Microfluidic device

Abstract

A separation assembly has a microfluidic separation element having a substrate layer. The microfluidic separation element defines an element inlet, a first element outlet, and a second element outlet. A first element outlet is defined by the base layer. The permeate discharge layer adjoins the substrate layer. The permeate discharge layer is downstream of the first element outlet.

Description

priority

[0001] This application claims the benefit of U.S. Provisional Application No. 63 / 455,886, filed March 30, 2023, the disclosure of which is incorporated herein by reference in its entirety. Technical Field

[0002] This disclosure relates generally to microfluidic devices. More specifically, this disclosure relates to microfluidic devices as particle separators. Summary of the Invention

[0003] Some embodiments of the technology disclosed herein relate to a separation assembly having a microfluidic separation element having a substrate layer. The microfluidic separation element defines an element inlet, a plurality of first element outlets, and a second element outlet. The plurality of first element outlets are defined by the substrate layer. A permeate discharge layer is adjacent to the substrate layer. The permeate discharge layer is downstream of the plurality of first element outlets.

[0004] In some such embodiments, the permeate discharge layer extends laterally across the base layer. Additionally or alternatively, the separation assembly is a component of a cell retention device in a perfusion bioreactor. Additionally or alternatively, the microfluidic separation element is a hydrodynamic separator element. Additionally or alternatively, the permeate discharge layer is defined by a mesh material. Additionally or alternatively, the permeate discharge layer is a layer of material defining microchannels downstream of the plurality of first element outlets. Additionally or alternatively, the separation assembly further has a first microfluidic channel defining: a channel inlet downstream of the element inlet; and a channel outlet having a first channel outlet upstream of a first element outlet among the plurality of first element outlets, and a second channel outlet upstream of a second element outlet. Additionally or alternatively, the first microfluidic channel is tortuous.

[0005] Additionally or alternatively, the separation assembly has a plurality of microfluidic channels having the first microfluidic channel. Each microfluidic channel defines: a channel inlet downstream of the element inlet, a first channel outlet upstream of the first element outlet among the plurality of first element outlets, and a second channel outlet upstream of the second element outlet. Additionally or alternatively, each of the plurality of microfluidic channels is nested with an adjacent microfluidic channel. Additionally or alternatively, the plurality of microfluidic channels has at least six microfluidic channels. Additionally or alternatively, each microfluidic channel is within 12 mm, 10 mm, 5 mm, or 3 mm of an adjacent microfluidic channel. Additionally or alternatively, each microfluidic channel is tortuous. Additionally or alternatively, each microfluidic channel defines two curves in opposite directions. Additionally or alternatively, each microfluidic channel has an inner wall and an outer wall, and each microfluidic channel is configured to enrich particles in the liquid stream toward the inner wall. Additionally or alternatively, the length of each of the plurality of microfluidic channels defines an arc of less than or equal to 270°.

[0006] Some embodiments of this technology relate to a system having multiple separation components consistent with the aforementioned separation components, wherein these separation components are arranged in a stacked configuration. The system inlet is in direct fluid communication with the inlet of each component. These separation components are arranged to operate in parallel.

[0007] Additionally or alternatively, the length of each of the plurality of microfluidic channels defines an arc of less than or equal to 200°. Additionally or alternatively, the microfluidic separation element is configured to separate particles ranging from 10 to 20 micrometers from the liquid stream. Additionally or alternatively, the microfluidic separation element is configured to separate one or both of fish cells and avian cells from the liquid stream. Additionally or alternatively, the microfluidic separation element is configured to separate one or both of mammalian cells and insect cells from the liquid stream.

[0008] Some embodiments of the technology disclosed herein relate to a hydrodynamic separator element having a base layer defining a layer inlet, a plurality of first layer outlets, a second layer outlet, an outlet flow path upstream of the second layer outlet, and a plurality of tortuous microfluidic channels arranged in parallel. Each microfluidic channel defines a channel inlet downstream of the layer inlet, a first channel outlet upstream of one of the plurality of first layer outlets, and a second channel outlet upstream of the outlet flow path. The base layer is impermeable. Each of the plurality of microfluidic channels is nested with an adjacent microfluidic channel.

[0009] In some such embodiments, the length of each of the plurality of curved microfluidic channels defines an arc of less than or equal to 270°. Additionally or alternatively, the length of each of the plurality of curved microfluidic channels defines an arc of less than or equal to 200°. Additionally or alternatively, each microfluidic channel defines two curves in opposite directions. Additionally or alternatively, the plurality of curved microfluidic channels is at least six microfluidic channels. Additionally or alternatively, each microfluidic channel is within 10 mm, 5 mm, or 3 mm of adjacent microfluidic channels. Additionally or alternatively, the hydrodynamic separator element further has a permeate discharge layer adjacent to the substrate layer. The permeate discharge layer is downstream of the first layer outlet.

[0010] Additionally or alternatively, the permeate discharge layer extends laterally across the basement layer. Additionally or alternatively, the permeate discharge layer is defined by a mesh material. Additionally or alternatively, the permeate discharge layer is a layer of material defining microchannels downstream of the plurality of first-layer outlets. Additionally or alternatively, the hydrodynamic separator element is a component of the cell retention device of the perfusion bioreactor. Additionally or alternatively, each microfluidic channel has an inner wall and an outer wall, and each microfluidic channel is configured to enrich particles in the liquid stream toward the inner wall. Additionally or alternatively, the hydrodynamic separator element is configured to separate particles ranging from 10 to 20 micrometers from the liquid stream. Additionally or alternatively, the hydrodynamic separator element is configured to separate one or both of fish cells and avian cells in the liquid stream. Additionally or alternatively, the hydrodynamic separator element is configured to separate one or both of mammalian cells and insect cells in the liquid stream.

[0011] Additionally or alternatively, the hydrodynamic separator element has multiple substrate layers in a stacked configuration. The system inlet is in direct fluid communication with the inlet of each layer, and the multiple substrate layers are arranged to operate in parallel. Additionally or alternatively, a permeate discharge layer is adjacent to each substrate layer, wherein each permeate discharge layer is downstream of the outlet of its corresponding first layer.

[0012] Some embodiments of the technology disclosed herein relate to a system having a hydrodynamic separator element having an element inlet, a plurality of first element outlets, a second element outlet, and a plurality of tortuous microfluidic channels between the element inlet and the first element outlets. Each tortuous microfluidic channel has an inner wall and an outer wall, and the hydrodynamic separator element is configured to enrich particles along the inner wall. A tangential flow filter has a feed inlet, a permeate outlet, a permeate outlet, and a filter medium disposed between the feed inlet and the permeate outlet, downstream of the plurality of first element outlets.

[0013] In some such embodiments, the system further includes a cell culture vessel positioned downstream of the tangential flow filter. Additionally or alternatively, the hydrodynamic separator element has a base layer defining a layer inlet, a plurality of first layer outlets, and a second layer outlet. The layer inlet is downstream of the element inlet, each first layer outlet is upstream of a first element outlet among the plurality of first element outlets, and the second layer outlet is upstream of a second element outlet. Each of the plurality of tortuous microfluidic channels extends between the layer inlet and a first layer outlet among the plurality of first layer outlets. Additionally or alternatively, the system further includes a permeate discharge layer adjacent to the base layer. The permeate discharge layer is downstream of the first layer outlets.

[0014] Additionally or alternatively, the permeate discharge layer extends laterally across the base layer. Additionally or alternatively, the hydrodynamic separator element has multiple base layers in a stacked configuration. Each base layer defines a layer inlet, multiple first layer outlets, and a second layer outlet, as well as a tortuous microfluidic channel extending between the layer inlet and one of the multiple first layer outlets. Each layer inlet is downstream of the element inlet, each first layer outlet is upstream of one of the multiple first element outlets, and each second layer outlet is upstream of a second element outlet. Additionally or alternatively, the system further has a permeate discharge layer adjacent to each base layer. The permeate discharge layer is downstream of the corresponding first layer outlet. Additionally or alternatively, each permeate discharge layer extends laterally across the corresponding base layer. Additionally or alternatively, the permeate discharge layer is a material layer defining the microchannel downstream of the multiple first layer outlets. Additionally or alternatively, the permeate discharge layer is defined by a mesh material. Additionally or alternatively, each substrate layer defines a plurality of tortuous microfluidic channels, each tortuous microfluidic channel extending between the inlet of the layer and a first-layer outlet of the plurality of first-layer outlets.

[0015] Alternatively or additionally, each of the plurality of microfluidic channels is nested with an adjacent microfluidic channel. Alternatively or additionally, each substrate layer has at least six microfluidic channels. Alternatively or additionally, within each substrate layer, each microfluidic channel is within 12 mm, 10 mm, 5 mm, or 3 mm of an adjacent microfluidic channel. Alternatively or additionally, each microfluidic channel defines two curves in opposite directions. Alternatively or additionally, the length of each of the plurality of curved microfluidic channels defines an arc less than or equal to 270°.

[0016] Additionally or alternatively, the length of each of the plurality of curved microfluidic channels defines an arc of less than or equal to 200°. Additionally or alternatively, the hydrodynamic separator element is configured to separate particles with diameters ranging from 10 to 20 micrometers from the liquid stream. Additionally or alternatively, the hydrodynamic separator element is configured to separate one or both of fish cells and avian cells from the liquid stream. Additionally or alternatively, the hydrodynamic separator element is configured to separate one or both of mammalian cells and insect cells from the liquid stream.

[0017] The foregoing summary is not intended to describe every embodiment or every implementation. Rather, a more complete understanding of the illustrative embodiments will become clear and understood by referring to the following detailed description of exemplary aspects and claims in conjunction with the accompanying drawings. Attached Figure Description

[0018] The present technology can be more fully understood and appreciated in light of the following detailed description of various embodiments in conjunction with the accompanying drawings.

