EP3268130A1 - Verfahren zum vereinigen zweier flüssigkeitsvolumina, fluidikstruktur und mikrofluidischer chip zum ausführen des verfahrens - Google Patents
Verfahren zum vereinigen zweier flüssigkeitsvolumina, fluidikstruktur und mikrofluidischer chip zum ausführen des verfahrensInfo
- Publication number
- EP3268130A1 EP3268130A1 EP16722046.6A EP16722046A EP3268130A1 EP 3268130 A1 EP3268130 A1 EP 3268130A1 EP 16722046 A EP16722046 A EP 16722046A EP 3268130 A1 EP3268130 A1 EP 3268130A1
- Authority
- EP
- European Patent Office
- Prior art keywords
- section
- flow direction
- liquid
- fluid
- narrow
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
Links
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Classifications
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
- B01L3/00—Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
- B01L3/50—Containers for the purpose of retaining a material to be analysed, e.g. test tubes
- B01L3/502—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures
- B01L3/5027—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip
- B01L3/502769—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip characterised by multiphase flow arrangements
- B01L3/502784—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip characterised by multiphase flow arrangements specially adapted for droplet or plug flow, e.g. digital microfluidics
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
- B01L3/00—Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
- B01L3/50—Containers for the purpose of retaining a material to be analysed, e.g. test tubes
- B01L3/502—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures
- B01L3/5027—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip
- B01L3/502746—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip characterised by the means for controlling flow resistance, e.g. flow controllers, baffles
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
- B01L2200/00—Solutions for specific problems relating to chemical or physical laboratory apparatus
- B01L2200/06—Fluid handling related problems
- B01L2200/0673—Handling of plugs of fluid surrounded by immiscible fluid
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
- B01L2400/00—Moving or stopping fluids
- B01L2400/04—Moving fluids with specific forces or mechanical means
- B01L2400/0403—Moving fluids with specific forces or mechanical means specific forces
- B01L2400/0406—Moving fluids with specific forces or mechanical means specific forces capillary forces
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
- B01L2400/00—Moving or stopping fluids
- B01L2400/08—Regulating or influencing the flow resistance
- B01L2400/084—Passive control of flow resistance
- B01L2400/086—Passive control of flow resistance using baffles or other fixed flow obstructions
Definitions
- the invention relates to a method for uniting two fluid volumes and a fluidic structure, in particular a microfluidic structure, for controlling one or more fluids according to the method with a fluid conduit which defines a flow direction and a cross-section bounded on all sides by walls perpendicular to the flow direction. Furthermore, the invention relates to a microfluidic chip with a substrate, a cover for the substrate and such a fluidic structure in the substrate. Finally, the invention relates to a system consisting of the fluidic structure or the microfluidic chip together with a first and a second fluid, which are combined according to the method in the fluidic structure or the microfluidic chip.
- the generic fluidic structures serve to handle in some cases very small amounts of liquid in the range of a few ml up to the ⁇ range.
- the fluid conduits in such structures have lateral dimensions less than or equal to a few millimeters. Liquids are handled in such a fluidic structure in the flow system, ie conveyed by generating a pressure difference (positive and / or negative pressure) through the fluid lines.
- a pressure difference positive and / or negative pressure
- 5,972,710 A discloses a fluid structure having a diffusion channel with a V-shaped profile, in which an analyte and a detection liquid are combined to form a parallel laminar flow in order to detect particles in the analyte by means of diffusion processes.
- US 2011/0100476 A1 discloses a microfluidic structure with a valve formed from a fusible structure within a fluid channel.
- the refractable structure serves to permanently close the fluid channel with external energy supply.
- a valve of a microfluidic system which comprises a fluid channel with an obstacle.
- the obstacle is formed of a smart polymer that undergoes a volume change with external energy input, thereby changing the flow of fluid through the channel.
- US 2013/0167958 A1 deals with microfluidic structures in fluidic logic circuits.
- the microfluidic structures include, inter alia, branch circuits for controlling gas or liquid bubbles in a carrier medium.
- the document US 2004/0195539 A1 describes a microfluidic valve of a fluid line, which is formed in a substrate in the form of a channel and has a channel constriction at the location of the valve.
- the channel is closed with a self-adhesive cover film.
- the valve is opened in the initial state and can be permanently closed by pressing the self-adhesive film in the area of the constriction. Furthermore, it is described how this valve is subsequently formed by the deformation of the substrate material in the Area of the channel narrowing can be opened by means of a stamping stamp from outside.
- the document US 2007/0286774 A1 deals with a microfluidic device with a fluid channel, which is formed in a substrate and covered with a foil.
- a fluid channel which is formed in a substrate and covered with a foil.
- the channel at least 2 sections are formed, in which a liquid flows in due to a capillary effect.
- the two sections are spaced apart so that the capillary flow is interrupted therebetween.
- fluid line structures which have at least two fluidic supply lines and one outlet, which meet in the region of a T-junction. It is difficult to ensure that liquid columns of limited volumes, also referred to as "liquid plugs", also arrive at the T-junction from the two supply lines for the purpose of unification at the same time.
