EP2535108A1 - Microfluidic System and method of operating the system - Google Patents
Microfluidic System and method of operating the system Download PDFInfo
- Publication number
- EP2535108A1 EP2535108A1 EP20120163529 EP12163529A EP2535108A1 EP 2535108 A1 EP2535108 A1 EP 2535108A1 EP 20120163529 EP20120163529 EP 20120163529 EP 12163529 A EP12163529 A EP 12163529A EP 2535108 A1 EP2535108 A1 EP 2535108A1
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- European Patent Office
- Prior art keywords
- drum
- chamber
- pressure
- actuator
- adapter
- 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
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Classifications
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- 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
- B01L3/50273—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 or forces applied to move the fluids
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- 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
- B01L3/502738—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 integrated valves
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- 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
- B01L2200/02—Adapting objects or devices to another
- B01L2200/025—Align devices or objects to ensure defined positions relative to each other
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- 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
- B01L2200/02—Adapting objects or devices to another
- B01L2200/026—Fluid interfacing between devices or objects, e.g. connectors, inlet details
- B01L2200/027—Fluid interfacing between devices or objects, e.g. connectors, inlet details for microfluidic devices
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- 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
- B01L2200/0621—Control of the sequence of chambers filled or emptied
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- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
- B01L2300/00—Additional constructional details
- B01L2300/08—Geometry, shape and general structure
- B01L2300/0832—Geometry, shape and general structure cylindrical, tube shaped
- B01L2300/0841—Drums
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- 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
- B01L2400/06—Valves, specific forms thereof
- B01L2400/0633—Valves, specific forms thereof with moving parts
- B01L2400/0644—Valves, specific forms thereof with moving parts rotary valves
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- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y10—TECHNICAL SUBJECTS COVERED BY FORMER USPC
- Y10T—TECHNICAL SUBJECTS COVERED BY FORMER US CLASSIFICATION
- Y10T137/00—Fluid handling
- Y10T137/0318—Processes
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- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y10—TECHNICAL SUBJECTS COVERED BY FORMER USPC
- Y10T—TECHNICAL SUBJECTS COVERED BY FORMER US CLASSIFICATION
- Y10T137/00—Fluid handling
- Y10T137/598—With repair, tapping, assembly, or disassembly means
Definitions
- biochemical processes are based in particular on the handling of liquids. Typically, this manipulation is done manually with tools such as pipettes, reaction vessels, active probe surfaces or laboratory equipment. By pipetting robots or special equipment, these processes are already partially automated.
- Microfluidic systems are sometimes referred to as so-called lab-on-a-chip systems (Westentaschenlabor or chip laboratory), which accommodate the entire functionality of a macroscopic laboratory on a plastic plastic card sized plastic substrate.
- Lab-on-a-chip systems typically consist of two major components.
- a test carrier or disposable cartridge includes structures and mechanisms for the implementation of basic fluidic operations (e.g., mixers) which may consist of passive components such as channels, reaction chamber, upstream reagents, or even active components such as valves or pumps.
- the second main component is actuation, detection and control units.
- Such a lab-on-a-chip system is for example in the document DE 10 2006 003 532 A1 described.
- This system comprises a rotor chip, which is rotatably provided with respect to a stator chip.
- the rotor chip can be coupled by means of fluidic channels with the stator chip for filling or emptying the rotor chip.
- the system defined in claim 1 and the method defined in claim 15 have the advantage over conventional solutions that the cartridge is not centrifuged in a centrifuge or another force field must be suspended in order to transfer the component between the first and second chamber.
- many parameters, such as the temperature of the component can be adjusted more easily in a stationary system.
- a more flexible processing of the component is possible because the processing is independent of the speed of the centrifuge.
- Component in this case means a liquid, a gas or a particle.
- chamber is presently preferably a line section, which is designed to be open on both sides or only one side open, or a substantially closed space meant, which has an inlet and / or outlet.
- the pressure device is designed as a pump and / or pressure accumulator, wherein the pump and / or the accumulator is preferably connected by means of a pressure connection with the cartridge or integrated into the cartridge. This will simply provide the necessary pressure to transfer the component between the first and second chambers.
- a very compact construction can be achieved by means of the integration.