[0019] Figure 1 This is a schematic representation of an example microfluidic device consistent with the technology disclosed herein.

[0020] Figure 2 It is possible Figure 1 A three-dimensional view of a portion of an example microfluidic separator element used in the device.

[0021] Figure 3 yes Figure 2 Detailed view.

[0022] Figure 4 This is a cross-sectional view of an example flow channel consistent with the technology disclosed herein.

[0023] Figure 5 It is a side-facing view of multiple flow channels consistent with the technology disclosed herein.

[0024] Figure 6 yes Figure 2 A three-dimensional cross-sectional view of this part of an example microfluidic separator element.

[0025] Figure 7 This is another example of multiple flow channels consistent with the technology disclosed herein, presented in a side-facing view.

[0026] Figure 8 This is yet another example of multiple flow channels consistent with the technology disclosed herein, presented in a side-facing view.

[0027] Figure 9 This is yet another example of multiple flow channels consistent with the technology disclosed herein, presented in a side-facing view.

[0028] Figure 10 This is a cross-sectional schematic diagram of an example separator system consistent with the technology disclosed herein.

[0029] Figure 11 This is a schematic diagram of an example implementation consistent with the technology disclosed herein.

[0030] The accompanying drawings are presented primarily for clarity and are therefore not necessarily drawn to scale. Furthermore, various structures / components, including but not limited to fasteners, electrical components (wiring, cables, etc.), etc., may be shown schematically or removed from some or all views to better illustrate aspects of the depicted embodiments, or where including such structures / components is not necessary for understanding the various exemplary embodiments described herein. However, the absence of such structures / components shown / described in a particular figure should not be construed as limiting the scope of the various embodiments in any way. Detailed Implementation Exemplary microfluidic device

[0031] Some embodiments of the technology disclosed herein relate to a separation component 100, which is schematically represented in... Figure 1 As depicted in the figure. The separation assembly 100 typically has a microfluidic separator element 110 and a permeate discharge layer 130 adjacent to the microfluidic separator element 110.

[0032] Microfluidic separator element 110 is typically configured to receive a liquid flow containing dispersed particles and separate the liquid flow into two liquid streams. Microfluidic separator element 110 typically has a substrate layer 120, an element inlet 112, a plurality of first element outlets 114, and a second element outlet 118. Element inlet 112 is in direct fluid communication with the first element outlets 114 and the second element outlet 118. Element inlet 112 is typically configured to receive the fluid flow to be separated, i.e., the “feed” liquid stream. Each first element outlet 114 defines a fluid flow path for a first liquid stream (e.g., a “permeate” liquid stream) of the separated fluid exiting the separator element 110. The second element outlet 118 defines a fluid flow path for a second liquid stream (e.g., a “residue” liquid stream) of the separated fluid exiting the separator element.

[0033] As used herein, the term "particle" refers to a discrete amount of material dispersed in a fluid. Non-limiting examples of materials that can form particles include dirt, metals, cells, bubbles, fats, and water droplets. In one particular example, water droplets may be dispersed in a hydrocarbon fluid (such as gasoline or diesel fuel) to form an emulsion. In another example, bubbles may be dispersed in a hydraulic fluid. In yet another example, cells may be dispersed in an aqueous fluid. These cells may include eukaryotic cells. Example eukaryotic cells include mammalian cells, insect cells, plant cells, fungal cells, bacterial cells, etc. Other example eukaryotic cells include fish cells, crustacean cells, mollusc cells, and avian cells. In yet another example, particles may be pulp in orange juice, fat in milk, and impurities in beer or wine.

[0034] Microfluidic separator element 110 is configured to enrich suspended particles in a feed liquid stream, such that each element outlet 114, 116 can accommodate, for example, a liquid stream with a relatively high particle concentration (“particle-loaded” liquid stream) and a liquid stream with a relatively low particle concentration (“particle-deficient” liquid stream). Target particles can be within a specific size range or can have a minimum size. For example, microfluidic separator element 110 can be specifically designed for particles having a cross-sectional dimension (e.g., diameter) ranging from 5-30 μm, 6-25 μm, or 10-20 μm. For non-spherical particles, for the purposes of calculations provided herein, the particle diameter is considered to be the diameter of a volume equivalent sphere. In some other examples, microfluidic separator element 110 can be designed for particles having a cross-sectional dimension of at least 5 μm, at least 10 μm, at least 15 μm, or at least 20 μm. In some embodiments, a first element outlet 114 is configured to receive a particle-loaded liquid stream, and a second element outlet 118 is configured to receive a particle-deficient liquid stream. In some other embodiments, the second element outlet 118 is configured to receive a liquid jet loaded with particles, and the first element outlet 114 is configured to receive a liquid jet lacking particles.

[0035] The microfluidic separator element 110 is defined as any type of microfluidic device configured to separate a fluid containing suspended particles into a particle-loaded liquid stream and a particle-free liquid stream by means of liquid flowing through one or more flow channels defined by the microfluidic device. Each flow channel has a configuration that facilitates the separation of liquid containing dispersed particles flowing through it into a particle-loaded liquid stream and a particle-free liquid stream. In some embodiments, the microfluidic separator element 110 has multiple flow channels. In some other embodiments, the microfluidic separator element 110 has a single flow channel. In various embodiments, each flow channel has a height and width ranging from 20 to 1000 μm. In some embodiments, each flow channel is a microchannel. In some embodiments, the microfluidic separator element 110 is a hydrodynamic separator element, defined as a microfluidic device configured to aggregate particles within a liquid stream solely by forces caused by internal liquid flow.

[0036] Microfluidic separator element 110, consistent with the technology disclosed herein, typically has a substrate layer 120. Flow channels are defined in the substrate layer 120. The substrate layer 120 can be constructed from a variety of different materials and combinations thereof. In various embodiments, the substrate layer 120 is constructed from an impermeable material, meaning that the substrate layer 120 is not adapted for liquid flow through it except through openings / passages defined throughout the substrate layer 120, such as flow channels, inlets, and outlets. In some embodiments, the substrate layer 120 can be a polymer. In some examples, the substrate layer 120 is polydimethylsiloxane (PDMS). The substrate layer 120 can be composed of polymers such as acrylic acid, polypropylene, polycarbonate, polyethylene, cyclic olefin copolymers (COC), and combinations thereof. In some embodiments, the substrate layer 120 can include glass. In some embodiments, the substrate layer 120 can include a non-reactive metal. In some embodiments, the substrate layer 120 can include one or more adhesive layers, such as pressure-sensitive adhesives. In some embodiments, the substrate layer 120 is constructed from two or more materials.

[0037] It should be noted that in some embodiments, portions of the substrate 120 that define pathways for fluid flow (e.g., flow channels) may have a material coating to restrict particle adhesion to such pathways. Such coatings may include polyethylene glycol (PEG) chains or nonionic surfactants, such as those available from BASF under the trade name PLURONIC. Such coatings can be specifically configured to restrict cell adhesion through the fluid flow pathways.

[0038] In some embodiments, the microfluidic separator element 110 has an element inlet 112 defined toward a first lateral end 102 of the substrate 120, and a second element outlet 118 defined toward a second lateral end 104 of the substrate 120. In such embodiments, the microfluidic separator element 110 defines an outlet flow path 116 that extends laterally between the element inlet 112 and the second element outlet 118. In some embodiments, the microfluidic separator element 110 defines a single first element outlet 114, but in conjunction with... Figure 1 In other consistent embodiments, the microfluidic separator element 110 defines a plurality of first element outlets 114. Each first element outlet 114 may be laterally positioned between an element inlet 112 and a second element outlet 118. An outlet flow path 116 typically extends laterally between the element inlet 112 and each first element outlet 114. The flow channel configuration will be described in more detail below. In the current example, the second element outlet 118 facilitates liquid outflow from the assembly 100, and the first element outlet 114 facilitates liquid flow to the permeate discharge layer 130. In various embodiments, each first element outlet 114 is a defined opening extending axially through the substrate layer 120 to the permeate discharge layer 130. Permeate discharge layer

[0039] The permeate discharge layer 130 is configured to receive fluid from the first element outlet 114. Thus, the permeate discharge layer 130 is downstream of the first element outlet 114. The permeate discharge layer 130 is in direct fluid communication with the first element outlet 114. The permeate discharge layer 130 is generally adjacent to the base layer 120. The permeate discharge layer 130 generally extends laterally across the base layer 120. In some embodiments, the permeate discharge layer 130 extends co-linearly with the base layer 120.

[0040] A permeate discharge layer 130 defines a fluid volume 132 configured to receive liquid. In some embodiments, the fluid volume 132 is defined between a base layer 120 and a housing 134 of the permeate discharge layer 130. In some other embodiments, the housing 134 of the permeate discharge layer 130 encloses the fluid volume 132, and the housing 134 defines one or more openings facilitating direct fluid communication between each first element outlet 114 and the fluid volume 132. In some embodiments, the fluid volume 132 is a void volume, meaning an empty space. In some such embodiments, the housing 134 is a liquid-impermeable layer of material, and the fluid volume 132 is a fluid flow channel defined by the material layer between the housing 134 and the base layer 120. This fluid flow channel extends laterally across the material layer and extends across each first element outlet 114. This fluid flow channel is downstream of the plurality of first element outlets 114. In various embodiments, the fluid flow channel forming the fluid volume 132 is a microchannel. In various embodiments, the length of the fluid flow channel may be greater than or equal to the length spanning each first element outlet 114.

[0041] In some other embodiments, the fluid volume 132 is a porous material configured to receive liquid. In some embodiments, one or more spacers may be disposed in the fluid volume between the base layer 120 and the housing 134 to maintain the size and shape of the fluid volume 132. In some embodiments, the fluid volume 132 is defined by a mesh material disposed in the housing 134 of the permeate discharge layer 130, wherein the mesh material defines a volume configured to receive liquid.

