fluid flow of the first fluid substance along the first fluid path is drivable or driven by a first flow drive, the first flow drive being for example a pump, such as a syringe pump, a peristaltic pump, a diaphragm pump and / or a piston pump, or a pressurized container.

[0273] Item 6: A fluid handling system as described in any of the preceding items, wherein the fluid flow of the second fluid substance along the second fluid path is drivable or driven by a second flow drive, the second flow drive being, for example, a pump, such as a syringe pump, a peristaltic pump, a diaphragm pump and / or a piston pump, or a pressurized container.

[0274] Item 7: A fluid handling system as described in any of the preceding items, wherein the fluid flow of the fluid material mixture downstream of the non-guided flow zone is driveable by or driven by a mixture flow drive, the mixture flow drive being for example a pump, such as a syringe pump, peristaltic pump, diaphragm pump and / or piston pump, or a pressurized container.

[0275] Item 8: A fluid processing system as described in any of the preceding items, wherein the fluid path system includes a guide zone, which can be arranged between a mixing zone and a non-guided flow zone along the flow direction of the fluid substance mixture, wherein the guide zone can be configured to determine the entry flow direction of the fluid substance mixture, and the fluid substance mixture enters the non-guided flow zone in this direction.

[0276] Clause 9: A fluid handling system as described in any of the preceding clauses, wherein the guide area has a length less than or equal to one of the following values: 5 cm, 4 cm, 3.5 cm, 3 cm, 2.5 cm, 2 cm, 1.5 cm, 1 cm, 0.5 cm, 0.4 cm, 0.3 cm, 0.2 cm.

[0277] Clause 10: The fluid treatment system of Clause 8 or 9, wherein the guide zone has a length greater than or equal to one of the following values: 0.05 cm, 0.1 cm, 0.2 cm, 0.5 cm, 1 cm, 1.5 cm, 2 cm.

[0278] Clause 11: The fluid treatment system of any one of clauses 8 to 10, wherein the incoming flow direction is parallel to a major axis of the non-guided flow zone.

[0279] Clause 12: The fluid treatment system of any of Clauses 8 to 10, wherein the incoming flow direction is angled relative to a major axis of the non-directed flow zone.

[0280] Item 13: A fluid handling system as described in any of items 8 to 12, wherein the fluid path of the fluid path system guiding the fluid material mixture widens as seen along the flow direction from the mixing zone to the non-guided flow zone (along the flow direction away from the mixing zone), for example at the end of the guide zone.

[0281] Item 14: A fluid handling system as described in any of the preceding items, wherein for a predetermined distance, for example due to an interruption of the fluid path system in a non-guided fluid area and / or due to the mixture fluid path of the fluid path system in the non-guided fluid area being configured to have an appropriate width, the fluid handling system has a free fall area or a free flow area, and the free fall area or the free flow area can allow the fluid substance mixture to flow through the fluid handling system without contacting the inner wall of the fluid handling system, for example the inner wall closest to the fluid substance mixture.

[0282] Clause 15: A fluid treatment system as described in any of the preceding clauses, wherein the fluid path system defines a flow direction of the first fluid substance from the first fluid path through the first inlet to the mixing zone, and the fluid path system defines a flow direction of the second fluid substance from the second fluid path through the second inlet to the mixing zone. The first flow direction and the second flow direction may define an angle. The angle may be in the range of 45° to 315°, such as in the range of 60° to 300°, such as 120° to 270° or approximately 180°.

[0283] Clause 16: The fluid treatment system of any preceding clause, wherein the mixing zone has an inlet for the first fluid substance and / or wherein the non-directed flow zone comprises an entry zone.

[0284] Clause 17: The fluid treatment system of Clause 16, wherein the inner diameter (eg, minimum, maximum, or average diameter) of the outlet or the inlet zone is greater than or equal to 0.5 mm and less than or equal to 6 cm, eg, 1 mm to 5.2 cm.

[0285] Clause 18: The fluid treatment system of clause 16 or 17 as additionally referenced to clause 8 or any clause dependent thereon, wherein the entry region of the non-guided flow zone is adjacent to or coincides with the outlet of the guided region.

[0286] Clause 19: A fluid handling system as described in any of the preceding clauses, wherein the predetermined distance is greater than or equal to one of the following values: 5cm, 6cm, 7cm, 8cm, 9cm, 10cm, 11cm, 12cm, 13cm, 20cm, 35cm, 50cm, 80cm, 100cm, 200cm.