- the "pressure" can be an overpressure or a negative pressure relative to the ambient pressure.
- the pressure accumulator stores the component itself under pressure and the first or second chamber supplies or stores a fluidic aid under pressure, which pressurizes the at least one component.
- the pressure accumulator is designed in particular as a gas cartridge, bladder accumulator or spring accumulator.
- the auxiliary is preferably a gas, in particular air, or water.
- the cartridge has a housing, which is closed at its one end by means of an adapter, wherein the adapter has the pressure port.
- the adapter has several functions integrated into the adapter: namely once a particular sterile closure of the housing and continue to receive the pressure port.
- the pressure port can also be arranged at the end of the housing, which is opposite to the adapter.
- the adjusting device comprises an electrically, mechanically and / or pressure-operated actuator which rotates the first drum and / or moves along the central axis. The axial movement can therefore be provided in addition to the rotational movement and preferably takes place along the longitudinal axis of a housing of the cartridge.
- the actuator has a shaft which is directly or indirectly connected to the first drum in order to rotate it. This allows the first drum to be rotated without having to rotate the other drums.
- the adjusting device comprises a first bevel, which cooperates with a second bevel of the first drum, in order from a first position in which this is in a form-locking engagement with a housing of the cartridge in the rotational direction about the central axis in a second position along the central axis to spend, in which the positive connection is canceled and the first drum rotates about the central axis due to the action of a return means or another actuator.
- a kind of "ballpoint pen mechanism" is provided.
- the actuator actuates the first slope for cooperation with the second slope. That is, the actuator operates the ballpoint pen mechanism.
- the first drum is a second and / or third drum upstream or downstream relative to the central axis, wherein the actuator actuates the second and / or third drum for rotating the first drum. That is, the actuator acts indirectly on the first drum to rotate it.
- the cartridge has a housing which is closed at its one end by means of an adapter, wherein the actuator is attached to the adapter.
- the actuator is integrated in the adapter.
- the adapter has a flexible membrane which can be actuated on its one side by means of the actuator and acts on its other side on the first, second and / or third drum. This can create a more sterile outcome.
- the actuator is preferably outside the interior of the housing.
- the second chamber of the first drum is upstream or downstream relative to the central axis and formed in the second and / or third drum.
- the mixing chamber can thus be the first drum forward and / or downstream or also provided in the first drum itself.
- the mixing chamber can preferably be optionally connected to different further chambers as required.
- a second drum which has the second chamber
- a third drum which has the third chamber.
- the second drum may also have the second chamber and the third chamber, for example.
- a plurality of second chambers are provided which can be acted upon by the pressure device with a different pressure, preferably a respective second chamber means of a respective pressure port in the adapter with the pressure device or all the second chambers by means of a single pressure port in the Adapter are connected to the pressure device, wherein more preferably a respective second chamber is connected by means of a respective valve with the single pressure port.
- the printing device drives the actuator.
- the actuator drives the actuator.
- FIG. 1 shows in a sectional view a cartridge 100 and schematically a printing device 101, which together form a system 103 according to an embodiment of the present invention.
- a printing device 101 which together form a system 103 according to an embodiment of the present invention.
- FIGS. 1 to 4E the structure of the cartridge 100 will be explained in more detail below.
- the cartridge 100 includes a housing 102 in the form of a tube.
- the housing 102 may be formed as a 5 to 100 mL, especially 50 mL, centrifuge tube, 1.5 mL or 2 mL Eppendorf tube, or alternatively as a microtiter plate (e.g., 20 ⁇ L per well).
- the longitudinal axis of the housing 102 is designated 104.
- a first drum 108, a second drum 106 and a third drum 110 are accommodated in the housing 102.
- the drums 106, 108, 110 are arranged one behind the other and with their respective central axes coaxial with the longitudinal axis 104.
- the housing 102 is formed closed at its one end 112. Between the closed end 112 and the adjacent to this third drum 110, a return means, for example in the form of a spring 114 is arranged.
- the spring 114 may be in the form of a coil spring or a polymer, in particular an elastomer.
- the other end 116 of the housing 102 is closed by means of a closure 118.
- the closure 118 may be removed to remove the drums 106, 108, 110 from the housing 102.