[0042] The permeate discharge layer 130 typically has a permeate layer outlet 136 configured to facilitate liquid outflow from the assembly 100. In some embodiments, the permeate discharge layer 130 has a plurality of permeate layer outlets 136, each configured to facilitate liquid outflow from the fluid volume 132 of the assembly 100.

[0043] In some example implementations, with Figure 1 Two or more separator assemblies consistent with the corresponding description can be arranged in parallel, such that the element inlet 112 of another separator assembly substantially consistent with the separator assembly 100 described above is in fluid communication with the element inlets 112 of other separator assemblies within this group. In some such example embodiments, these separator assemblies can be arranged as a stack, wherein the permeate discharge layer 130 is adjacent to the subsequent microfluidic separator element 110. The element inlet 112 of the subsequent microfluidic separator element 110 receives the liquid flow in parallel with the element inlets of one or more other separator elements within the stack. In this configuration, the particle concentration (whether particle-loaded or particle-free) can be refined independently by each separator assembly 100.

[0044] In some alternative embodiments, one or more separator elements may be arranged in series, such that the particle concentration (whether particle-loaded or particle-deficient) from one of the first element outlet 114 or the second element outlet 118 can be iteratively refined by each subsequent separator assembly 100. In some such example embodiments, these separator assemblies may be arranged in a stack, with a permeate discharge layer 130 adjacent to a subsequent microfluidic separator element 110, wherein the element inlet 112 of the subsequent microfluidic separator element 110 receives a liquid flow from either the permeate layer outlet 136 or the second element outlet 118. In this configuration, the particle concentration (whether particle-loaded or particle-deficient) from the relevant outlet 136 / 118 can be iteratively refined by each subsequent separator assembly 100. In some such examples, the permeate layer outlet 136 is in fluid communication with the element inlet 112 of another separator assembly. In some such alternative examples, the second element outlet 118 may be in fluid communication with the element inlet 112 of another separator assembly, which is generally consistent with the aforementioned separator assembly 100.

[0045] It should be noted that, although Figure 1 The second element outlet 118 depicted extends in an axial direction away from the permeate discharge layer 130, but the second element outlet 118 may extend in any direction, and in at least one example, the second element outlet 118 extends in an axial direction past the permeate discharge layer 130 while bypassing it. Exemplary microfluidic separator element

[0046] Figure 2 Is with Figure 1 A perspective view of a portion of an exemplary substrate layer 120 of a consistent example microfluidic separator element 110, and Figure 3 yes Figure 2 A detailed view. More specifically, Figure 2 This is a perspective view of a substrate 120, which typically defines multiple flow channels for a microfluidic separator element 110. In various examples, the microfluidic separator element 110 has a cover layer 122 sealed to the substrate 120. Figure 1 This cover seals the axial ends of the flow channels(s) defined by the base layer 120. (See also: Special Reference) Figure 2 , Figure 1 The cover layer 122 will be configured to seal the top side (relative to) the flow channels (multiple) Figure 2 For the visibility of (multiple) flow channels, from Figure 2 The overlay layer 122 is omitted.

[0047] Microfluidic separator element 110 has a first microfluidic channel 140 and a channel outlet, the first microfluidic channel defining an inlet 112 of the element. Figure 1 Downstream channel entrance 142 ( Figure 3 ), and a channel outlet including a first channel outlet 141 and a second channel outlet 143. The first microfluidic channel 140 is typically configured to accommodate liquid flow. The first channel outlet 141 is located at the first element outlet 114 ( Figure 1 Upstream of ), and the second channel outlet 143 is at the second element outlet 118 ( Figure 1 Upstream of ), as described above, as the liquid flows from the channel inlet toward the channel outlets 141 and 143, particles suspended in the liquid within a certain size range can accumulate in one of the two channel outlets 141 and 143.

[0048] As an example, the microfluidic channel 140 can be formed in the substrate layer 120 by molding, photolithography, and 3D printing. In some examples, the microfluidic channel 140 is formed in the substrate layer 120 by injection molding or imprinting of plastic. Other methods can also be used to form the microfluidic channel 140.

[0049] The first microfluidic channel 140 defines a channel length L from the channel inlet 142 to the first channel outlet 141. D The first microfluidic channel 140 has a generally curved length and defines an arc. Typically, the length of the first microfluidic channel 140 defines an arc less than or equal to 270° and, in some embodiments, less than or equal to 200°. In various examples, such as with… Figure 3 In a consistent example, the length of the first microfluidic channel 140 is defined by an arc of approximately 180° about the central axis x. The length of the first microfluidic channel 140 can be curved while defining an inner radius R about the central axis x. C Thus, the length of the first microfluidic channel 140 can extend circumferentially around the central axis x. In the current example, the inner radius R... C The length along the first microfluidic channel 140 is substantially constant, but in some other examples, the inner radius R... C This can be varied. In the current example, the length of the first microfluidic channel 140 extends approximately 180° around the central axis x.

[0050] In the current example, the first microfluidic channel 140 defines a single curve, but in some other examples, the microfluidic channel 140 defines two or more connected curves. For example, the first microfluidic channel 140 may define two curves in opposite directions. An example of a first microfluidic channel 140 defining two curves in opposite directions would be an "S-shape," where a first portion of the first microfluidic channel 140 bends in a first direction, and a second portion of the first microfluidic channel 140 bends in a second, opposite direction. Examples of this configuration will be described in more detail below.

[0051] In the current example, the first microfluidic channel 140 generally has a rectangular cross-section along the length of the channel, which in Figure 4 As can be seen, the cross-section of the first microfluidic channel 140 is generally perpendicular to the direction in which the liquid flows through the first microfluidic channel 140. The first microfluidic channel 140 has a height (h) and a width (w), which is... Figure 4 As can be seen, the first microfluidic channel 140 has an inner wall 144 and an outer wall 146, wherein the inner wall 144 is a wall defining an inner radius of curvature Rc, and the outer wall 146 defines an outer radius. The width w of the first microfluidic channel 140 is the distance between the inner wall 144 and the outer wall 146. The first microfluidic channel 140 also has a hydraulic diameter (D). H The hydraulic diameter of a microfluidic channel with a rectangular cross-section is calculated using the following equation:

[0052] The first microfluidic channel 140 is configured to receive a liquid with a Reynolds number (Re) within the liquid channel. The liquid flow within the tortuous channel is described by two dimensionless numbers (i.e., the Reynolds number and the Dean number). The Reynolds number describes the ratio of inertial forces to viscous forces and is defined as: Where ρ is the fluid density, U is the average fluid velocity, and μ is the dynamic viscosity of the fluid. In hydrodynamic separators, the Reynolds number is typically small (<1000), meaning the flow profile is laminar. In various embodiments, the system is configured to have a Dean number (De) between 5 and 25. In various embodiments, the system is configured to have a Dean number between 5 and 20. The Dean number describes the fluid behavior in a tortuous pipe and illustrates the inertial forces, centripetal forces, and viscous forces acting on the fluid. The Dean number is defined as:

[0053] Microfluidic separator element 110 is typically configured to enrich particles in the first microfluidic channel 140. In various embodiments, separator element 110 is configured to enrich particles with a diameter greater than 8% of the hydraulic diameter of the first microfluidic channel 140. When the Dean number is in the range of 5 to 25, particles with a diameter greater than 8% of the channel's hydraulic diameter are typically enriched toward the inner wall. Hydrodynamic separators are typically configured to enrich particles with a diameter less than or equal to 50% of the channel height. In various embodiments, hydrodynamic separators consistent with the technology disclosed herein are configured to enrich particles with a density up to three times the density of the liquid in the first microfluidic channel 140. Example microfluidic channel

[0054] In various embodiments consistent with the technology disclosed herein, the microfluidic separator element 110 has a plurality of microfluidic channels 150 including a first microfluidic channel 140. Each of the plurality of microfluidic channels 150 is consistent with the description herein of the first microfluidic channel 140. Thus, each of the plurality of microfluidic channels 150 defines a channel inlet 152 downstream of the element inlet 112. Figure 1 The plurality of microfluidic channels 150 include a first channel outlet 151 upstream of the first element outlet 114 and a second channel outlet 153 upstream of the second element outlet 118. Similarly, in various embodiments, each of the plurality of microfluidic channels 150 has an inner wall and an outer wall, and each microfluidic channel is configured to enrich particles in the liquid stream toward the inner wall. The plurality of microfluidic channels 150 are typically arranged to operate in parallel with respect to the liquid flow through the microfluidic separator element 110.

[0055] The plurality of microfluidic channels 150 are positioned relatively close together to provide a relative increase in liquid flow capacity that the microfluidic separator element 110 can accommodate. In various embodiments, the substrate layer 120 defines at least four, at least six, or at least ten microfluidic channels.

[0056] In various embodiments, the plurality of microfluidic channels 150 are arranged in a pattern across the substrate 120 in a lateral direction. In some embodiments, the pattern is a regular pattern. In some embodiments, including Figure 2 In the depicted embodiment, each of the plurality of microfluidic channels 150 is nested with an adjacent microfluidic channel, meaning that each of the plurality of microfluidic channels 150 defines at least one arc along its length, the at least one arc defining a concave region between the channel inlet 152 and the channel outlets 151, 153, the concave region overlapping with the concave regions of the adjacent channels. An example of this is in Figure 5 As can be seen, this diagram is related to Figure 2 and Figure 3A lateral view of a portion of the plurality of microfluidic channels 150 in a consistent substrate layer 120. A first microfluidic channel 140 has a concave region 148 defined between an inlet 142 and a first channel outlet 141 (and a second channel outlet 143), which is received by a concave region 168 defined by a second microfluidic channel 160 between its channel inlet 162 and the first channel outlet 161, or by a concave region defined between its channel inlet 162 and the second channel outlet 163. Each of the plurality of microfluidic channels 150 is nested with an adjacent microfluidic channel.