- liquid plugs also arrive at the T-junction from the two supply lines for the purpose of unification at the same time.
- Liquid control columns are required to control the delivery pressure to control the position of the fluid columns, for example by means of a photocell which measures exactly where the beginning and end of both fluid columns are located.
- keitsklalen be included, which always separate the liquid columns within the fluid lines from each other. In the case of a separation of the liquid columns by air bubbles, for example, a complete mixing of liquids is prevented, or it will interfere with the functionality of sensory devices.
- the basic aim is to limit the control or regulation to a necessary minimum.
- the microfluidic structure described therein comprises a fluid conduit that expands at a location lateral to the flow direction to a fluid chamber.
- the widening and surface area of the fluid chamber are such that a first volume of liquid passed through the fluid chamber is distributed over the entire cross section of the fluid chamber.
- a further supply line opens into a holding position in the fluid chamber, which is designed such that a second liquid volume transported there remains in the region of the holding position until it is received by the first liquid volume passed through and both liquid volumes are conveyed out of the fluid chamber together.
- this structure provides an alternative, passive fluid control which eliminates complex valve circuits and / or other active fluid control.
- microfluidic structure comprises only one feed line and a Discharge for the handling of two or more separately supplied liquid columns (plugs). These are separated by the supply line and by gas bubbles also supplied to a laterally expanded fluid chamber whose volume is in any case greater than the volume of the first incoming liquid column.
- the fluid chamber is formed so that the liquid wets only one of the opposite side walls. As a result, a bypass is released, through which the gas can escape from the gas buffer between the liquid columns.
- the second liquid column thus collects the first liquid, which is still adhering to the side wall, and together with the latter, is conveyed out of the fluid chamber.
- this requires as a further condition that the total volume of both fluids be sufficient to wet both walls of the expanded union chamber.
- the object is achieved by a method having the features of claim 1, a fluidic structure having the features of claim 3, a microfluidic solved chip with the features of claim 16 and a system having the features of claim 21.
- the fluid line of the aforementioned fluidic structure has a holding section which is expanded in the flow direction and free of further supply and discharge lines, in which the fluid line has a narrow area and, with respect to the flow direction, a wide area laterally adjacent, the narrow area being at least a first direction perpendicular to the flow direction (first lateral direction) has a smaller wall distance he J than the minimum wall distance h w of the wide range.
- the object is also achieved by a microfluidic chip of the type mentioned, in which the fluid conduit is formed in the form of a channel in the substrate and closed by the cover, wherein the channel is divided in the holding portion in the narrow and the wide range.
- the wide area has a greater channel depth than the narrow area.
- the first lateral direction is perpendicular to a channel base opposite the cover, ie the wall distance h e of the narrow region is determined by the channel depth.
- the holding section is thus generally longitudinally subdivided into two fluidically connected regions which are adjacent to one another and which are narrower than the other in any spatial direction.
- This configuration ensures that a first liquid, which wets the walls of the fluid line weaker or more wetted than the buffer medium surrounding this liquid and reaches the holding section, there securely held in both cases due to capillary forces.
- a first liquid which wets the walls of the fluid line weaker or more wetted than the buffer medium surrounding this liquid and reaches the holding section, there securely held in both cases due to capillary forces.
- the holding section has as a section of the fluid line only a supply line and a discharge in the form of the fluid line itself.
- Two or more liquid columns are the holding section, separated by one or more buffer media, fed through the same supply line and after union in the holding section by the same derivation together removed the holding section.
- a second condition is accordingly, quite similar to the fluid chamber in the above-mentioned article, that the holding area is sufficient to completely accommodate the expected volume V F n of the first liquid arriving there. In other words, it is required that the volume V F n of the first liquid is smaller than the volume of the holding portion.
- the term "holding area" refers to either the narrow or the wide area of the holding section, depending on where the liquid is located, depending on its wetting behavior The volume of the holding area can therefore be the volume V e of the narrow area of the holding section .
- first liquid, the walls of the fluid line more wet than the surrounding buffer medium Then the following must apply:.
- VFH ⁇ V e the volume of the holding area can also be the volume V w of the wide range of the retaining portion when the first liquid, the walls of the fluid conduit weaker
- VFH ⁇ V w Only under these conditions does the first liquid release the beginning and the end of the laterally adjacent region of the holding section, so that a bypass line for a between the first liquid and a liquid passes therethrough the following second liquid enclosed Pufferme ⁇ dium is released.
- a third condition is quite similar to the known solution in that the expected total volume of the two or more combined liquids V F ii + V F12 is sufficient to seal one end of the holding portion with liquid.
- the total volume of the combined liquids VFH + V F12 be larger than the volume of the holding portion.
- the volume V w of the wide range of the holding section V F n + V F i2> V w .
- V F i2 hereby represents in each case the volume of a second liquid or a plurality of second liquids In this way, a total of two, three or more liquids separated by buffer media can be combined in the holding region and subsequently the entire combined liquid volume under continued delivery pressure be automatically conveyed out of the holding area of the fluid line.