- the housing 102 itself can be dismantled to remove the drums 106, 108, 110 or to reach the chambers, for example the chamber 136.
- the first drum 108 connected downstream of the second drum 106 comprises a mixing chamber 124 in which the reagents from the chambers 120 are mixed with the sample from the chamber 122.
- the second drum 108 includes, for example, another chamber 126 in which the mixture 128 flows from the mixing chamber 124 through a solid phase 130.
- the solid phase 130 may be a gel column, a silica matrix, or a filter.
- the third drum 110 which is in turn connected downstream of the first drum 108, comprises a chamber 132 for receiving a waste product 134 from the chamber 126. Furthermore, the third drum 110 comprises a further chamber 136 for receiving the desired end product 138.
- the mixing chamber 124 is first to be fluidly connected to the chamber 122 to receive the sample from the chamber 122. Thereafter, the mixing chamber 124 is to be connected to the chambers 120 to receive the reagents from these. Subsequently, the reagents and the sample are to be mixed in the mixing chamber 124.
- the processes in chambers 126, 132 and 136 should also be similar.
- FIG. 2A-2G perspective view of various components of the cartridge 100 from FIG. 1 , Based on Figures 2A-2G in particular an adjusting device 300 (see Fig. 3A ) comprising the actuator 139, which enables the control of the above-mentioned processes.
- the housing 102 on its inside projections 200.
- the projections 200 are radially from the housing inner wall 202 toward the longitudinal axis 104.
- the projections 200 form between them slots 204 which extend along the longitudinal axis 104.
- the projections 200 are at their one end each formed with a slope 206.
- the ramps 206 face in a first direction 207. According to the present embodiment, they point toward the end 112 of the housing 102.
- FIG. 2B shows the end 112 of the housing 102, which is formed according to this embodiment as a removable cap.
- the end 112 has at its inner periphery a plurality of grooves 208 which extend along the longitudinal axis 104.
- FIG. 2C shows the second drum 106 with the chambers 120, 122.
- the drum 106 has on its outer wall 210 a plurality of projections 212 which extend from the outer wall 210 radially outwardly.
- the projections 212 of the drum 106 engage in the slots 204 of the housing 102.
- a rotation of the drum 106 is locked about the longitudinal axis 104.
- the drum 106 is slidable along the longitudinal axis 104 in the slots 204.
- the second drum 106 furthermore has on its outer wall 210, in particular on its end 214 facing the first drum 108, a crown-like contour 216 which comprises a multiplicity of bevels 218, 220.
- Two bevels 218, 220 each form a point of the crown-like contour 216.
- the slopes 218, 220 also point in the first direction 207.
- FIG. 2D shows a view of the second drum 106 from Figure 2C from underneath.
- the underside 222 of the second drum 106 assigned to the end 214 has a plurality of openings 224 in order to connect the chambers 120, 122 to the mixing chamber 124 of the first drum 108 in liquid, gas and / or particle form (hereinafter "conductive").
- the openings 224 may also conductively connect the chambers 120, 122 to the chamber 126 of the first drum 108.
- a respective conductive connection is determined by the position of a respective opening 224 with respect to the chambers 124, 126. This position is achieved by rotating the first drum 108 relative to the second drum 106, as will be explained in more detail later.
- FIG. 2E shows a lancing device 226, which in FIG. 1 not shown.
- Lancing device 226 includes a plate 228 having one or more spikes 230 disposed adjacent to an opening 232 in plate 228, respectively.
- the mandrels 230 serve, by means of suitable control by the actuator 139 a respective Opening 224 in the bottom 222 of the second drum 106 to pierce, whereupon in particular liquid from the corresponding chamber 120, 122 flows through the opening 232 into the chambers 124 or 126.
- Figure 2F shows the first drum 108 with the chambers 124, 126.
- an opening 236 for a conductive connection of the chamber 126 with the chambers 132, 136 of the third drum 110 is provided.
- the first drum 108 has a plurality of projections 240 on its outer wall 238.
- the protrusions 240 are configured to engage the slots 204 (as well as the protrusions 212 of the second drum 106). As long as the projections 240 are engaged with the slots 240, rotation of the first drum 108 about the longitudinal axis 104 is disabled. However, the projections 240 along with the first drum 108 are movable along the longitudinal axis 104 in the slots 204.