[0287] Clause 20: A fluid handling system as described in any preceding clause, wherein the predetermined distance is less than or equal to one of the following values: 600cm, 565cm, 550cm, 500cm, 450cm, 400cm, 300cm, 200cm, 165cm, 68cm, 35cm, 30cm, 25cm, 20cm, 15cm, 13cm.

[0288] Clause 21: The fluid treatment system of any preceding clause, wherein the predetermined distance is selected such that the fluid substance mixture is able to contact or is prevented from contacting the inner wall for a predetermined period of time, such as during operation of the fluid treatment system.

[0289] Clause 22: The fluid treatment system of clause 21, wherein the predetermined time period is less than or equal to one of: 1 s, 950 ms, 900 ms, 850 ms, 800 ms, 750 ms, 700 ms, 650 ms, 600 ms, 550 ms, 500 ms, 450 ms, 400 ms.

[0290] Clause 23: The fluid treatment system of clause 21 or 22, wherein the predetermined time period is greater than or equal to one of: 1 ms, 5 ms, 10 ms, 20 ms, 25 ms, 50 ms, 100 ms, 150 ms, 200 ms, 300 ms.

[0291] Clause 24: The fluid treatment system of any preceding clause, wherein the fluid treatment system is configured to operate at a flow rate and / or have a diameter (e.g., minimum, maximum, or average diameter) of the flow path such that for a flow rate of 1 g / cm 3 of water with a density of 1 cP, a viscosity of 1 cP and a temperature of 20°C, the relationship between the flow rate and the diameter of the flow path results in the flow at the mixing zone, the guide zone, the first inlet, the second inlet and / or the outlet (e.g., the outlet of the mixing zone) being characterized in that the calculated Reynolds number (Re) is greater than or equal to one of the following values: 500, 1000, 1100, 1200, 1300, 1400, 1500, 1700, 1800, 1900, 2000.

[0292] Clause 25: The fluid treatment system of any preceding clause, wherein the fluid treatment system is configured to operate at a flow rate and / or have a diameter (e.g., minimum, maximum, or average diameter) of the flow path such that for a flow rate of 1 g / cm 3 of water with a density of 1 cP, a viscosity of 1 cP and a temperature of 20°C, the relationship between the flow rate and the diameter of the flow path results in the flow at the mixing zone, the guide zone, the first inlet, the second inlet and / or the outlet (e.g., the outlet of the mixing zone) being characterized in that the calculated Reynolds number (Re) is less than or equal to one of the following values: 10000, 7500, 5000, 4000, 3000, 2900, 2800, 2700, 2600, 2500.

[0293] Item 26: A fluid handling system as described in Item 24 or 25, wherein the fluid handling system is capable of handling or providing a fluid flow, wherein the fluid flow (e.g., in the mixing zone, the guide zone, the first inlet, the second inlet and / or the outlet) has a Reynolds number (Re) of 500 to 10,000, for example, 500 to 3,000, such as 1,700 to 2,500.

[0294] Clause 27: A fluid handling system as described in any of the preceding clauses, wherein the first fluid substance and the second fluid substance are selected so that the fluid substance mixture produced by mixing the first fluid substance and the second fluid substance has an intermediate state, for example during and / or immediately after mixing the first fluid substance and the second fluid substance.

[0295] Clause 28: The fluid treatment system of Clause 27, wherein the intermediate state is a transient state, eg, a state that exists for less than a predetermined period of time.

[0296] Clause 29: The fluid treatment system of clause 27 or 28, wherein after the intermediate state, the fluid substance mixture exhibits a steady state.

[0297] Clause 30: The fluid treatment system of clauses 27 to 29, wherein the fluid substance mixture is more prone to forming deposits on walls, such as interior walls defining a fluid path, in its intermediate state than in its stable state.

[0298] Clause 31: The fluid treatment system of clauses 27 to 30, wherein the fluid treatment system is configured such that the fluid substance mixture flows in the non-guided flow zone in its intermediate state.

[0299] Clause 32: A fluid handling system as described in 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 in the mixing zone and / or the non-guided flow zone and / or optionally the guided zone.

[0300] Clause 33: A fluid processing system as described in any of the preceding clauses, wherein the first fluid substance and the second fluid substance are selected to form a fluid substance mixture containing colloids, for example, the colloids have an average particle size greater than or equal to 10nm and / or less than or equal to 100nm.