- these conditions are also reflected in the system according to the invention, which comprises a fluidic structure or a microfluidic chip of the type described above, a first liquid with a defined volume VFM, and a second liquid with a defined volume VFI2 and a buffer medium, which is at the beginning of the holding region between the first and second fluids and transportable along with the first and second fluids through the fluid conduit, wherein optionally the first and second fluids wet the walls of the fluidic structure more than the buffer medium and the conditions are VFH ⁇ V e and VFM + V F i2> V e , or wherein the first and the second liquid wetting the walls of the fluidic structure weaker than the buffer medium and wherein the conditions are: V F n ⁇ V w and V F n + V F i2> V w .
- the liquids are more strongly wetting liquids means that the liquid surface forms a contact angle to the surface of the channel of ⁇ 90 °, preferably ⁇ 75 ° and particularly preferably ⁇ 45 °. Conversely, the liquids are called liquids with weaker wetting when the liquid surface has a contact angle to Surface of the channel of> 90 °, preferably> 105 ° and particularly preferably> 135 ° form.
- Liquid surface is the interface of the first and second liquids to the adjacent buffer medium. In the case of an interface to a gaseous buffer medium, one would speak for simplicity of wetting or non-wetting first and second liquids.
- the buffer medium is generally referred to as a medium which is insoluble in the first and in the second liquid.
- This may just be a gas, such as air, or a liquid, such as an oil-based liquid, if the first and second water-based liquids, or, conversely, a water-based liquid, if the first and second oil-based fluids are based.
- reaction mixtures for molecular biological reactions may be mentioned in which nucleic acids are supplied as the first liquid and enzymes as the second liquid of the fluidic structure according to the invention in aqueous liquid volumes and combined therein according to the method in order to allow a reaction.
- a buffer medium mineral come c oils, silicone oils, fluorinated oils, or organic polymers (for example, "Novec 7500” (hydrofluoroether (C7F150C2H5)) into consideration.
- a lateral transition is formed between the narrow region and the wide region in the form of a step which extends in the direction of flow.
- One or more such shoulders may rise from one or more walls delimiting the fluid conduit.
- the narrow region is preferably formed in each case between a plateau of the shoulder and an opposite wall section, wherein the first lateral direction is perpendicular to the plateau.
- the heel may have sharp or rounded or chamfered edges.
- a preferred embodiment of the invention provides that the fluid line in the flow direction before the Garäbrough an inlet portion and in the flow direction behind the holding portion has an outlet portion, wherein the inlet portion and the outlet portion in the first lateral direction steplessly in the narrow region of the holding portion or in the wide Go over the area of the holding section.
- the channel bottom in the inlet section and in the outlet section passes continuously into the channel bottom of the narrow area or into the channel bottom of the wide area.
- the channel bottom of the narrow area preferably forms the above-mentioned plateau.
- “Infinitely” comprises, on the one hand, a transition from the inlet section to the narrow region of the holding section and from there to the outlet section without cross-sectional change in the first lateral direction This is achieved, for example, in one embodiment in that the inlet section and the outlet section are vertical in the first direction to the flow direction in each case have a wall distance h in or h out , which is equal to the minimum wall distance h e of the narrow range.
- the dimension of the fluid conduit in the first lateral direction does not change as it flows through the narrow area in the holding portion.
- the wide area of the holding section forms in this embodiment, however an expansion of the cross section of the fluid conduit in the first lateral direction.
- stepless also encompasses a continuous transition between the sections, where “continuous” refers to a continuous, non-erratic change in cross-section.
- the inlet section accordingly in the first lateral direction a distance from the wall toward> h e, wherein the fluid line has in the flow direction after the inlet portion and above the holding portion has a first transition section in which the lateral distance from the wall in the flow direction of H in at h e constantly rejuvenated.
- the outlet section has a wall distance h out > h e in the first lateral direction, the fluid line having a second transition section in the flow direction behind the holding section and in front of the outlet section, in which the lateral wall spacing in the flow direction from h e to h ou t constantly expanding.
- the channel cross section of the fluid line tapers in the first lateral direction on the inlet side towards the holding section to the wall distance of the narrow area and widens again on the outlet side in a corresponding manner.
- the narrow area thus forms a narrowing of the line cross-section.
- an advantageous embodiment of the invention provides that the fluid line in the holding section in a second direction perpendicular to the flow direction (second lateral direction) relative to the inlet section and the outlet section laterally expanded.
- a second advantage of the expansion is that larger liquid Volume can be handled without the space requirement of the structure on the microfluidic chip increases too much. In contrast, a correspondingly elongated channel would require more space even when meandering.
- the fluid conduit can be widened on the side of the narrow region, on the side of the wide region or on both sides in the second lateral direction.
- the wide region is arranged offset in the second direction perpendicular to the flow direction with respect to the inlet section and / or with respect to the outlet section.
- This embodiment has the advantage that the flow of the fluids is less strongly or not deflected when passing through the narrow region in the holding section, so that the risk of turbulence is reduced.