- the protrusions 240 have bevels 242 which are opposite to the first direction in a second direction 243 and are formed corresponding to the slopes 206 and 220. According to the present exemplary embodiment, the second direction 243 points in the direction of the closure 118.
- FIG. 2G shows the third drum 110 with the chambers 132, 136.
- the drum 110 has projections 244 which project from the outer wall 246 of the drum 110 respectively.
- the projections 244 are adapted to engage the grooves 208 of the end 112 so that the drum 110 is displaceable in the longitudinal direction 104 in the grooves 208. A rotation of the drum 110 about the longitudinal axis 104 is thus locked.
- FIG. 3A-3E show several operating conditions during operation of the cartridge 100 FIG. 1 , wherein an additional drum 302 is shown, but this is not relevant in the present case.
- the Figures 4A-4E correspond respectively with the Figures 3A-3E and illustrate the movement of the ramps 206, 218, 220, 242 relative to each other.
- FIG. 3B shows an operating state of the cartridge 100 which is more advanced than that in FIG FIG. 4B shown condition.
- the housing 102 is shown partially transparent to reveal the interior.
- FIGS. 3A and 4A show a first position in which the projections 240 of the first drum 108 engage in the slots 204 and thus a rotation of the first drum 108 is locked about the longitudinal axis 104.
- the actuator 139 now presses indirectly or directly on the second drum 106, the second drum 106 in turn pushes the bevels 242 of the first drum 108 against the action of the spring 114 by means of the bevels 220 of the contour 216, the spring 114 being compressed.
- the first drum 108 moves in the first direction 207 as indicated by the corresponding arrows in FIGS FIGS. 4A and 4B indicated. This movement is continued until the protrusions 240 disengage from the protrusions 200.
- the spring 114 moves the first drum 108 again in the second direction 243 by means of the third drum 110.
- the second drum 106 together with its bevels 220 is also moved again in the second direction 243 whereby the chamfers 242 of the first drum 108 come to rest against the chamfers 206 of the housing 102 and slide therealong into a third position, as in Figs Figures 4D and 4E shown.
- the projections 240 of the first drum 108 are again located in the slots 204 of the housing 102, so that further rotation of the first drum 108 about the longitudinal axis 104 is again locked.
- the process described above may be repeated as many times as desired to rotate the first drum 108 in a defined manner relative to the other drums 106 and 110.
- the cartridge 100 may have an outer geometry, so that these in a receptacle of a rotor of the centrifuge, in particular in a receptacle of a Ausschwingrotors or fixed angle rotor of a centrifuge, can be used.
- the cartridge 100 is moved by one in FIG. 1 schematically indicated pivot point 140 rotated at high speed.
- the pivot point 140 lies on the longitudinal axis 104, so that a corresponding centrifugal force 142 along the longitudinal axis 104 acts on each component of the cartridge 100.
- suitable control of the rotational speed various processes within the cartridge 100 can be controlled, as with the use of the actuator 139.
- the actuator 139 may be electrically, mechanically and / or pressure-operated.
- a piezoelectrically, electrostatically, semi-mechanically manually or electromagnetically operated actuator 139 is suitable.
- “Operated” here means the active principle which the actuator 139 exploits in order to generate the actuating force for actuating the second drum 106 (or, depending on the embodiment, also one of the other drums 108, 110).
- the actuator 139 may include an electromagnet that cooperates with a metal part disposed in one of the drums 106, 108, 110 that the electromagnet attracts or repels by appropriately driving it, thereby effecting the above-described adjustment of the drums 106, 108, 110 to reach each other.
- the compressive force applied to the second drum 106 by means of the actuator 139 is typically 0.5-100 N.
- a suitable, not shown, control device which controls the actuator 139, so that the drums 106, 108, 110 at the desired time to take the respective desired position to each other.
- the control device may have a timer and / or an integrated circuit.
- the system 103 may be provided without the protrusions 200, the slots 204, the slopes 206, the protrusions 212, the slopes 218, 220 and return spring 114.