[0301] Clause 34: The fluid treatment system of any preceding clause, wherein the first fluid species comprises ionic species and / or ionizable species.

[0302] Clause 35: The fluid treatment system of any preceding clause, wherein the second fluid species comprises ionic species and / or ionizable species.

[0303] Item 36: A fluid treatment system as described in item 34 or 35, wherein the ionic species and / or ionizable species are cationic species or anionic species or cationic and anionic species, such as zwitterionic species, and / or cationic ionizable species or anionic ionizable species or cationic and anionic ionizable species, such as zwitterionic ionizable species.

[0304] Clause 37: The fluid treatment system of any of clauses 34 to 36, wherein the ionic species of the first fluid species are anionic species and the ionic species of the second fluid species are cationic species.

[0305] Clause 38: The fluid treatment system of any of clauses 34 to 37, wherein the first fluid species comprises a polymeric species, such as a polymeric ionic species.

[0306] Clause 39: The fluid treatment system of any one of clauses 34 to 38, wherein the first fluid substance comprises a nucleic acid, a peptide, or a protein.

[0307] Clause 40: The fluid treatment system of any one of clauses 34 to 39, wherein the first fluid substance comprises RNA, wherein optionally, the first fluid substance is RNA, such as an mRNA solution.

[0308] Clause 41: The fluid treatment system of any preceding clause, wherein the second fluid substance is a colloidal suspension, such as an ionic colloidal suspension, such as a cationic colloidal suspension.

[0309] Clause 42: The fluid treatment system of any preceding clause, wherein the second fluid substance comprises a hydrophilic and / or lipophilic substance, such as an amphiphilic substance.

[0310] Clause 43: The fluid treatment system of any preceding clause, wherein the second fluid substance comprises at least one lipid, Clause 44: The fluid treatment system of any preceding clause, wherein the second fluid substance comprises liposomes. Clause 45: The fluid treatment system of any preceding clause, wherein the second fluid substance comprises a cationic polymer.

[0311] Clause 46: The fluid treatment system of clauses 1 to 45, wherein the first fluid substance and the second fluid substance are both colloidal suspensions, such as ionic colloidal suspensions.

[0312] Clause 47: A fluid handling system as described in any of the preceding clauses, wherein the first fluid 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 or polymeric amphiphilic substance or a polymeric lipophilic substance or a polymeric hydrophilic substance.

[0313] Clause 48: The fluid treatment system of any preceding clause, wherein the first fluid substance and / or the second fluid substance is buffered.

[0314] Clause 49: The fluid processing system of any preceding clause, wherein one of the first and second fluid substances or the fluid substance mixture is a biopharmaceutical substance.

[0315] Item 50: A fluid processing system as described in any of the preceding items, 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 of the first fluid substance and the second fluid substance are aqueous compositions, such as aqueous solutions or aqueous dispersions.

[0316] Clause 51: The fluid treatment system of any preceding clause, wherein at least one or both of the first fluid substance and the second fluid substance is a solution.

[0317] Clause 52: The fluid treatment system of any preceding clause, wherein at least one or both of the first fluid substance and the second fluid substance are dispersions.

[0318] Clause 53: The fluid treatment system of any preceding clause, 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.

[0319] Clause 54: The fluid treatment system of Clause 53, wherein the organic composition is an organic solution or dispersion.

[0320] Clause 55: The fluid treatment system of any preceding clause, wherein one or both of the first fluid substance and the second fluid substance is a medical fluid substance.

[0321] Item 56: A fluid processing system as described in any of the preceding items, wherein the fluid substance mixture is a colloidal suspension containing particles, and the particles, such as nanoparticles, are formed from one or more components of the first fluid substance and one or more components of the second fluid substance, optionally, the nanoparticles are nanoparticle compositions, such as polymer nanoparticles or particles containing lipids and polymers, such as lipid or liposome nanoparticles (LNP), lipid complexes (LPX), polyplexes (PPX).

[0322] Item 57: A fluid handling system as described in any of the preceding items, wherein the first fluid path is fluidly connected or fluidically connectable to a first reservoir comprising a first fluid substance, so that the first fluid substance can be driven from the first reservoir through the first fluid path to the mixing zone, and / or the second fluid path is fluidly connected or fluidically connectable to a second reservoir comprising a second fluid substance, so that the second fluid substance can be driven from the second reservoir through the second fluid path to the mixing zone.