- a further advantageous embodiment of the invention provides that the fluid line has at least one stop structure in front of and / or behind the holding section in the flow direction.
- the at least one stop structure is preferably designed in the form of a shoulder interrupting the course of at least one of the walls of the fluid line.
- Paragraphs in this sense form one or more molds in the at least one wall of the fluid conduit or one or more projections along the at least one wall of the fluid conduit or both.
- the hollow mold can be formed for example by a laterally outgoing channel or a recess.
- a plurality of protrusions may be one forming a comb-like structure. It is crucial in all cases that the stop structure can not be overcome solely by utilizing capillary forces. The stop structure thus prevents the first liquid from shooting over the end thereof as it flows into the holding portion or being drawn back into the inlet portion by the capillary forces. In this way it supports the holding function of the narrow area and makes the flow process during the merging of two liquids even more reliable.
- Figure 1 a-c a first embodiment of the invention in three views
- Figure 2a-c shows a second embodiment of the invention in three views
- Figure 3a-c shows a third embodiment of the invention in three views
- Figure 4a-e a fourth embodiment of the invention in five views
- FIG. 5a-c three snapshots in the holding portion of the fluidic structure according to Figure 1 inflowing liquid
- Figure 6 shows a fifth embodiment of the invention with an alternative embodiment of the stop structures in front of the holding section
- Figure 7 shows a sixth embodiment of the invention with an alternative embodiment of the paragraph between the narrow region and the wide portion of the holding portion;
- Figure 8 shows a seventh embodiment of the invention with an alternative embodiment of the shoulder between the narrow region and the wide region of the holding section;
- FIG. 9a-c an eighth embodiment of the invention in three views
- Figure 10a-c a ninth embodiment of the invention in three views
- FIG 11 a-c three snapshots in the holding portion of the fluidic structure according to Figure 9 inflowing liquid.
- FIG. 1 a shows a plan view of a first embodiment of the invention.
- FIG. 1b shows a longitudinal section and
- FIG. 1c shows a cross section in each case at the positions indicated in FIG. 1a.
- Shown is a substrate 10 of a schematically greatly simplified microfluidic chip, in which only one fluid line 12 is formed in the form of a channel.
- a fluid not shown, flows through the fluid line 12 under pressure in the direction indicated by the arrow 13, also referred to as flow or longitudinal direction.
- the fluid line or the channel have a transverse to the flow direction on all sides bounded by walls in cross-section. This is limited in a first direction perpendicular to the flow direction by a channel bottom 14 and the cover, not shown, at the position opposite the channel bottom 16.
- microfluidic chips usually have a plurality of fluid lines and functional elements, such as reaction chambers, mixer structures, valves or the like. Furthermore, the channel is closed on its open upper side by means of a film laminated to the substrate, namely that cover. In FIGS. 1 a to 1 c, the representation of the cover has been omitted in order to simplify matters.
- the channel 14 is functionally divided into an inlet section 18 in the flow direction, a holding section 20 downstream and an outlet section 22 further downstream.
- the holding section 20 is laterally, ie transversely to the flow direction, subdivided into a narrow region 24 and laterally adjacent thereto a wide region 26.
- the fluid conduit has in the narrow region 24 in a first lateral direction between the channel bottom 14 and the cover (position 16) a wall distance h e , which in this case is determined by the channel depth.
- the minimum wall distance of the wide region 26 is designated by h w and extends in another lateral direction in the example shown.
- the distance h e is smaller than the minimum wall distance h w of the wide range.
- the channel depth in the wide area that is greater than or equal to the minimum wall distance h w must also be greater than the channel depth in the narrow area.
- the inlet section in the first lateral direction a wall distance h and the outlet portion 22 having a wall distance h ou t and both h and hout are the same as the wall distance h e in the narrow region of the holding section 20.
- the inlet section 18 and the outlet section 22 thus pass continuously into the narrow region 24 in the first lateral direction.
- the channel groove 14 continues in the inlet and outlet portions and in the narrow portion 24 of the holding portion 20.
- the wide region 26 forms a depression starting from the channel bottom 14.
- the total depth of the wide region 26 is even greater than its width, which in this example defines the minimum wall distance h w .
- a lateral transition in the form of a step 28 which extends in the direction of flow is formed between the narrow region 24 and the wide region 26.
- the shoulder 28 in turn has a sharp edge 29 in this embodiment.
- a sharp edge offers greater process reliability, since a greater amount of energy has to be expended here in order to allow the liquid to flow over the edge.
- the contact angle hysteresis which ensures that the contact lines formed by the interface and the wall stick to edges and kinks.
- FIGS. 2a to 2c show a second schematically greatly simplified embodiment of the fluidic structure according to the invention.
- a fluid line 32 is formed in the form of a channel which extends in a first lateral direction from the channel bottom 34, 34 'and is closed on its upper side 36 by a cover or film, not shown.
- the fluid line 32 has in succession an inlet section 38, a first transition section 39, a holding section 40, a second transition section 41 and downstream an outlet section 42.
- the holding section 40 is in turn subdivided laterally into a narrow region 44 and laterally adjacent thereto a wide region 46.