[0057] In various embodiments, each microfluidic channel 150 is offset laterally from adjacent microfluidic channels 150 across the substrate layer 120. This offset can define a specific offset distance D1 between corresponding locations along adjacent microfluidic channels 150. For example, the channel inlet 142 of the first microfluidic channel 140 can be spaced apart from the channel inlet 162 of the second microfluidic channel 160 by an offset distance D1. The offset distance D1 is not particularly limited, but will generally be smaller than the radius of curvature of the curve defined by the microfluidic channel. In some embodiments, D1 can be 20 mm or less, 18 mm or less, 16 mm or less, 14 mm or less, or even 12 mm or less. In some embodiments, D1 is constant, meaning that the lateral offsets between adjacent microfluidic channels 150 are substantially equal.

[0058] Each of the plurality of microfluidic channels 150 can be positioned within a specific lateral distance D2 from the adjacent microfluidic channel. This means that a first position along the length of a specific microfluidic channel 150 is within a specific lateral distance D2 of a second position along the length of the adjacent microfluidic channel, wherein the second position does not necessarily correspond to the first position. Figure 5 As can be seen, as an example, the lateral distance D2 between the second channel outlet 163 and the first microfluidic channel 140 is less than the offset distance D1 between the first microfluidic channel 140 and the second microfluidic channel 160. In some embodiments, the lateral distance D2 of the microfluidic channels is within 12 mm or 10 mm of adjacent microfluidic channels. Each of the plurality of microfluidic channels 150 can be positioned within 5 mm of adjacent microfluidic channels. Each of the plurality of microfluidic channels 150 can be positioned within 3 mm of adjacent microfluidic channels. Each of the plurality of microfluidic channels 150 can be positioned within 2 mm of adjacent microfluidic channels.

[0059] Back to Figure 2 and Figure 3 The base layer 120 defines the layer inlet 124. Figure 2 ), multiple first-level exits 121 (in Figure 3(best visible in the middle) and second-level exit 123 ( Figure 2 Layer inlet 124 is typically configured to receive liquid flow from outside the substrate 120. Layer inlet 124 is upstream of each channel inlet 152. Inlet flow path 126 fluidly connects layer inlet 124 to each channel inlet 152, which includes channel inlet 142 of the first microfluidic channel 140. Each channel inlet 152 is sequentially arranged along the length of inlet flow path 126. Thus, fluid is configured to flow from element inlet 112 ( Figure 1 The fluid flows through inlet 124 along inlet flow path 126 to channel inlet 152. It should be noted that in some embodiments, the cross-sectional flow area defined by inlet flow path 126 gradually tapers from channel inlet 142 of the first microfluidic channel 140 to the channel inlet of the last microfluidic channel fluidly connected to inlet flow path 126. The taper of the cross-sectional flow area of ​​inlet flow path 126 can be configured to maintain a relatively constant average liquid flow velocity along the length of inlet flow path 126, although the liquid volume loss along the length of inlet flow path 126 to each of the microfluidic channels 150 is incremental. In some other embodiments, inlet flow path 126 has a cross-sectional flow area that remains constant along its length.

[0060] In Figure 1 In a consistent example, the layer inlet 124 of the base layer 120 receives a liquid flow from the element inlet 112, which is defined by the cover layer 122. In some other embodiments, the layer inlet is the element inlet, such as in embodiments where the liquid flow path extends laterally through the axial surface 125 of the base layer 120 to reach the inlet flow path 126.

[0061] Each first-layer outlet 121 defines a fluid flow path exiting the substrate layer 120. Each first-channel outlet 151 is upstream of the first-layer outlet 121. Each first-channel outlet 151 (including the first channel outlet 141 of the first microfluidic channel 140) is upstream of the first element outlet 114, which is located in... Figure 1 The illustration is shown in the diagram, and specific examples are shown in the diagram. Figure 6 It is shown in more detail in the middle. Figure 6 This is a cross-sectional view of the substrate 120 through each first channel outlet 151. In the current example, each first layer outlet 121 extends axially through the substrate 120 and fluidly connects the corresponding first channel outlet 151 to the outside of the substrate 120. The first layer outlet 121 may be the same fluid flow path as the first element outlet 114. In various embodiments, such as with Figure 1 The illustration in Figure 1In one embodiment, each first element outlet 114 fluidly connects the corresponding first channel outlet 151 to the permeate discharge layer 130.

[0062] The second-layer outlet 123 defines the fluid flow path leaving the base layer 120. The microfluidic separator element 110 has an outlet flow path 116. Figure 2 and Figure 3 The outlet flow path is in fluid communication with component inlet 112 and second component outlet 118, wherein, for example, component inlet 112 and second component outlet 118 are in... Figure 1 The diagram is schematically depicted. More specifically, the outlet flow path 116 extends between the element inlet 112 and the second element outlet 118. The outlet flow path 116 is downstream of the element inlet 112. The outlet flow path 116 is downstream of each second channel outlet 153. The outlet flow path 116 is upstream of the second element outlet 118. Thus, a portion of the liquid flowing through each of the plurality of microfluidic channels 150 (e.g., a liquid jet loaded with particles or lacking particles) flows through the corresponding second channel outlet 153 along the outlet flow path 116 through the second layer outlet 123 and exits from the microfluidic separator element 110 through the second element outlet 118.

[0063] Although Figure 2 , Figure 3 , Figure 5 and Figure 6 The examples depicted include multiple microfluidic channels 150 operating in parallel, but in some embodiments, the microfluidic separator element 110 has a single microfluidic channel. In some embodiments, the microfluidic separator element 110 has one or more microfluidic channels with alternative shapes, such as having a lateral profile different from the arcs depicted in the previously described figures.

[0064] Figure 7 It is a microfluidic separator element 110 (e.g.) Figure 1 (Example) A side-facing view of an example substrate 220 of a microfluidic separator element having a plurality of microfluidic channels 250 consistent with the technology disclosed herein. Each of the plurality of microfluidic channels 250 is generally consistent with the foregoing description of the microfluidic separator element and microfluidic channels, which is incorporated herein by reference, except as otherwise provided in the present description or Figure 7 The examples described in the text contradict each other.

[0065] The hydrodynamic separator element has a base layer 220 that defines a layer inlet 224, a plurality of first layer outlets 221, and a second layer outlet 223. The base layer 220 is generally impermeable. The base layer 220 defines an outlet flow path 216 upstream of the second layer outlet 223. The base layer 220 defines a plurality of tortuous microfluidic channels 250 arranged to operate in parallel. In various embodiments, the present technology includes at least six microfluidic channels 250 in the base layer 220. Each microfluidic channel 250 defines a channel inlet 252 downstream of the layer inlet 224. In the current example, an inlet flow path 226 fluidly connects the layer inlet 224 to the channel inlet 252, which may be consistent with the description of the inlet flow path elsewhere herein. Each microfluidic channel 250 defines a first channel outlet 251 upstream of the first layer outlets 221 of the plurality of first layer outlets. Each microfluidic channel 250 has a second channel outlet 253 upstream of the outlet flow path 216.

[0066] When a separator element with a base layer consistent with this example is combined with Figure 1 When using consistent components, it should be noted that each channel inlet 252 is configured to be in element inlet 112 ( Figure 1 Downstream of ), the first channel outlet 251 is configured to be at the first element outlet 114 ( Figure 1 Upstream of ), and the second channel outlet 253 is configured to be at the second element outlet 118 ( Figure 1 The upstream of the microfluidic channel 250. These multiple microfluidic channels 250 are typically arranged to operate in parallel with respect to the liquid flow through the microfluidic separator element. As previously described, each of the multiple microfluidic channels 250 has an inner wall and an outer wall (with...). Figure 4 (Consistent), and each microfluidic channel 250 can be configured to enrich particles in the liquid stream toward the inner wall. The particles can be in the range of 10-20 micrometers. In some examples, the particles are eukaryotic cells, such as mammalian or insect cells, or other cells as described above.

[0067] Similar to the example discussed above, each of the plurality of microfluidic channels 250 is curved. Specifically, the length of each microfluidic channel curves between the channel inlet 252 and the channel outlets 251, 253. In the current example, each microfluidic channel 250 defines two curves in opposite directions, meaning that each microfluidic channel 250 has a first length 254 that curves outward (or toward a first lateral direction) and a second length 256 that curves inward (or toward a second lateral direction opposite to the first lateral direction). Other curvature shapes are also possible.

[0068] Similar to the examples discussed above, in the current example, the length of each microfluidic channel is defined as an arc less than or equal to 270° or less than or equal to 200°. As can be seen, in the current design, each of these plurality of microfluidic channels 250 is nested with an adjacent microfluidic channel, which advantageously maximizes the volume of liquid flow that the substrate can accommodate. In particular, as Figure 7 As can be seen, each microfluidic channel 250 defines at least one arc along its length, which defines a concave region 258 between the channel inlet 252 and the channel outlets 251, 253, the concave region overlapping with the concave regions 258 of adjacent microfluidic channels. In the current example, each microfluidic channel is within 12 mm, 10 mm, 5 mm, 3 mm, or even 2 mm of adjacent microfluidic channels. In some embodiments, at least 50% of the length of each microfluidic channel is within 12 mm or 10 mm of adjacent microfluidic channels. In some embodiments, at least 50% of the length of each microfluidic channel is within 5 mm of adjacent microfluidic channels. In some embodiments, at least 50% of the length of each microfluidic channel is within 3 mm of adjacent microfluidic channels. In some embodiments, at least 50% of the length of each microfluidic channel is within 2 mm of adjacent microfluidic channels.