[0323] Clause 58: The fluid treatment system of any preceding clause, wherein the fluid path system is a closed and / or uninterrupted system.

[0324] Clause 59: A fluid handling system as described in any of the preceding clauses, wherein the fluid handling system includes a storage area for collecting the fluid substance mixture, and the storage area is arranged downstream of the non-guided flow area along the flow direction of the fluid substance mixture in the fluid handling system.

[0325] Item 60: A fluid processing system as described in Item 59, wherein the fluid substance mixture forms a surface in the storage area, for example, on the side facing the non-guided flow area as seen in the direction opposite to the flow direction of the fluid substance mixture to the storage area, which defines the storage area.

[0326] Item 61: A fluid handling system as described in Item 60, wherein the fluid handling system is configured so that the fluid substance mixture enters the reservoir area via the surface after flowing through the non-guided flow area, for example, impinging on the surface in the form of a fluid jet or fluid droplets.

[0327] Clause 62: A fluid handling system as described in any of clauses 59 to 61, wherein the fluid handling system includes a reservoir area outlet, the reservoir area outlet is connected to the reservoir area fluid, and the reservoir area outlet is used to remove contents, such as a fluid substance mixture, from the reservoir area.

[0328] Clause 63: The fluid treatment system of any one of Clauses 59 to 62, wherein the fluid substance mixture in the reservoir region is in transverse contact with an interior wall defining the fluid treatment system.

[0329] Clause 64: The fluid treatment system of any of clauses 59 to 63, wherein the fluid path system comprises the reservoir region.

[0330] Clause 65: The fluid treatment system of any of Clauses 59 to 64, wherein the reservoir region is disposed within a container.

[0331] Clause 66: The fluid treatment system of any one of clauses 59 to 65, wherein the reservoir region or the container has a volume greater than the mixing region.

[0332] Clause 67: The fluid treatment system of any one of clauses 59 to 66, wherein the reservoir zone or the container has a smaller volume than the mixing zone.

[0333] Clause 68: A fluid handling system as described in any of clauses 66 to 67, wherein the container has a fill capacity greater than or equal to: 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.

[0334] Clause 69: A fluid processing system as described in any one of clauses 66 to 68, wherein the container has a fill capacity less than or equal to: 1000L, 900L, 800L, 700L, 600L, 500L, 400L, 300L, 200L, 150L, ​​100L, 50L, 45L, 40L, 35L, 30L, 25L, 20L, 15L, 10L, 5L.

[0335] Clause 70: A fluid handling system as described in any 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.

[0336] Clause 71: The fluid treatment system of any of clauses 65 to 70, wherein at least a portion of the non-directed flow zone or the entire non-directed flow zone is within the container.

[0337] Item 72: A fluid handling system as described in any of items 65 to 71, wherein the fluid handling system (e.g., container) includes a port for adding additional substances to the fluid substance mixture, for example downstream of the non-guided flow zone and / or in the container.

[0338] Item 73: A fluid handling system as described in any of the preceding items, wherein the fluid handling system is configured so that the fluid substance mixture is directed away from the non-guided flow area downstream of the non-guided flow area to an outlet of the fluid handling system or fluid path system, for example so that the fluid substance mixture can be continuously discharged from the fluid handling system via the outlet.

[0339] Clause 74: A fluid handling system as described in any of the preceding clauses, wherein the fluid path system includes an increased diameter of the mixture fluid path of the fluid path system in the non-guided flow area, so that non-guided flow of the fluid substance mixture in the non-guided flow area is possible.

[0340] Clause 75: The fluid treatment system of Clause 74, wherein a diameter of the mixture fluid path varies within the non-guided flow region.

[0341] Item 76: A fluid handling system as described in item 74 or 75, wherein the diameter of the mixture fluid path increases in the direction of the mixture fluid path away from the mixing zone in the non-guided flow zone, such as increasing and / or continuously increasing in at least part of the mixture fluid path.

[0342] Clause 77: A fluid handling system as described in any of clauses 74 to 76, wherein the diameter of the mixture fluid path decreases in the direction away from the mixing zone in the non-guided flow zone, such as decreasing and / or continuously decreasing in at least part of the mixture fluid path.