- the wide portion 46 starting from the level of the channel bottom 34 in the narrow portion 44, a recess, so that the lateral transition between the narrow portion 44 and the wide portion 46 in the form of a directionally extending paragraph 48 with sharp edge 49th is trained.
- the wall distance between the channel bottom 34 'and the top 36 in the inlet section is greater than the wall distance h e in the narrow section 44 of the retaining section 40. This is due to a difference in level of the channel bottom, which is bridged in the transition section 39 by a ramp-like channel bottom 35. In other words, thereby the wall distance tapers in the flow direction 13 from towards h e steadily.
- the wall distance h ou t of the outlet section 42 is greater than the wall distance h e of the narrow range and also serves the second transition portion 41 with the ramp-like channel bottom 35 'to compensate for the level difference or the wall distance in the flow direction in the second transition section 41st from h e to h ou t steadily expand.
- the inlet section 38 and the outlet section 42 merge into the narrow region 44 of the holding section 40 in the flow direction without any offset. From the point of view of the flowing fluid, the narrow region 44, starting from the cross section of the inlet section 38, thus forms a significant cross-sectional constriction, which leads to an increase in the flow velocity with constant volume delivery.
- this embodiment comprises a microfluidic chip with a substrate 60 into which the fluid conduit 62 is incorporated in the form of a channel.
- the fluid flowing in the direction of flow 13 first flows once again through an inlet section 68, followed by a first transition section 69, then the holding section 70, then the second transition section 71 and finally downstream the outlet section 72.
- the holding section 70 is again laterally in a narrow region 74 a wall distance h e in a first lateral direction and an adjacent wide region 76 with a minimum wall distance h w in the longitudinal direction divided. Again, h e ⁇ h w .
- the wall distance h in the inlet section 68 and the wall distance hout in the outlet section 72 are greater than the wall distance h e in the narrow region 74 of the holding section 70.
- the first and second transition sections 69 and 71 are each provided with a ramp-like channel bottom 65, 65 ', which form a heelless transition.
- the fluid line 62 is laterally expanded in the holding section 70 in a second direction perpendicular to the flow direction 13 with respect to the inlet section 68 and with respect to the outlet section 72.
- the lateral extension is configured symmetrically with respect to the center axis of the fluid line 64, while the wide region 76 is located in the second lateral direction on an edge of the fluid line 62, as in the two preceding examples. det.
- the fluid line 62 is widened both on the side of the narrow region and on the side of the wide region in the second lateral direction.
- the lateral expansion benefits primarily the narrow region 74 by being wider in the second direction than the inlet and outlet sections.
- the cross-sectional loss due to the taper in the first lateral direction from h in to h e can thus be partially compensated and the flow velocity in the narrow region 74 lowered at a constant volume flow.
- the wide portion 76 is offset from the inlet portion 68 in the second lateral direction and offset from the outlet portion 72. He is so broad that he finds room in the bulge formed by the extension.
- the lateral transition or shoulder 78 between the narrow region 74 and the wide region 76 which extends in the direction of flow 13 therefore lies in alignment with a lateral wall 79 of the fluid line 62 in the inlet section 68 and in the outlet section 72. This causes the flow of the fluid when passing the narrow portion 74 in the holding portion 70 is deflected less total. The danger of turbulence is therefore considerably reduced by the configuration of the extension.
- FIG. 4 shows a further refinement of the fluidic structure.
- the fluid conduit 82 is formed in the form of a channel.
- the fluid line 82 has, in the flow direction 13, an inlet section 88, a first transition section 89, a holding section 90, a second transition section 91, and downstream an outlet section 92.
- the holding portion 90 is in turn laterally in a narrow region 94 and laterally adjacent thereto in a wide range 96 divided.
- the wide region 96 starting from the level of the channel bottom 84 in the narrow region 94, forms a depression, so that the lateral transition between the narrow region 94 and the wide region 96 in the form of a sharp edge 98 in the flow direction 13 99 is formed.
- the relevant wall distance h e of the narrow region 94 is determined by the channel depth.
- the direction of the minimum wall distance h w in the wide region 96 coincides with the first lateral direction.
- the minimum wall distance h w in the wide area 96 is also determined by the channel depth there. It also applies here according to the invention: h e ⁇ h w .
- the lateral expansion of the fluid line in the transition sections and the holding section serves, as before, to at least partially compensate for a lateral narrowing of the line cross section in the narrow region and thus to lower the flow velocity here.
- the wide area 96 in this embodiment is again positioned so that the shoulder 98 forming the lateral transition to the narrow area 94 is in alignment with the side wall 100 of the inlet and outlet sections.
- the walls 01, 102 have rounded or "continuously differentiable" contours in the first transition section 89, holding section 90 and second transition section 91. This favors the flow and prevents the formation of turbulence at the section transitions Moreover, such continuous contours minimize the holding forces on the contact line between the liquid-gas interface and the surface of the channel (solid), as already discussed above with reference to the sharp edge 29 in Figure 1.