[0069] Figure 8 It is a microfluidic separator element 110 (e.g.) Figure 1 Another example (example) is a side-facing view of a substrate 620, the microfluidic separator element having a plurality of microfluidic channels 650 consistent with the technology disclosed herein. Each of the plurality of microfluidic channels 650 is generally consistent with the foregoing description of the microfluidic separator element and microfluidic channels, which is incorporated herein by reference, except as otherwise provided in the present description or Figure 8 The examples described in the text contradict each other.

[0070] The hydrodynamic separator element has a base layer 620 that defines a layer inlet 624, a plurality of first layer outlets 621, and a second layer outlet 623. The base layer 620 is typically impermeable. In the current example, the base layer 620 has a circular lateral profile, but the base layer 620 can have alternative lateral shapes. Unlike the example above, in the current example, the layer inlet 624 is directly fluidly coupled to each channel inlet 652, and therefore there is no separate inlet flow path. In the current example, the layer inlet 624 is defined by an opening in the base layer 620, which is centrally located at the center of all channel inlets 652 of the plurality of microfluidic channels 650. In some other embodiments, the layer inlet 624 may be a discrete opening, and the base may define an inlet flow path that sequentially fluidly couples the layer inlet 624 to each channel inlet 652.

[0071] The substrate 620 defines an outlet flow path 616 upstream of the second layer outlet 623. In the present example, the lateral profile of the outlet flow path 616 is circular. The length of the outlet flow path 616 is radially positioned between the plurality of microfluidic channels 650 and the outer peripheral boundary 629 of the substrate 620. The substrate 620 defines a plurality of curved microfluidic channels 650 arranged to operate in parallel. In various embodiments, the present technology includes at least six or at least ten microfluidic channels 650 in the substrate 620. Each microfluidic channel 650 defines a channel inlet 652 downstream of the layer inlet 624. Each microfluidic channel 650 defines a first channel outlet 651 upstream of the first layer outlet 621 of the plurality of first layer outlets. Each microfluidic channel 650 has a second channel outlet 653 upstream of the outlet flow path 616. In some alternative embodiments, the outlet flow path 616 may be omitted, wherein the layer outlet is the outer peripheral boundary 629 of the substrate 620, and the second channel outlet 653 extends to the outer peripheral boundary 629.

[0072] As mentioned above Figure 7 The channel inlet 652 discussed is configured to be at the component inlet 112 ( Figure 1 Downstream of ), the first channel outlet 651 is configured to be at the first element outlet 114 ( Figure 1 Upstream of ), and the second channel outlet 653 is configured to be at the second element outlet 118 ( Figure 1 The upstream of the microfluidic channel 650. These multiple microfluidic channels 650 are typically arranged to operate in parallel with respect to the liquid flow passing through the microfluidic separator element. As previously described, each of the multiple microfluidic channels 650 has an inner wall and an outer wall (with...). Figure 4 (Consistent), and each microfluidic channel 650 can be configured to enrich particles in the liquid stream toward the inner wall. The particles can be in the range of 10-20 micrometers. In some examples, the particles are eukaryotic cells, such as mammalian or insect cells.

[0073] Similar to the example discussed above, each of the plurality of microfluidic channels 650 is curved. Specifically, the length of each microfluidic channel curves between the channel inlet 652 and the channel outlets 651, 653. In the current example, each microfluidic channel 650 defines a single curve, but more complex curves could be used, such as... Figure 7The curves depicted are shown in the figure. Unlike some other examples, each microfluidic channel 650 curves in a different lateral direction. Specifically, each microfluidic channel 650 extends radially outward from the layer inlet 624 toward the outer peripheral boundary 629 of the substrate layer 620. The channel inlets 652 of the microfluidic channels 650 are circumferentially spaced around the central region of the substrate layer 620 (the layer inlet 624 in this example). The channel outlets 651, 653 are circumferentially spaced around the outer region of the substrate layer 620. Each of the plurality of microfluidic channels 650 may define the same curve, and each arc is angularly offset from the adjacent microfluidic channel 650.

[0074] Similar to the examples discussed above, in the current example, the length of each microfluidic channel is defined as an arc less than or equal to 270° or less than or equal to 200°. As can be seen, in the current design, each of these plurality of microfluidic channels 650 is nested with an adjacent microfluidic channel, which advantageously maximizes the volume of liquid flow that the substrate can accommodate. In particular, as Figure 8 As can be seen, each microfluidic channel 650 defines at least one arc along its length, which defines a concave region 658 between the channel inlet 652 and the channel outlets 651, 653, the concave region overlapping with the concave regions 658 of adjacent microfluidic channels. In the current example, each microfluidic channel is within 12 mm, 10 mm, 5 mm, or even 3 mm of adjacent microfluidic channels. In some embodiments, at least 50% of the length of each microfluidic channel is within 12 mm, 10 mm, 5 mm, or even 3 mm of adjacent microfluidic channels.

[0075] Figure 9 It is a microfluidic separator element 110 (e.g.) Figure 1 Another example of a substrate 720 (as described in the example) is shown in a side-facing view. This microfluidic separator element has a plurality of microfluidic channels 750 consistent with the technology disclosed herein. Each of these plurality of microfluidic channels 750 is generally consistent with the foregoing description of the microfluidic separator element and microfluidic channels, which is incorporated herein by reference, except as otherwise provided in the present description or Figure 9 The examples described in the text contradict each other.

[0076] The hydrodynamic separator element has a base layer 720 defining a layer inlet 724, a plurality of first layer outlets 721, and a second layer outlet 723. Unlike previous examples, here the base layer 720 defines two second layer outlets 723. The base layer 720 defines an outlet flow path 716 upstream of each second layer outlet 723. The base layer 720 defines a plurality of tortuous microfluidic channels 750 arranged to operate in parallel. In various embodiments, the present technology includes at least six microfluidic channels 750 in the base layer 720. Each microfluidic channel 750 defines a channel inlet 752 downstream of the layer inlet 724. In the current example, an inlet flow path 726 fluidly connects the layer inlet 724 and the channel inlet 752. The inlet flow path 726 may have a cross-sectional flow area that tapers along its length. Each microfluidic channel 750 defines a first channel outlet 751 upstream of the first layer outlets 721 of the plurality of first layer outlets. Each microfluidic channel 750 has a second channel outlet 753 upstream of the outlet flow path 716.

[0077] When a separator element with a base layer consistent with this example is combined with Figure 1 When using consistent components, it should be noted that each channel inlet 752 is configured to be in element inlet 112 ( Figure 1 Downstream of ), the first channel outlet 751 is configured to be at the first element outlet 114 ( Figure 1 Upstream of ), and each second channel outlet 753 is configured to be at the second element outlet 118 ( Figure 1 The upstream of the microfluidic channel 750. These multiple microfluidic channels 750 are typically arranged to operate in parallel with respect to the liquid flow through the microfluidic separator element. As previously described, each of the multiple microfluidic channels 750 has an inner wall and an outer wall (with...). Figure 4 (Consistent), and each microfluidic channel 750 can be configured to enrich particles in the liquid stream toward the inner wall. The particles can be in the range of 10-20 micrometers. In some examples, the particles are eukaryotic cells, such as the example described above.

[0078] Similar to the example discussed above, each of the plurality of microfluidic channels 750 is curved. Specifically, the length of each microfluidic channel is curved between the channel inlet 752 and the channel outlets 751, 753. Each microfluidic channel 750 has a length 754 curved toward a first lateral direction. Other curved shapes are also possible, as described above.

[0079] In the current example, the plurality of microfluidic channels 750 defined by the substrate 720 includes a first set of microfluidic channels 750a and a second set of microfluidic channels 750b. The first set of microfluidic channels 750a has channel inlets 752, which are opposite to the channel inlets 752 of the second set of microfluidic channels 750b relative to the inlet flow path 726. In the current example, the first set of microfluidic channels 750a is bent in the same lateral direction as the second set of microfluidic channels 750b. In some other embodiments, the first set of microfluidic channels 750a is bent in a different lateral direction than the second set of microfluidic channels 750b. For example, the first set of microfluidic channels 750a may be bent in the opposite lateral direction to the second set of microfluidic channels 750b. In this example, the first set of microfluidic channels 750a has a nested configuration, and the second set of microfluidic channels 750b has a nested configuration. However, the first set of microfluidic channels 750a is not nested with the second set of microfluidic channels 750b.

[0080] Similar to the examples discussed above, in the current example, the length of each microfluidic channel is defined as an arc less than or equal to 270° or less than or equal to 200°. As can be seen, in the current design, each of these plurality of microfluidic channels 750 is nested with an adjacent microfluidic channel, which advantageously maximizes the volume of liquid flow that the substrate can accommodate. In particular, as Figure 7 As can be seen, each microfluidic channel 750 defines at least one arc along its length, which defines a concave region 758 between the channel inlet 752 and the channel outlets 751, 753, the concave region overlapping with the concave regions 758 of adjacent microfluidic channels. In the current example, each microfluidic channel is within 12 mm, 10 mm, 5 mm, or even 3 mm of adjacent microfluidic channels. In some embodiments, at least 50% of the length of each microfluidic channel is within 12 mm, 10 mm, 5 mm, or even 3 mm of adjacent microfluidic channels. Example Implementation

[0081] Example microfluidic separator elements and separation components consistent with the technology disclosed herein can be advantageously combined in a variety of different systems. Figure 10 The diagram schematically depicts an example system 301, which can be combined with, for example, with Figure 1 One or more separator elements 310 are consistent. Each separator element 310 can be combined with those discussed elsewhere herein, and in particular references. Figures 2 to 9 The base layer discussed in any of the figures is consistent with the base layer. The corresponding descriptions of the separator elements and related components mentioned above are incorporated herein by reference.