[0343] Clause 78: The fluid treatment system of any preceding clause, wherein the fluid treatment system comprises an agitator for agitating the fluid substance.

[0344] Clause 79: The fluid treatment system of Clause 78, wherein the agitator is arranged to agitate the fluid substance mixture, such as in the reservoir region.

[0345] Clause 80: The fluid treatment system of Clause 78 or 79, wherein the agitator is disposed within the contents to be agitated.

[0346] Clause 81: The fluid treatment system of any one of Clauses 78 to 80, wherein the stirrer is a magnetic stirrer, such as a magnetic stir bar.

[0347] Clause 82: The fluid treatment system of any preceding clause, wherein the mixing zone has a first inlet for the first fluid substance and a second inlet for the second fluid substance.

[0348] Clause 83: The fluid treatment system of any preceding clause, wherein the mixing zone is formed by a mixing element connected to a first conduit defining a first fluid path and / or a second conduit defining a second fluid path.

[0349] Clause 84: The fluid treatment system of Clause 74, wherein the mixing element has an outlet toward the non-guided flow zone, optionally, the outlet is toward or is part of the guided zone.

[0350] Clause 85: The fluid treatment system of clause 84 or 83, wherein the mixing element is a T-shaped element, a Y-shaped element, an X-shaped element, or an element having a psi geometry.

[0351] Clause 86: The fluid treatment system of any preceding clause, wherein the mixing zone is provided by a portion of a continuous conduit structure having further portions providing the first and second fluid paths. The first and second fluid paths are fluidly separated from each other until the mixing zone.

[0352] Item 87: A fluid handling system as described in any of the preceding items, wherein the piping structure for the first fluid path, the second fluid path and / or the mixing zone can be made of or include plastic, such as medical grade plastic and / or polypropylene or polyvinylidene fluoride (PVDF), or made of or include non-plastic material, such as medical grade material such as stainless steel.

[0353] Clause 88: The fluid treatment system of any preceding clause, wherein the fluid treatment system is configured to provide turbulent mixing of the first fluid substance and the second fluid substance in the mixing zone.

[0354] Clause 89: A method for treating a fluid, comprising: directing the first fluid substance and the second fluid substance within the fluid path system to a mixing zone to form a fluid substance mixture, and The fluid substance mixture in the non-guided flow zone is prevented from contacting a wall of the fluid path system along the flow direction of the fluid substance mixture downstream of the mixing zone for a predetermined period of time.

[0355] Clause 90: A method of treating a fluid according to clause 89, wherein the predetermined time period is less than or equal to one of the following: 1s, 950ms, 900ms, 850ms, 800ms, 750ms, 700ms, 650ms, 600ms, 550ms, 500ms, 450ms, 400ms.

[0356] Clause 91: A method of treating a fluid according to clause 89 or 90, wherein the predetermined time period is greater than or equal to one of: 1 ms, 5 ms, 10 ms, 20 ms, 25 ms, 50 ms, 100 ms, 150 ms, 200 ms, 300 ms.

[0357] Item 92: A method for treating a fluid according to any one of items 89 to 91, wherein the first fluid substance and the second fluid substance are selected so that the fluid substance mixture produced by mixing the first fluid substance and the second fluid substance has an intermediate state, for example during and / or immediately after mixing the first fluid substance and the second fluid substance.

[0358] Clause 93: The method of treating a fluid according to clause 92, wherein the intermediate state is a transient state, such as a state that exists only for less than a predetermined period of time.

[0359] Item 94: A method for treating a fluid according to any one of items 89 to 93, wherein the first substance mixture and the second substance mixture are directed through the mixing zone for a time period of at least greater than or equal to 10 ms and less than or equal to 80 ms, for example greater than or equal to 20 ms and less than or equal to 60 ms, to form a fluid substance mixture.

[0360] Clause 95: A method of treating a fluid according to any one of clauses 89 to 94, wherein

[0361] Directing the first fluid to the mixing zone includes directing the fluid substance mixture through the first fluid zone of the fluid path system, and / or

[0362] Directing the second fluid to a mixing zone includes directing the fluid substance mixture through a second fluid zone of the fluid path system.

[0363] Clause 96: The method of treating a fluid according to any one of clauses 89 to 95, further comprising: The fluid substance mixture is directed through a guide zone downstream from the mixing zone to direct the fluid substance mixture toward the non-guided flow zone.