- the further area is a little more complex in this embodiment than before. It has approximately the shape of a walking stick with a "handle" at the outlet end of the holding section facing away from the narrow area 94. As a result, this end of the wide area 96 forms a dead end 104. This has proven to be very advantageous If a gas cushion trapped at the dead end 104 prevents the liquid from completely wetting over the entire area, a boundary surface will always remain here, which is the starting point for liquid separation and thus ensures complete emptying of the wide area.
- stop structures 105, 106 in the opposite walls 101 and 102 of the fluid line 82 in front of the holding portion 90.
- the stop structures 105, 106 are formed as a hollow shape, more precisely as dead channels, in the two walls 101, 102 and interrupt the Course of the same such that a flowing in the narrow portion 94 of the holding portion 90 fluid does not flow back into the inlet portion 98 due to capillary forces.
- FIGS. 5a to 5c show a sequence of a fluid flowing into the fluidic structure according to FIG. All three snapshots show the same section of the microfluidic chip 110 shown schematically in greatly simplified form with the substrate 120, in which the fluid line 122 is incorporated in the form of a channel.
- a cover 125 in the form of a film is shown, which closes the laterally open on one side channel.
- the fluid line 122 is shown cut in the region of the holding section, in which it has a narrow region 134 with a smaller channel depth and laterally adjacent a wide region 136 with a larger channel depth.
- a first fluid 140 flowing in the direction 13 has a front front or interface 142, which is still in the inlet section at the point in time according to FIG. 5a.
- the first fluid 140 has advanced further, so that its rear boundary surface 144 can already be seen in the inlet section.
- the first fluid 140 forms a so-called fluid column.
- the front interface has already reached the holding portion of the fluid conduit and enters the flat area 134 due to capillary forces while not wetting the wide area 136.
- a buffer medium 146 which spatially separates the first fluid 140 from a subsequent second fluid 150, which appears in the inlet section in FIG. 5c. Due to the further progress of both fluid columns, the rear interface 144 of the first liquid column 140 eventually arrives at the beginning of the wide region 136 of the holding section. At this point, the rear boundary surface 144 of the first liquid column 140 tears off the wall of the fluid channel 122 at which the wide region 136 is located. The wide area 136 then releases a bypass line, through which the medium from the buffer 146, a (e) in the first and in the second fluid insoluble gas or liquid, can escape, as the arrow 152 symbolizes. Meanwhile, the first fluid column 140 remains in the holding area because it no longer feels any delivery pressure.
- the subsequent liquid column 150 can be transported further in the direction of the first liquid column 140 until both liquid columns are combined. Then both will be promoted together.
- This can either be arranged so that the combined liquid column completely around Air cushion runs around in the bypass line or that it first empties the bypass line and only then completely leaves the holding area. The process depends on details of the shape of the transition sections.
- FIG. 5 shows the system with a fluidic structure or with a microfluidic chip, in which the narrow region 134 has a volume V e , with a first liquid 140 having a defined volume V F n, with a second liquid 150 a defined volume VFI2, and with a buffer medium 146, which is arranged at the beginning of the holding region between the first and the second liquid and transportable together with the first and the second liquid through the fluid line 122, wherein the first and the second liquid 140, 50 the Walls of the fluidic structure more wet than the buffer medium 146 and the conditions are: VFH ⁇ V e and VFH + V F i2> V e .
- the buffer medium 146 may be, for example, gas or oil when the fluids 140 and 150 are water-based and the wall of the fluid conduit is hydrophilic.
- FIG. 6 shows an alternative embodiment of a fluidic structure, which corresponds in terms of the shape of the fluid line 158 to that of FIGS. 1 and 5.
- the only difference is a stop structure 160, which has a plurality of projections 162 along a wall or, more precisely, the channel bottom 163 of the fluid line.
- the projections 162 together form a comb-like structure at the end of the narrow region 164. This generally obstructs the flow of a wetting liquid and thus in particular prevents it from accidentally flowing back from the narrow region of the holding section into the outlet section of the fluid line.
- FIG. 7 shows a simplified microfluidic chip 170 with an alternative embodiment of the fluid line 172, more precisely the one forming the lateral transition between the narrow region 174 and the wide region 176 Flow direction extended paragraph 178.
- the paragraph 178 has, in contrast to all embodiments shown above, no sharp, but a rounded edge 180.
- the paragraph 178 is also in the channel bottom 182 of the wide area 176 in the form of a rounding 184 over.
- the transition therefore has a curved cross-section without a jump or crease, with the effect that the wall distance from the narrow region 174 in the lateral direction to the wide region 176 increases in a continuously differentiable form.
- FIG. 8 shows a simplified microfluidic chip 90 with a further alternative embodiment of the fluid line 192, more precisely of the shoulder which forms the lateral transition between the narrow region 194 and the wide region 196 and extends in the flow direction.
- the wall distance h e of the narrow region 194 as well as the minimum wall distance h w of the wide region 196 are again determined by the respective channel depth and the shoulder has a rounded edge and in the transition from the channel base 202 of the wide region 196 in paragraph 198 a rounding on.