- the actuator 139 has a shaft which is directly connected to the first drum 108. The actuator 139 then rotates under suitable control by means of the control device, the first drum 108 with respect to the then fixed other drums 106, 110 in order to conductively connect the various chambers, for example the chambers 120, 124 with each other.
- two or more actuators 139 can be used.
- FIG. 5 schematically shows in a sectional view a system 103 according to another embodiment of the present invention.
- the lid 118 is in the form of an adapter for holding the actuator 139 is executed.
- the actuator 139 extends through the adapter 118 and thus acts directly on the second drum 106 to these in the first direction 207, ie in Fig. 5 down, to move.
- the actuator 139 for this purpose, an actuator, in particular a rod having, which presses against the drum 106.
- the provision can be made as described above by means of the return means 114.
- the actuator 139 for example, the actuator, be firmly connected to the second drum 106.
- the drum 106 can be rapidly reciprocated along the longitudinal direction 104 by means of the actuator 139, whereby a mixing chamber for mixing components in one of the chambers 120, 122 could be provided. If the amplitude of the to-and-fro motion is chosen to be sufficiently small, this movement can occur without twisting the drums 106, 108, 110 relative to each other, i. the "ballpoint pen mechanism" is not triggered.
- the pressure device 101 has the function of applying at least one component 500, in particular a liquid, for example a reagent, with a pressure difference in order to transfer it, for example, from the chamber 120 into the chamber 124.
- the chambers 120, 124 are first arranged opposite each other (by means of rotating the first drum 108, as described above) and thereafter pressure-tightly connected to each other.
- the second drum 106 seals against the adapter 118 so that a corresponding channel in the adapter 118 carrying the pressure is pressure-tightly connected to the chamber 120.
- the pressure device 101 then applies, for example, a pressure which is above the ambient pressure to the adapter-side end 502 of the chamber 120.
- the chamber 124 is vented to the atmosphere so that the pressure drives the component into the chamber 124.
- the chamber 124 in turn with other chambers 126, 132, 136 (see FIG. 1 ) in the first drum 108 and / or in the third drum 110 to be conductively connected, wherein only the last chamber 136 is vented, so that the pressure of the component 500 or a mixture of the component 500 with other components or only a component of the component 500 by the chambers 124, 132, 136 drives.
- the pressure device 101 typically generates a pressure of 0.01-2 bar.
- the pressure device 101 may also be provided to provide the pressure difference by generating a vacuum.
- the printing device 101 is designed, for example, as a pump.
- a pump for example, it can be a hand-operated or electrically operated pump.
- the printing device 101 may be formed as a pressure accumulator.
- the pressure accumulator 101 can be designed, for example, as a spring accumulator, which initially contains the component 500 itself and, in particular, conveys the component 500 through the chamber 120 into the chamber 124 by actuation of a valve.
- the printing device 101 stores a fluidic aid under pressure. As an aid especially compressed air comes into question. Relaxing the air, this drives the component 500, in particular a liquid, from the chamber 120 into the chamber 124 or through a plurality of chambers, as described above.
- the printing device 101 is provided in particular outside the cartridge 100 and connected to the cartridge 100, in particular the adapter 118, for example by means of a pressure port 504.
- the pressure device 101 in particular in the form of a compressed gas storage, could also be integrated in the cartridge 100, in particular in one of the chambers 120, 122, 124, 126, 132, 136.
- FIG. 6 schematically shows in a sectional view a system 103 according to yet another embodiment of the present invention.
- the embodiment according to FIG. 6 differs from the according to FIG. 5 in that the actuator 139 is attached to the outside of the adapter 118, ie, the actuator 139 does not penetrate the adapter 118 in this case. Rather, the actuator 139 acts indirectly, for example by means of a flexible membrane, on the second drum 106 to operate them in the first direction 207. In particular, forms thin portion 600 of the adapter 118 from the membrane, wherein an actuator 602 of the actuator 139 elastically deforms this thin portion 600.
- FIG. 7 schematically shows in a sectional view a system 103 according to yet another embodiment of the present invention.
- the embodiment according to FIG. 7 differs from the according to FIG. 5 in that a respective chamber 120, 122 of the second drum 106 is connected to a respective pressure device 101 by means of a respective associated pressure port 504. As a result, the pressures applied to the chambers 120, 122 can be controlled individually.