[0364] Clause 97: The method of treating a fluid according to any one of clauses 89 to 95, further comprising: guiding the fluid substance mixture within a fluid guiding element of a fluid path system located downstream of the non-guided flow zone, and / or The fluid substance mixture is received in a fluid retaining element of a fluid path system downstream from the non-guided flow zone.

[0365] Clause 98: The method of treating a fluid according to any one of clauses 89 to 97, further comprising: directing the first fluid and the second fluid simultaneously to the mixing zone.

[0366] Clause 99: The method of treating a fluid according to any one of clauses 89 to 98, further comprising: Fluid flow of the first fluid is driven with a first flow actuator, such as a pump, eg, a syringe pump, a peristaltic pump, a pressurized container, a diaphragm pump, and / or a piston pump.

[0367] Clause 100: The method of treating a fluid according to any one of clauses 89 to 99, further comprising: Fluid flow of the second fluid is driven with a second flow actuator, such as a pump, eg, a syringe pump, a peristaltic pump, a pressurized container, a diaphragm pump, and / or a piston pump.

[0368] Clause 101: The method of treating a fluid according to any one of clauses 89 to 100, further comprising: Downstream of the non-guided flow zone, the flow of the fluid substance mixture is driven by a mixture flow driver, such as a pump, such as a syringe pump, peristaltic pump, diaphragm pump and / or piston pump, or a pressurized container.

[0369] Clause 102: The method of treating a fluid according to any one of clauses 89 to 101, further comprising: The fluid material mixture is moved through a free fall or free flow zone, which is the non-guided flow zone.

[0370] Clause 103: A method of treating a fluid according to any one of clauses 89 to 102, wherein the fluid treatment system is configured to operate at a flow rate and / or have a diameter of the flow path such that for a fluid having a flow rate of 1 g / cm3 for water with a density of 1 cP, a viscosity of 1 cP and a temperature of 20°C, the relationship between the flow rate and the diameter of the flow path results in the flow at the mixing zone, the guide zone, the first inlet, the second inlet and / or the outlet (e.g., the outlet of the mixing zone) being characterized in that the calculated Reynolds number (Re) is greater than or equal to one of the following values: 10000, 7500, 5000, 4000, 3000, 2900, 2800, 2700, 2600, 2500.

[0371] Clause 104: A method of treating a fluid according to any one of clauses 89 to 103, wherein the fluid treatment system is configured to operate at a flow rate and / or have a diameter of the flow path such that for a fluid having a flow rate of 1 g / cm 3 of water with a density of 1 cP, a viscosity of 1 cP and a temperature of 20°C, the relationship between the flow rate and the diameter of the flow path results in the flow at the mixing zone, the guide zone, the first inlet, the second inlet and / or the outlet (e.g., the outlet of the mixing zone) being characterized in that the calculated Reynolds number (Re) is greater than or equal to one of the following values: 500, 1000, 1100, 1200, 1300, 1400, 1500, 1700, 1800, 1900, 2000.

[0372] Clause 105: The method of treating a fluid according to any one of clauses 89 to 104, wherein the method is performed using the fluid treatment system of any one of clauses 1 to 88.

[0373] Clause 106: Use of the fluid treatment system of any of clauses 1 to 88 for mixing a first fluid substance with a second fluid substance to provide a fluid substance mixture.

[0374] Item 107: A fluid substance mixture obtainable or obtained according to the method for treating a fluid according to any one of items 89 to 106.