- the wide region 196 starting from the channel base 203 in the narrow region 196, does not form a depression.
- FIG. 9 a shows, analogously to FIG. 1 a, a plan view of a further embodiment of the invention.
- FIG. 9b shows a longitudinal section correspondingly and
- FIG. 9c shows a cross section in each case at the positions indicated in FIG.
- FIG. 9a Shown is a substrate 310 of a schematically greatly simplified microfluidic chip, in which only one fluid line 312 is formed in the form of a channel. An unillustrated fluid flows through the fluid line 312 under pressure in the direction indicated by the arrow 13.
- the fluid line or the channel have a transverse to the flow direction on all sides bounded by walls in cross-section. This is limited in a first direction perpendicular to the flow direction by a channel bottom 314 and a cover, not shown, at the position opposite the channel bottom position 316.
- the channel 312 is again functionally divided into an inlet section 318 in the flow direction, a holding section 320 downstream and an outlet section 322 further downstream.
- the holding portion 320 is laterally, ie transversely to the flow direction 13, in a narrow region 324 and laterally adjacent to a wide portion 326 divided.
- the fluid conduit has in the narrow region 324 in a first lateral direction between the channel bottom 314 and the cover (position 316) a wall distance h e , which in this case is determined by the channel depth.
- the minimum wall distance of the wide region 326 is designated by h w and extends in another lateral direction in the example shown.
- the distance h e is smaller than the minimum wall distance h w of the wide range.
- This condition alone is decisive for the inflow into the holding section. Due to capillary forces in the narrow region 324 or a less wetting liquid flowing into the holding section, the better wetting liquid is held in the wide region 326. It is also not decisive here whether wall distances are compared in the same or different directions. It is also not important whether the narrow area in the second lateral direction is wider or narrower than that of the minimum wall distance h w of the wide area.
- the channel depth in the wide region 326 is greater than its width, which in this example defines the minimum wall distance h w .
- inlet portion 318 and outlet portion 322 h perpendicular to the channel base 314 in the first lateral direction wall clearances have in or h ou t corresponding to the channel depth in the wide portion 324 of the holding portion 420th
- the inlet section 318 and the outlet section 322 thus transition continuously into the wide area 324 in the first lateral direction.
- the channel bottom 314 continues in the inlet and outlet section and in the wide region 324 of the holding section 320.
- the narrow region 326 forms a lateral transition in the form of a step 328 extending in the flow direction 13 from the channel base 314.
- the shoulder 328 again has a sharp edge 329 in this exemplary embodiment.
- FIGS. 10a to 10c a plan view, a longitudinal section and a cross section of a further embodiment of the invention are shown analogously to FIGS. 9a to 9c.
- the substrate of a schematically highly simplified microfluidic chips is designated by 410, in which only one fluid line 412 is formed in the form of a channel.
- An unillustrated fluid flows through the fluid line 412 pressure-operated in the direction indicated by the arrow 13.
- the fluid line or the channel have a transverse to the flow direction on all sides bounded by walls in cross-section. This is limited in a first direction perpendicular to the flow direction by a channel bottom 414 and a cover, not shown, at the channel base 414 opposite position 416.
- the channel 412 is again functionally divided into an inlet section 418 in the flow direction, a holding section 420 downstream and an outlet section 422 further downstream.
- the holding portion 420 is laterally, ie transversely to the flow direction 13, in a narrow region 424 and laterally adjacent to a wide region 426 divided.
- the fluid line 412 is laterally expanded in the holding section 420 analag to the example in FIG. 3 in a second direction perpendicular to the flow direction 13 with respect to the inlet section 418 and with respect to the outlet section 422.
- the wide region 426 is located in the second lateral direction at an edge of the fluid line 412 and is therefore arranged offset in the second lateral direction relative to the inlet section 418 and opposite to the outlet section 422.
- the lateral expansion again benefits the narrow region 424, which is wider in the second direction than the inlet and outlet sections.
- the cross-sectional loss due to the taper in the first lateral direction from h e to e can thus be partially compensated and the flow velocity in the narrow region 424 lowered at a constant volume flow.
- the fluid conduit has in the narrow region 424 in a first lateral direction between the channel bottom 414 and the cover (position 416) a wall distance h e determined by the channel depth.
- the minimum wall distance of the wide region 426 is indicated by h w and extends in another, second lateral direction.
- the distance h e is smaller than the minimum wall distance h w of the wide range.
- This condition alone is critical in keeping a better wetting liquid flowing into the holding portion into the wide region 426 due to capillary forces in the narrow region 424 or a less wetting liquid flowing into the holding portion. It is also not decisive here whether wall distances are compared in the same or different directions. It is also not important whether the narrow area in the second lateral direction is wider or narrower than that of the minimum wall distance h w of the wide area.
- the channel depth in the wide region 426 is greater than its width, which in this example defines the minimum wall distance h w .
- the inlet section 318 and the outlet section 422 perpendicular to the channel base 414 in the first lateral direction have wall distances h in and h out corresponding to the channel depth in the wide region 424 of the holding section 420.