[0082] In the current example, the system 301 disclosed herein can be consistent with a filter cartridge in various embodiments. In the current example system, at least one separator element 310 is positioned in series with the tangential flow filter 370. The separator element 310 is positioned upstream of the tangential flow filter 370. Positioning the separator element 310 upstream of the tangential flow filter 370 and in series with it can advantageously extend the life of the tangential flow filter 370 by mitigating fouling of the filter media 378 within the tangential flow filter 370. In the current example, the separator element 310 serves as a pre-filter for the tangential flow filter 370.

[0083] In various embodiments, separator element 310 may be a hydrodynamic separator element. Separator element 310 has an element inlet 312, a plurality of first element outlets 316, and a second element outlet 318. Although not currently visible, separator element 310 may have a plurality of tortuous microfluidic channels between element inlet 312 and the first element outlets 316. Each element inlet 312 is in direct fluid communication with and upstream of a corresponding layer inlet 324. These tortuous microfluidic channels are consistent with tortuous microfluidic channels discussed elsewhere herein. For example, each tortuous microfluidic channel may have an inner wall 144 and an outer wall 146 (…). Figure 4 In various embodiments, separator element 310 is configured to enrich particles along the inner wall. Compared to systems that enrich particles on the outer wall, such embodiments may require lower pressure drops and liquid flow rates to separate particles, which can advantageously maintain cell viability, wherein separator element 310 is configured to enrich particles (e.g., cells).

[0084] The tangential flow filter 370 can be consistent with various tangential flow filters known in the art. Typically, the tangential flow filter 370 has a feed inlet 372, a permeate outlet 376, and a permeate outlet 374. The feed inlet 372 is downstream of the first element outlet 316. Filter media 378 is disposed between the feed inlet 372 and the permeate outlet 374. As is generally known in the art, a liquid containing suspended particles flows across the surface of the filter media 378. Permeate is configured to pass through the filter media 378 to the permeate outlet 374. Permeate is configured to flow along the surface of the filter media 378 rather than through the filter media 378 to the permeate outlet 376.

[0085] Consistent with examples discussed elsewhere herein, separator element 310 may have a base layer defining a layer inlet, a plurality of first layer outlets, and a second layer outlet. The layer inlet is downstream of element inlet 312. Each first layer outlet is upstream of a first element outlet 316. The second layer outlet is upstream of a second element outlet 318. In some embodiments, each base layer may define a single microfluidic channel. In other embodiments, the base layer of each separator element 310 may define a plurality of tortuous microfluidic channels extending between element inlet 312 and each element outlet 316, 318. As described above, the plurality of tortuous microfluidic channels may extend between a first layer outlet and a layer inlet of the plurality of first layer outlets of the base layer of separator element 310. The plurality of tortuous microfluidic channels may be consistent with descriptions and appendices elsewhere herein. Figure 1 To.

[0086] In various embodiments, the system has multiple separator elements 310. These separator elements 310 are stacked with a tangential flow filter 370. Thus, each of the base layers of these separator elements 310 is also stacked. In various embodiments, the multiple separator elements 310 are stacked with the tangential flow filter 370. In various embodiments, the multiple separator elements 310 are arranged in parallel. In some examples, such as with... Figure 10 In a consistent example, each first element outlet 316 of each separator element 310 is upstream of and fluidly connected to the permeate layer outlet 336. The permeate layer outlet 336 of each separator element 310 is in fluid communication with the permeate layer outlet 336. Each permeate layer outlet 336 is upstream of and fluidly connected to the feed inlet 372 of the tangential flow filter 370. The plurality of separator elements 310 are collectively arranged in series with the tangential flow filter 370.

[0087] In some examples, each separator element 310 is a component of the separation assembly 300. Each separation assembly 300 may also have a permeate discharge layer 330 downstream of the plurality of first layer outlets 321 and the plurality of first element outlets 316 of the separator element 310. The permeate discharge layer 330 may be adjacent to the base layer, as described elsewhere herein. The permeate discharge layer 330 may extend laterally across the corresponding base layer of the adjacent separator element 310. The permeate discharge layer 330 is consistent with the figures and descriptions elsewhere herein.

[0088] In various embodiments, each separator assembly 300 is arranged in parallel with other separator assemblies 300 in system 301. In various embodiments, multiple separator assemblies 300 are stacked with a tangential flow filter 370. These multiple separator assemblies 300 and the tangential flow filter 370 are arranged in series. In some examples, such as with... Figure 10In consistent examples, the permeate discharge layer 330 has a permeate layer outlet 336 which is upstream of and fluidly connected to the feed inlet 372 of the tangential flow filter 370.

[0089] While the present example depicts three example separator assemblies 300 arranged in a stack, it should be understood that a separator system consistent with the separator system disclosed herein may include hundreds of separator assemblies 300. In some embodiments, the separator system disclosed herein has 10-30, 20-60, 50-100, or 100-200 separator assemblies 300 arranged in parallel. It should be understood that in some embodiments, each separator assembly 300 may have a height ranging from 1 mm to 10 mm or 2 mm to 5 mm.

[0090] In the current example, each second element outlet 318 of each separator element 310 is in fluid communication with the second element outlet 318 of the other separator elements 310 in system 301. Specifically, each of the separator elements 310 defines an outlet flow line 302. Each second element outlet 318 is in direct fluid communication with the outlet flow line 302. Further, in the current example, the residue outlet 376 of the tangential flow filter 370 is also in direct fluid communication with the outlet flow line 302.

[0091] In various embodiments, each separation component 300 in system 301 has a lateral profile that extends co-exists with the lateral profile of the tangential flow filter 370. In various embodiments, each separation component 300 has a configuration adapted to inclusions in the tangential flow filter cartridge assembly.

[0092] In some example embodiments, system 301 is configured to separate particles with diameters ranging from 10 to 20 micrometers from a liquid stream. In various example embodiments, system 301 is configured to separate eukaryotic cells from the liquid stream, such as the example eukaryotic cells described above. In some such example embodiments, system 301 is a component of a cell retention device in a perfusion bioreactor. Perfusion bioreactors are typically used to produce biotherapeutic agents. Figure 11 A schematic representation of such a perfusion bioreactor has been depicted and will now be described.

[0093] The perfusion bioreactor 500 typically includes a cell culture tank 510, a microfluidic separator element 410, and a tangential flow filter 470. The microfluidic separator element 410 is a component of the separation assembly 400, which is a component of the separator system 401, as referenced above. Figure 10 The separator system is described. The tangential flow filter 470 is a component of the separator system 401, and is also related to... Figure 10The description is consistent. It should be understood that in some examples, the tangential flow filter 470 and the microfluidic separator element 410 may be separate components, and in other examples, the tangential flow filter 470 and the microfluidic separator element 410 may be integrated into a single component assembly (such as a housing).

[0094] Cell culture vessel 510 is typically configured to contain liquid culture medium and cells distributed within the liquid culture medium. The cell culture vessel is typically configured to promote cell culture. Perfusion bioreactor 500 is typically configured to circulate the liquid culture medium through the system to maintain favorable culture conditions within the cell culture vessel 510.

[0095] The separator system 401 typically has a system inlet 402 configured to receive a liquid jet containing particles, such as a liquid jet containing cells. The system inlet 402 is in direct fluid communication with each element inlet 412 of each separator element 400. In some embodiments, the system inlet 402 may be an element inlet 412 of a separator element 400 as described in detail above. In the current example, the system inlet 402 is the inlet of the most upstream of the plurality of separator elements 400. In some embodiments, the liquid jet may be received from a cell culture tank 510, and in other embodiments, the liquid jet may be received from another source. In various embodiments, a pre-filter element 540 may be located upstream of the system inlet 402. The pre-filter element 540 may be a component of the separator system 401 and may be coupled to the separator element 400 upstream of the system inlet 402. In some other embodiments, the pre-filter element 540 is a separate component from the separator element 400 and may be in fluid communication with a liquid flow path upstream of the system inlet 402. The pre-filter element 540 can be specifically configured to capture relatively large particles, such as cell aggregates, which could otherwise block the liquid passage of the separator element 400.

[0096] A liquid jet can flow through each of the parallel separator elements 410. Thus, these element inlets 412 are arranged in parallel relative to the system inlet 402. Within each separator element 410, the liquid jet can flow through a plurality of parallel, tortuous microfluidic channels, as discussed above. Each of these microfluidic channels separates the liquid jet into a particle-loaded liquid jet and a particle-free liquid jet. The particle-free portion of the liquid jet can pass through each first channel outlet and each first element outlet 416, as described above. This particle-free portion of the liquid jet can exit each first element outlet 416 and enter the feed inlet 472 of the adjacent permeate discharge layer 330. The particle-free portion of the liquid jet is configured to flow through the feed inlet 472 of the tangential flow filter 470, which further separates the particle-free portion of the liquid jet into a particle-loaded liquid jet and a particle-free liquid jet. The portion of the liquid jet lacking particles is configured to flow through the permeate outlet 474 of the tangential flow filter 470 and along the flow path 520 to an external system for treatment or disposal.

[0097] As an example, the particle-loaded portion of the liquid jet can exit through a corresponding second element outlet 418 of each separator element 410. The particle-loaded liquid jet is configured to pass through the second outlet 418 of the corresponding separator element 410 to reach an outlet flow line 404, which allows the liquid jet to exit the separator system 401. Similarly, the residual liquid jet can exit the tangential flow filter 470 through a residual outlet 476. The residual outlet 476 can also be in fluid communication with the outlet flow line 404. In some such example embodiments, a cell culture tank 510 is located downstream of and in fluid communication with the tangential flow filter 470. The cell culture tank 510 can also be located downstream of and in fluid communication with each separator element 410. The cell culture tank 510 is generally located downstream of and in fluid communication with the separator system 401. The cell culture tank 510 will generally have an inlet 514 in fluid communication with the outlet flow line 404 of the separator system 401.