- the adapter 118 has a connector (not shown), e.g. the housing 102, the second drum 106 and / or the chambers 120, 122 are contacted and sealed.
- the plug-in device may have pins (not shown), which engage in the chambers 120, 122 or other openings of the drum 106 from above and seal them pressure-tight.
- the pins can also open when mating the example, previously closed chambers 120, 122 or other openings, in particular piercing a cover.
- a channel connected to a pressure port 504 which opens into an associated chamber 120, 122, can run in a respective journal.
- FIG. 8 schematically shows in a sectional view a system 103 according to yet another embodiment of the present invention.
- the embodiment according to FIG. 8 differs from the according to FIG. 7 in that a respective chamber 120, 122 in the second drum 106 are connected by means of a valve 700 to a single pressure port 504.
- the valves 700 may be integrated into the adapter 118.
- one or more spikes 802 can be provided on the inside 800 (that is to say, facing the interior of the housing 102).
- the actuator 139 Prior to the pressure drop compensation by means of the pressure device 101, the actuator 139 first actuates the second drum 106 in the second direction 243 in order thereby to seal a cover film (not shown) which closes off a respective chamber 120, 122.
- a cover film for example, made of aluminum, to pierce.
- the drums 106, 108, 110 are appropriately rotated relative to one another, as explained above.
- the spines 802 may be provided extendable. This is then a piercing of a respective cover regardless of the operation by the actuator 139 is possible.
- the actuator 139 pressure-operated, to which the actuator 139 is pressure-conductively connected to the pressure device 101 (not shown) and thus driven by the latter.
- the adapter 118 and the second drum 106 form a chamber (not shown) with each other, which is acted upon by pressure from the pressure device 101 and thus the actuator 139 is formed.
- the actuator 139 could be provided in the form of a bellows, which is provided between the adapter 118 and the second drum 106.
- the actuator 139 may also be provided elsewhere, for example between the first drum 108 and the second or third drum 106, 110.
- the actuator 139 may also be omitted, in which case the rotation of the drums 106, 108, 110 to one another takes place manually, in particular by triggering the ballpoint pen mechanism.
- a control unit controls the interaction of the actuator 139, which determines the spatial positioning of the drums 106, 108, 110 and the printing device 101, which controls the pressure for controlling the component 500 (or more components).
- drums 106, 108, 110 and the chambers 120, 122, 124, 132, 136, respectively, can be designed so that further process steps and structures can be integrated, e.g. Sedimentation structures, mixed structures, channel or siphon structures for the forwarding and switching of liquids.
- the housing 102 and the drums 106, 108, 110 may be made of the same or different polymers.
- the one or more polymers are, in particular, thermoplastics, elastomers or thermoplastic elastomers. Examples are cycloolefin polymer (COP), cyclo-olefin copolymer (COC), Polycarbonates (PC), polyamides (PA), polyurethanes (PU), polypropylene (PP), polyethylene terephthalate (PET) or poly (methyl methacrylate) (PMMA).
- COP cycloolefin polymer
- COC cyclo-olefin copolymer
- PC polyamides
- PA polyurethanes
- PU polypropylene
- PET polyethylene terephthalate
- PMMA poly (methyl methacrylate)
- One or both drums 106, 110 may be formed integrally with the housing 102.
Abstract
Description
Die Durchführung biochemischer Prozesse basiert insbesondere auf der Handhabung von Flüssigkeiten. Typischerweise wird diese Handhabung manuell mit Hilfsmitteln wie Pipetten, Reaktionsgefäßen, aktiven Sondenoberflächen oder Laborgeräten durchgeführt. Durch Pipettierroboter oder Spezialgeräte sind diese Prozesse zum Teil bereits automatisiert.The implementation of biochemical processes is based in particular on the handling of liquids. Typically, this manipulation is done manually with tools such as pipettes, reaction vessels, active probe surfaces or laboratory equipment. By pipetting robots or special equipment, these processes are already partially automated.