- the inlet portion 418 and the outlet portion 422 thus go in the first lateral direction steplessly in the wide range 424 over.
- the channel bottom 414 continues in the inlet and outlet section and in the wide region 424 of the holding section 420.
- the narrow region 426 again forms a lateral transition in the form of a step 428 which extends in the direction of flow 13 starting from the channel bottom 414.
- the shoulder 428 again has a sharp edge 429 in this exemplary embodiment.
- FIGS. 11 a to 1 c show, analogously to FIGS. 5 a to 5 c, a sequence of a fluid flowing into the fluidic structure, this time the fluidic structure according to FIG. 9. All three snapshots show the same section of the microfluidic chip 510 shown schematically in greatly simplified form with the substrate 520, in which the fluid line 522 is incorporated in the form of a channel.
- a cover 525 is shown in the form of a film, which closes the laterally open on one side channel.
- the fluid line 522 is shown cut in the region of the holding section, in which it has a narrow region 534 with a smaller channel depth and laterally adjacent a wide region 536 with a larger channel depth.
- a first fluid 540 flowing in the direction 13 has a front front or boundary surface 542 which is still in the inlet section at the point in time according to FIG. 11 a.
- the first fluid 540 has advanced further, so that its rear boundary surface 544 can already be seen in the inlet section.
- the first fluid 540 forms a so-called fluid column.
- the front interface 542 has already reached the holding portion of the fluid conduit and enters the wide area 536 due to capillary forces, while entering the narrow area 534 avoids.
- the capillary forces act in this case due to reverse wetting behavior opposite to those in Figure 5.
- a buffer medium 546 which spatially separates the first fluid 540 from a subsequent second fluid 550, which appears in the inlet section in FIG. 11c.
- the rear boundary surface 544 of the first liquid column 540 arrives at the beginning of the wide region 536 of the holding section.
- the rear interface 544 of the first liquid column 540 ruptures from the wall of the fluid channel 522 at which the narrow region 534 is located.
- the narrow area 534 then releases a bypass line, through which the medium can escape from the buffer 546, as the arrow 552 symbolizes. Meanwhile, the first fluid column 540 remains in the holding area because it no longer feels any delivery pressure.
- the subsequent liquid column 550 can be transported further in the direction of the first liquid column 540 until both liquid columns are united. Then both will be promoted together.
- This can either be arranged so that the combined liquid column runs completely around an air cushion in the bypass line or that it first empties the bypass line and only then completely leaves the holding area. The process depends on details of the shape of the transition sections.
- the example in FIG. 11 is the system with a fluidic structure or with a microfluidic chip, in which the wide region 536 has a volume V w , with a first fluid 540 with a defined volume V F n a second liquid 550 having a defined volume V F
- the buffering medium 546 may be, for example, gas or oil when the fluids 540 and 550 are water-based and the wall of the fluid conduit is hydrophobic.
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DE102015204235.9A DE102015204235B4 (de) | 2015-03-10 | 2015-03-10 | Fluidikstruktur mit Halteabschnitt und Verfahren zum Vereinigen zweier Flüssigkeitsvolumina |
PCT/EP2016/000429 WO2016142067A1 (de) | 2015-03-10 | 2016-03-10 | Verfahren zum vereinigen zweier flüssigkeitsvolumina, fluidikstruktur und mikrofluidischer chip zum ausführen des verfahrens |
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US5716852A (en) * | 1996-03-29 | 1998-02-10 | University Of Washington | Microfabricated diffusion-based chemical sensor |
SE9902474D0 (sv) * | 1999-06-30 | 1999-06-30 | Amersham Pharm Biotech Ab | Polymer valves |
US6935617B2 (en) * | 2002-07-26 | 2005-08-30 | Applera Corporation | Valve assembly for microfluidic devices, and method for opening and closing the same |
DE10302720A1 (de) * | 2003-01-23 | 2004-08-05 | Steag Microparts Gmbh | Mikrofluidischer Schalter zum Anhalten des Flüssigkeitsstroms während eines Zeitintervalls |
WO2006061026A2 (en) * | 2004-12-09 | 2006-06-15 | Inverness Medical Switzerland Gmbh | A micro fluidic device and methods for producing a micro fluidic device |
US20090111197A1 (en) * | 2005-03-29 | 2009-04-30 | Inverness Medical Switzerland Gmbh | Hybrid device |
US7918244B2 (en) * | 2005-05-02 | 2011-04-05 | Massachusetts Institute Of Technology | Microfluidic bubble logic devices |
KR101097357B1 (ko) * | 2009-07-09 | 2011-12-23 | 한국과학기술원 | 다기능 미세유체 유동 제어 장치 및 다기능 미세유체 유동 제어 방법 |
DE102009048378B3 (de) | 2009-10-06 | 2011-02-17 | INSTITUT FüR MIKROTECHNIK MAINZ GMBH | Mikrofluidische Struktur |
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US20140017806A1 (en) * | 2012-07-11 | 2014-01-16 | Samsung Electronics Co., Ltd. | Microfluidic structure, microfluidic device having the same and method of controlling the microfluidic device |
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