[0375] Reference numerals

[0376] 20 Pipeline Existing Technology

[0377] 100 Fluid Handling Systems

[0378] 202 first fluid path

[0379] 204 Second fluid path

[0380] 206 First Mobile Driver

[0381] 208 Second Mobile Driver

[0382] 300 Mixed Zone

[0383] 302 Mixed Zone (First) Entrance

[0384] 304 Mixed Zone (Second) Entrance

[0385] 304a, 304b Second entrance

[0386] 306 Mixed Components

[0387] 400 Non-guided flow area

[0388] 402 Non-guided flow area wall

[0389] 404 Non-guided flow area wall

[0390] 406 fluid guiding element

[0391] 408a, 408b Widened fluid path

[0392] 410 Entrance Area

[0393] 500 Guide Area

[0394] 600 Free Fall Zone

[0395] 602 First Storage

[0396] 604 Second Storage

[0397] 700 Storage Area

[0398] 702 Surface

[0399] 704 Fluid Matter Mixture Droplets

[0400] 706 Exit

[0401] 708 Mixture Flow Driver

[0402] DP1 Sediment

[0403] DP2 sediment

[0404] AR1 Flow direction of fluid material mixture

[0405] AR2 Fluid Flow of the First Fluid Material

[0406] AR3 Fluid Flow of Second Fluid Material

[0407] AR4 enters flow direction

[0408] AR6 into the flow direction

[0409] AR7 Non-guided flow area spindle

[0410] F1 First fluid substance

[0411] F2 Second fluid substance

[0412] MX fluid substance mixture

[0413] S1 method first step

[0414] S2 method first step

Claims

1. A fluid handling system comprising: - A fluid path system, the fluid path system comprising: - a first fluid path directing a first fluid substance towards a mixing zone of said fluid path system, - a second fluid path directing a second fluid substance towards said mixing zone, wherein the mixing zone is arranged in fluid communication with the first fluid path and the second fluid path, such that the first fluid substance and the second fluid substance can mix in the mixing zone to form a fluid substance mixture, The fluid handling system includes a non-guided flow zone, wherein the non-guided flow zone is configured so that when the fluid substance mixture flows through the non-guided flow zone, the fluid substance mixture can contact or be prevented from contacting an inner wall suitable for guiding the fluid substance mixture to flow along the flow direction of the fluid substance mixture, and wherein the non-guided flow zone extends a predetermined distance downstream of the mixing zone, for example, only extends the predetermined distance.

2. The fluid treatment system of claim 1, wherein a fluid guiding element or a fluid retaining element of the fluid treatment system is located downstream of the non-guided flow zone to receive and / or guide the fluid substance mixture.

3. The fluid treatment system of any one of the preceding claims, wherein the fluid treatment system is configured such that the first and second fluid substances can be moved to the mixing zone simultaneously.

4. A fluid handling system as described in any one of the preceding claims, wherein the fluid path system includes a guide zone arranged between the mixing zone and the non-guide flow zone along the flow direction of the fluid substance mixture, wherein the guide zone is configured to determine the entry flow direction of the fluid substance mixture, and the fluid substance mixture enters the non-guide flow zone along the entry flow direction.

5. A fluid handling system as claimed in any one of the preceding claims, wherein for the predetermined distance, the fluid handling system has a free fall zone or a free flow zone, for example due to an interruption of the fluid path system in the non-guided flow area and / or due to the mixture fluid path of the fluid path system being configured to have an appropriate width in the non-guided flow area, and the free fall zone or the free flow zone allows the fluid substance mixture to flow through the fluid handling system without contacting an inner wall of the fluid handling system, for example an inner wall closest to the fluid substance mixture.

6. A fluid treatment system as claimed in any preceding claim, wherein the predetermined distance is selected such that the fluid substance mixture may contact or is prevented from contacting the inner wall for a predetermined period of time, such as during operation of the fluid treatment system.

7. A fluid treatment system as described in claim 6, wherein the predetermined time period is less than or equal to one of the following: 1s, 950ms, 900ms, 850ms, 800ms, 750ms, 700ms, 650ms, 600ms, 550ms, 500ms, 450ms, 400ms, and / or the predetermined time period is greater than or equal to one of the following: 1ms, 5ms, 10ms, 20ms, 25ms, 50ms, 100ms, 150ms, 200ms, 300ms.

8. A fluid handling system as described in any of the preceding claims, wherein the first fluid substance and the second fluid substance are selected so that the fluid substance mixture produced by mixing the first fluid substance and the second fluid substance has an intermediate state, for example during and / or immediately after mixing the first fluid substance and the second fluid substance.

9. The fluid treatment system defined in claim 8, wherein the intermediate state is a transient state, such as a state that exists only for less than a predetermined period of time.

10. The fluid treatment system of any one of claims 8 to 9, wherein the fluid substance mixture is more prone to forming deposits on walls, such as interior walls defining a fluid path, in its intermediate state than in its stable state.

11. The fluid treatment system of any one of claims 8 to 10, wherein the fluid treatment system is configured such that the fluid substance mixture flows in the non-guided flow zone in its intermediate state.

12. A fluid handling system as described in any one of claims 8 to 11, wherein the fluid handling system is configured and / or operable so that the fluid substance mixture flows only in the mixing zone and / or the non-guided flow zone and / or optionally the guided zone in its intermediate state.