[0098] As described above, in some embodiments, the cell culture vessel 510 may also be located upstream of the separator system 401 in some embodiments. In such an embodiment, the cell culture vessel 510 will have an outlet 512 in fluid communication with the inlet 402 of the separation assembly 401.

[0099] In various embodiments, a liquid pump 530 is fluidly connected to the separator system 401 and the cell culture tank 510 to facilitate the flow of liquid through the system 500. Exemplary aspects

[0100] Aspect 1. A separation assembly comprising: a microfluidic separation element, the microfluidic separation element including a substrate layer, wherein the microfluidic separation element defines: an element inlet, a plurality of first element outlets defined by the substrate layer, and a second element outlet; and a permeate discharge layer adjacent to the substrate layer, wherein the permeate discharge layer is downstream of the plurality of first element outlets.

[0101] Aspect 2. The separation assembly as described in any one of Aspects 1 and 3 to 21, wherein the permeate discharge layer extends laterally across the base layer.

[0102] Aspect 3. The separation component as described in any one of Aspects 1 to 2 and 4 to 21, wherein the separation component is a part of the cell retention device of the perfusion bioreactor.

[0103] Aspect 4. The separation assembly as described in any one of Aspects 1 to 3 and 5 to 21, wherein the microfluidic separation element is a hydrodynamic separator element.

[0104] Aspect 5. The separation assembly as described in any one of Aspects 1 to 4 and 6 to 21, wherein the permeate discharge layer is defined by a mesh material.

[0105] Aspect 6. The separation assembly as described in any one of Aspects 1 to 5 and 7 to 21, wherein the permeate discharge layer is a material layer that defines microchannels downstream of the plurality of first layer outlets.

[0106] Aspect 7. The separation assembly as described in any one of Aspects 1 to 6 and 8 to 21, further comprising: a first microfluidic channel defining a channel inlet downstream of the element inlet; and a channel outlet having a first channel outlet upstream of a first element outlet among the plurality of first channel outlets, and a second channel outlet upstream of the second element outlet.

[0107] Aspect 8. The separation component as described in any one of Aspects 1 to 7 and 9 to 21, wherein the first microfluidic channel is tortuous.

[0108] Aspect 9. The separation assembly as described in any one of Aspects 1 to 8 and 10 to 21, further comprising a plurality of microfluidic channels, the plurality of microfluidic channels including the first microfluidic channel, wherein each microfluidic channel defines a channel inlet downstream of the element inlet, a first channel outlet upstream of the first element outlet among the plurality of first element outlets, and a second channel outlet upstream of the second element outlet.

[0109] Aspect 10. The separation component as described in any one of Aspects 1 to 9 and 11 to 21, wherein each of the plurality of microfluidic channels is nested with an adjacent microfluidic channel.

[0110] Aspect 11. The separation component as described in any one of Aspects 1 to 10 and 12 to 21, wherein the plurality of microfluidic channels comprises at least six microfluidic channels.

[0111] Aspect 12. The separation assembly as described in any one of Aspects 1 to 11 and 13 to 21, wherein each microfluidic channel is within 12 mm, 10 mm, 5 mm or even 3 mm of an adjacent microfluidic channel.

[0112] Aspect 13. The separation assembly as described in any one of Aspects 1 to 12 and 14 to 21, wherein each microfluidic channel is tortuous.

[0113] Aspect 14. The separation assembly as described in any one of Aspects 1 to 13 and 15 to 21, wherein each microfluidic channel defines two curves in opposite directions.

[0114] Aspect 15. The separation assembly as described in any one of Aspects 1 to 14 and 16 to 21, wherein each microfluidic channel has an inner wall and an outer wall, and each microfluidic channel is configured to enrich particles in the liquid stream toward the inner wall.

[0115] Aspect 16. The separation assembly as described in any one of Aspects 1 to 15 and 17 to 21, wherein the length of each of the plurality of microfluidic channels defines an arc of less than or equal to 270°.

[0116] Aspect 17. The separation assembly as described in any one of Aspects 1 to 16 and 18 to 21, wherein the length of each of the plurality of microfluidic channels defines an arc of less than or equal to 200°.

[0117] Aspect 18. The separation assembly as described in any one of Aspects 1 to 17 and 19 to 21, wherein the microfluidic separation element is configured to separate particles ranging from 10 to 20 micrometers from a liquid stream.

[0118] Aspect 19. The separation assembly as described in any one of Aspects 1 to 18 and 20 to 21, wherein the microfluidic separation element is configured to separate one or both of mammalian cells and insect cells in a liquid stream.

[0119] Aspect 20. The separation assembly as described in any one of Aspects 1 to 19 and 21, wherein the microfluidic separation element is configured to separate one or both of fish cells and avian cells in a liquid stream.

[0120] Aspect 21. A system comprising: a plurality of separation components as described in any one of Aspects 1 to 20, wherein the separation components are arranged in a stacked configuration; and a system inlet in direct fluid communication with each component inlet, wherein the plurality of separation components are arranged to operate in parallel.

[0121] Aspect 22. A hydrodynamic separator element comprising: a base layer defining: a layer inlet, a plurality of first layer outlets, a second layer outlet, a second outlet flow path upstream of the second layer outlet, and a plurality of tortuous microfluidic channels arranged to operate in parallel, wherein each microfluidic channel defines: a channel inlet downstream of the layer inlet, a first channel outlet upstream of the first layer outlet among the plurality of first layer outlets, and a second channel outlet upstream of the outlet flow path, wherein the base layer is impermeable, and wherein each of the plurality of microfluidic channels is nested with an adjacent microfluidic channel.

[0122] Aspect 23. The hydrodynamic separator element as described in any one of aspects 22 and 24 to 38, wherein the length of each of the plurality of curved microfluidic channels defines an arc of less than or equal to 270°.

[0123] Aspect 24. The hydrodynamic separator element as described in any one of Aspects 22 to 23 and 25 to 38, wherein the length of each of the plurality of curved microfluidic channels defines an arc of less than or equal to 200°.

[0124] Aspect 25. The hydrodynamic separator element as described in any one of Aspects 22 to 24 and 26 to 38, wherein each microfluidic channel defines two curves in opposite directions.

[0125] Aspect 26. The hydrodynamic separator element as described in any one of Aspects 22 to 25 and 27 to 38, wherein the plurality of tortuous microfluidic channels are at least six microfluidic channels.

[0126] Aspect 27. The hydrodynamic separator element as described in any one of Aspects 22 to 26 and 28 to 38, wherein each microfluidic channel is within 12 mm, 10 mm, 5 mm or even 3 mm of an adjacent microfluidic channel.

[0127] Aspect 28. The hydrodynamic separator element as described in any one of Aspects 22 to 27 and 29-38, further comprising a permeate discharge layer adjacent to the base layer, wherein the permeate discharge layer is downstream of the outlet of these first layers.

[0128] Aspect 29. The hydrodynamic separator element as described in any one of Aspects 22 to 28 and 30 to 38, wherein the permeate discharge layer extends laterally across the base layer.

[0129] Aspect 30. The hydrodynamic separator element as described in any one of Aspects 22 to 29 and 31 to 38, wherein the permeate discharge layer is defined by a mesh material.

[0130] Aspect 31. The hydrodynamic separator element as described in any one of Aspects 22 to 30 and 32 to 38, wherein the permeate discharge layer is a material layer that defines microchannels downstream of the plurality of first layer outlets.

[0131] Aspect 32. The hydrodynamic separator element as described in any one of Aspects 22 to 31 and 33 to 38, wherein the hydrodynamic separator element is a component of the cell retention device of the perfusion bioreactor.

[0132] Aspect 33. The hydrodynamic separator element as described in any one of Aspects 22 to 32 and 34 to 38, wherein each microfluidic channel has an inner wall and an outer wall, and each microfluidic channel is configured to enrich particles in the liquid stream toward the inner wall.

[0133] Aspect 34. The hydrodynamic separator element as described in any one of Aspects 22 to 33 and 35 to 38, wherein the hydrodynamic separator element is configured to separate particles ranging from 10 to 20 micrometers from a liquid stream.

[0134] Aspect 35. The hydrodynamic separator element as described in any one of Aspects 22 to 34 and 36 to 38, wherein the hydrodynamic separator element is configured to separate one or both of mammalian cells and insect cells in a liquid stream.

[0135] Aspect 36. The hydrodynamic separator element as described in any one of Aspects 22 to 35 and 37 to 38, wherein the hydrodynamic separator element is configured to separate one or both of fish cells and avian cells in a liquid stream.

[0136] Aspect 37. The hydrodynamic separator element as described in any one of Aspects 22 to 36 and 38, further comprising: a plurality of said substrate layers in a stacked configuration; and a system inlet in direct fluid communication with the inlet of each layer, wherein the plurality of substrate layers are arranged to operate in parallel.

[0137] Aspect 38. The hydrodynamic separator element of any one of aspects 22 to 37, further comprising: a permeate discharge layer adjacent to each base layer, wherein each permeate discharge layer is downstream of the corresponding first layer outlet.

[0138] Aspect 39. A system comprising: a hydrodynamic separator element having an element inlet, a plurality of first element outlets, a second element outlet, and a plurality of tortuous microfluidic channels between the element inlet and the first element outlets, wherein each tortuous microfluidic channel has an inner wall and an outer wall, and each hydrodynamic separator element is configured to enrich particles along the inner wall; and a tangential flow filter having a feed inlet downstream of the plurality of first element outlets, a permeate outlet, a permeate outlet, and a filter medium disposed between the feed inlet and the permeate outlet.

[0139] Aspect 40. The system as described in any one of Aspects 39 and 41 to 59, further comprising a cell culture vessel positioned downstream of the tangential flow filter.