13. A fluid handling system as described in any of the preceding claims, wherein the first fluid substance and the second fluid substance are selected to form a fluid substance mixture containing colloids, for example, the colloids have an average particle size greater than or equal to 10 nm and / or less than or equal to 1000 nm.

14. The fluid treatment system of any preceding claim, wherein the first fluid substance comprises a nucleic acid, a peptide, or a protein.

15. The fluid treatment system of any preceding claim, wherein the second fluid substance comprises a colloidal suspension, such as an ionic colloidal suspension, such as a cationic colloidal suspension.

16. A fluid handling system as described in any one of the preceding claims, wherein the fluid handling system is configured so that the fluid substance mixture is guided away from the non-guided flow area downstream of the non-guided flow area to the outlet of the fluid handling system or the fluid path system, for example so that the fluid substance mixture can be continuously discharged from the fluid handling system via the outlet.

17. A fluid handling system as described in any of the preceding claims, wherein the fluid handling system includes an increased diameter of the mixture fluid path of the fluid path system in the non-guided flow area, so that non-guided flow of the fluid substance mixture in the non-guided flow area is possible.

18. The fluid treatment system defined in Claim 17, wherein a diameter of the mixture fluid path varies in the non-directed flow zone.

19. The fluid treatment system of claim 17 or 18, wherein the diameter of the mixture fluid path increases in the direction away from the mixing zone in the non-guided flow zone, such as increasing and / or continuously over at least a portion of the mixture fluid path; or The diameter of the mixture flow path decreases in the direction away from the mixing zone in the non-guided flow zone, for example, decreases and / or continuously decreases in at least a portion of the mixture flow path.

20. The fluid treatment system of any preceding claim, wherein the mixing zone is formed by a mixing element connected to a first conduit defining the first fluid path and / or a second conduit defining the second fluid path.

21. The fluid treatment system of any preceding claim, wherein the fluid treatment system is configured to provide turbulent mixing of the first fluid substance and the second fluid substance in the mixing zone.

22. A method for treating a fluid, comprising: directing the first fluid substance and the second fluid substance within the fluid path system to a mixing zone to form a fluid substance mixture, and The fluid substance mixture in the non-guided flow zone is prevented from contacting a wall of the fluid path system along the flow direction of the fluid substance mixture downstream of the mixing zone for a predetermined period of time.

23. A method for treating a fluid as described in claim 22, wherein the predetermined time period is less than or equal to one of the following: 1s, 950ms, 900ms, 850ms, 800ms, 750ms, 700ms, 650ms, 600ms, 550ms, 500ms, 450ms, 400ms, and / or wherein the predetermined time period is greater than or equal to one of the following: 1ms, 5ms, 10ms, 20ms, 25ms, 50ms, 100ms, 150ms, 200ms, 300ms.

24. A method for treating a fluid as described in any one of claims 22 to 23, wherein the first fluid substance and the second fluid substance are selected so that the fluid substance mixture produced by mixing the first fluid substance and the second fluid substance has an intermediate state, for example during and / or immediately after mixing the first fluid substance and the second fluid substance.

25. A method for treating a fluid as claimed in claim 24, wherein the intermediate state is a transient state, such as a state that exists only for less than a predetermined period of time.

26. A method for treating a fluid as described in any one of claims 22 to 25, wherein the first substance mixture and the second substance mixture are directed through the mixing zone for a time period of at least greater than or equal to 10 ms and less than or equal to 80 ms, for example greater than or equal to 20 ms and less than or equal to 60 ms, to form a fluid substance mixture.

27. The method for treating a fluid according to any one of claims 22 to 26, further comprising: The fluid substance mixture is directed through a guide zone downstream from the mixing zone to direct the fluid substance mixture toward the non-guided flow zone.

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

29. The method for treating a fluid according to any one of claims 22 to 28, further comprising: The fluid material mixture is moved through a free fall or free flow zone, which is the non-guided flow zone.

30. A method for treating a fluid as claimed in any one of claims 22 to 29, wherein the method is carried out using the fluid treatment system as claimed in any one of claims 1 to 21.

31. Use of the fluid treatment system of any one of claims 1 to 21 for mixing a first fluid substance with a second fluid substance to provide a fluid substance mixture.

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

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