[0140] Aspect 41. The system of any one of Aspects 39 to 40 and 42 to 59, wherein the hydrodynamic separator element has a base layer defining a layer inlet, a plurality of first layer outlets, and a second layer outlet, wherein the layer inlet is downstream of the element inlet, each first layer outlet is upstream of a first element outlet among the plurality of first element outlets, and the second layer outlet is upstream of the second element outlet, and wherein each of the plurality of tortuous microfluidic channels extends between the layer inlet and a first layer outlet among the plurality of first layer outlets.

[0141] Aspect 42. The system of any one of aspects 39 to 41 and 43 to 59, further comprising a permeate discharge layer adjacent to the base layer, wherein the permeate discharge layer is downstream of the outlets of these first layers.

[0142] Aspect 43. The system of any one of aspects 39 to 42 and 44 to 59, wherein the permeate discharge layer extends laterally across the base layer.

[0143] Aspect 44. The system of any one of Aspects 39 to 43 and 45 to 59, wherein the hydrodynamic separator element comprises a plurality of base layers in a stacked configuration, wherein each base layer defines a layer inlet, a plurality of first layer outlets, and a second layer outlet, and a tortuous microfluidic channel extending between the layer inlet and a first layer outlet of the plurality of first layer outlets, wherein each layer inlet is downstream of the element inlet, each first layer outlet is upstream of the first element outlet, and the second layer outlet is upstream of the second element outlet.

[0144] Aspect 45. The system of any one of aspects 39 to 44 and 46 to 59, further comprising a permeate discharge layer adjacent to each base layer, wherein the permeate discharge layer is downstream of the plurality of first layer outlets.

[0145] Aspect 46. The system as described in any one of Aspects 39 to 45 and 47 to 59, wherein each permeate discharge layer extends laterally across the corresponding basement layer.

[0146] Aspect 47. The system of any one of aspects 39 to 46 and 48 to 59, wherein the permeate discharge layer is defined by a mesh material.

[0147] Aspect 48. The system of any one of Aspects 39 to 47 and 49 to 59, wherein the permeate discharge layer is a material layer that defines microchannels downstream of the plurality of first layer outlets.

[0148] Aspect 49. The system of any one of Aspects 39 to 48 and 50 to 59, wherein each substrate layer defines a plurality of tortuous microfluidic channels, each tortuous microfluidic channel extending between the layer inlet and a first layer outlet of the plurality of first layer outlets.

[0149] Aspect 50. The system as described in any one of aspects 39 to 49 and 51 to 59, wherein each of the plurality of microfluidic channels is nested with an adjacent microfluidic channel.

[0150] Aspect 51. The system as described in any one of Aspects 39 to 50 and 52 to 59, wherein each basal layer comprises at least 6 microfluidic channels.

[0151] Aspect 52. The system as described in any one of Aspects 39 to 51 and 53 to 59, wherein, within each substrate layer, each microfluidic channel is within 12 mm, 10 mm, 5 mm or even 3 mm of an adjacent microfluidic channel.

[0152] Aspect 53. The system as described in any one of Aspects 39 to 52 and 54 to 59, wherein, within each substrate layer, each microfluidic channel is within 12 mm, 10 mm, 5 mm or even 3 mm of an adjacent microfluidic channel.

[0153] Aspect 54. The system as described in any one of Aspects 39 to 53 and 55 to 59, wherein each microfluidic channel defines two curves in opposite directions.

[0154] Aspect 55. The system of any one of aspects 39 to 54 and 56 to 59, wherein the length of each of the plurality of curved microfluidic channels defines an arc of less than or equal to 270°.

[0155] Aspect 56. The system as described in any one of aspects 39 to 55 and 57 to 59, wherein the length of each of the plurality of curved microfluidic channels defines an arc of less than or equal to 200°.

[0156] Aspect 57. The system as described in any one of Aspects 39 to 56 and 58 to 59, wherein the hydrodynamic separator element is configured to separate particles with a diameter range of 10-20 micrometers from the liquid stream.

[0157] Aspect 58. The system of any one of Aspects 39 to 57 and 59, wherein the hydrodynamic separator element is configured to separate one or both of mammalian cells and insect cells in a liquid stream.

[0158] Aspect 59. The system of any one of Aspects 39 to 58, wherein the hydrodynamic separator element is configured to separate one or both of fish cells and avian cells in a liquid stream.

[0159] It should also be noted that, as used in this specification and the appended claims, the phrase "configured as" describes a system, device, or other structure constructed to perform a particular task or employ a particular configuration. The term "configured as" may be used interchangeably with similar terms such as "arranged as," "constructed as," "manufactured as," etc.

[0160] All publications and patent applications in this specification are intended to be at the level of a person skilled in the art to which this technology pertains. All publications and patent applications are incorporated herein by reference to the extent that each individual publication or patent application is expressly and individually indicated by reference. In the event of any inconsistency between the disclosure of this application and the disclosure of any document incorporated herein by reference, the disclosure of this application shall prevail.

[0161] This application is intended to cover modifications or variations to the subject matter of this invention. It should be understood that the above description is intended to be illustrative rather than restrictive, and the claims are not limited to the illustrative embodiments set forth herein.

Claims

1. A hydrodynamic separator element, comprising: The base layer defines: Level entrance, Multiple first-level exits and second-level exits, The flow path of the second exit upstream of the second layer exit, and Multiple tortuous microfluidic channels are arranged to operate in parallel, wherein each microfluidic channel defines: The passage entrance downstream of the entrance to the layer. The first channel outlet upstream of the first-level outlet in the plurality of first-level outlets, and the second channel outlet upstream of the outlet flow path, The substrate layer is impermeable, and each of the plurality of microfluidic channels is nested with an adjacent microfluidic channel.

2. The hydrodynamic separator element according to any one of claims 1 and 3 to 14, wherein, The length of each of the plurality of curved microfluidic channels defines an arc of less than or equal to 200°.

3. The hydrodynamic separator element according to any one of claims 1 to 2 and 4 to 14, wherein, Each microfluidic channel defines two curves in opposite directions.

4. The hydrodynamic separator element according to any one of claims 1 to 3 and 5 to 14, wherein, The plurality of curved microfluidic channels are at least six microfluidic channels.

5. The hydrodynamic separator element according to any one of claims 1 to 4 and 6 to 14, further comprising a permeate discharge layer adjacent to the base layer, wherein, The permeate discharge layer is downstream of the plurality of first layer outlets.

6. The hydrodynamic separator element according to any one of claims 1 to 5 and 7 to 14, wherein, The permeate discharge layer extends laterally across the base layer.

7. The hydrodynamic separator element according to any one of claims 1 to 6 and 8 to 14, wherein, The permeate discharge layer is a material layer that defines microchannels downstream of the plurality of first-layer outlets.

8. The hydrodynamic separator element according to any one of claims 1 to 7 and 9 to 14, wherein, The permeate discharge layer is defined by a mesh material.

9. The hydrodynamic separator element according to any one of claims 1 to 8 and 10 to 14, wherein, The hydrodynamic separator element is a component of the cell retention device in the perfusion bioreactor.

10. The hydrodynamic separator element according to any one of claims 1 to 9 and 11 to 14, wherein, Each microfluidic channel has an inner wall and an outer wall, and each microfluidic channel is configured to enrich particles in the liquid stream toward the inner wall.

11. The hydrodynamic separator element according to any one of claims 1 to 10 and 12 to 14, wherein, The hydrodynamic separator element is configured to separate particles ranging from 10 to 20 micrometers from a liquid stream.

12. The hydrodynamic separator element according to any one of claims 1 to 11 and 13 to 14, wherein, The hydrodynamic separator element is configured to separate one or both of mammalian cells and insect cells in a liquid stream.

13. The hydrodynamic separator element according to any one of claims 1 to 12 and 14, further comprising: The multiple base layers are arranged in a stacked configuration; as well as A system inlet in direct fluid communication with each layer inlet, wherein the plurality of base layers are arranged to operate in parallel.

14. The hydrodynamic separator element of claim 13, further comprising a permeate discharge layer adjacent to each substrate layer, wherein, Each permeate discharge layer is downstream of the corresponding first layer outlet.

15. A detachable component, comprising: A microfluidic separation element, the microfluidic separation element comprising a substrate layer, wherein the microfluidic separation element defines: Component inlet, A plurality of first element outlets and a second element outlet defined by the substrate layer; and A permeate discharge layer adjacent to the base layer, wherein the permeate discharge layer is downstream of the outlets of the plurality of first elements.

16. The separable component as claimed in any one of claims 15 and 17 to 20, wherein, The permeate discharge layer extends laterally across the base layer.

17. The separation component as described in any one of claims 15 to 16 and 18 to 20, further comprising: A first microfluidic channel, the first microfluidic channel being defined as a channel inlet downstream of the element inlet; and a channel outlet, the channel outlet having a first channel outlet upstream of a first element outlet among the plurality of first element outlets, and a second channel outlet upstream of a second element outlet.

18. The separation component of any one of claims 15 to 17 and 19 to 20, further comprising a plurality of microfluidic channels, said plurality of microfluidic channels including the first microfluidic channel, wherein, Each microfluidic channel is defined as a channel inlet downstream of the element inlet, a first channel outlet upstream of the first element outlet among the plurality of first element outlets, and a second channel outlet upstream of the second element outlet.

19. The separable component as claimed in any one of claims 15 to 18 and 20, wherein, Each of the plurality of microfluidic channels is nested with an adjacent microfluidic channel.

20. A system comprising: Multiple separate components as described in any one of claims 15 to 19, wherein the separate components are arranged in a stacked configuration; and A system inlet in direct fluid communication with each component inlet, wherein the plurality of separate components are arranged to operate in parallel.

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