Mikrofluidische Systeme werden teils auch als sogenannte Lab-on-a-Chip-Systeme (Westentaschenlabor oder Chiplabor) bezeichnet, welche die gesamte Funktionalität eines makroskopischen Labors auf einem nur plastikkartengroßen Kunststoffsubstrat unterbringen. Lab-on-a-Chip-Systeme bestehen typischerweise aus zwei Hauptkomponenten. Ein Testträger oder eine Einwegkartusche beinhaltet Strukturen und Mechanismen für die Umsetzung der fluidischen Grundoperationen (z.B. Mischer) welche aus passiven Komponenten wie Kanäle, Reaktionskammer, vorgelagerten Reagenzien oder auch aktiven Komponenten wie Ventile oder Pumpen bestehen können. Die zweite Hauptkomponente sind Aktuations-, Detektions- und Steuereinheiten. Solche Systeme ermöglichen es, biochemische Prozesse vollautomatisiert durchzuführen.Microfluidic systems are sometimes referred to as so-called lab-on-a-chip systems (Westentaschenlabor or chip laboratory), which accommodate the entire functionality of a macroscopic laboratory on a plastic plastic card sized plastic substrate. Lab-on-a-chip systems typically consist of two major components. A test carrier or disposable cartridge includes structures and mechanisms for the implementation of basic fluidic operations (e.g., mixers) which may consist of passive components such as channels, reaction chamber, upstream reagents, or even active components such as valves or pumps. The second main component is actuation, detection and control units. Such systems make it possible to carry out biochemical processes fully automatically.
Ein solches Lab-on-a-Chip-System ist beispielsweise in der Druckschrift
Das in dem Anspruch 1 definierte System sowie das in dem Anspruch 15 definierte Verfahren weisen gegenüber herkömmlichen Lösungen den Vorteil auf, dass die Kartusche nicht in einer Zentrifuge zentrifugiert oder einem sonstigen Kräftefeld ausgesetzt werden muss, um die Komponente zwischen der ersten und zweiten Kammer zu transferieren. Gegenüber der Verwendung einer Zentrifuge lassen sich bei einem stationären System viele Parameter, wie beispielsweise die Temperatur der Komponente, einfacher einstellen. Weiterhin ist eine flexiblere Prozessierung der Komponente möglich, da die Prozessierung unabhängig ist von der Drehzahl der Zentrifuge.The system defined in claim 1 and the method defined in claim 15 have the advantage over conventional solutions that the cartridge is not centrifuged in a centrifuge or another force field must be suspended in order to transfer the component between the first and second chamber. Compared to the use of a centrifuge, many parameters, such as the temperature of the component, can be adjusted more easily in a stationary system. Furthermore, a more flexible processing of the component is possible because the processing is independent of the speed of the centrifuge.
Aus den Unteransprüchen ergeben sich vorteilhafte Ausgestaltungen der Erfindung.From the dependent claims, advantageous embodiments of the invention.
"Komponente" meint vorliegend eine Flüssigkeit, ein Gas oder einen Partikel."Component" in this case means a liquid, a gas or a particle.
Mit "Kammer" ist vorliegend bevorzugt ein Leitungsabschnitt, welcher beidseitig oder lediglich einseitig offen ausgebildet ist, oder ein im Wesentlichen geschlossener Raum gemeint, welcher über einen Zu- und/oder Ablauf verfügt.By "chamber" is presently preferably a line section, which is designed to be open on both sides or only one side open, or a substantially closed space meant, which has an inlet and / or outlet.
Gemäß einer Ausgestaltung des erfindungsgemäßen Systems ist die Druckeinrichtung als Pumpe und/oder Druckspeicher ausgebildet, wobei die Pumpe und/oder der Druckspeicher bevorzugt mittels eines Druckanschlusses mit der Kartusche verbunden oder in die Kartusche integriert ist. Dadurch lässt sich einfach der notwendige Druck bereitstellen, um die Komponente zwischen der ersten und zweiten Kammer zu transferieren. Außerdem kann mittels der Integration ein sehr kompakter Aufbau erzielt werden. Bei dem "Druck" kann es sich um einen Über- oder einen Unterdruck bezogen auf den Umgebungsdruck handeln.According to one embodiment of the system according to the invention, the pressure device is designed as a pump and / or pressure accumulator, wherein the pump and / or the accumulator is preferably connected by means of a pressure connection with the cartridge or integrated into the cartridge. This will simply provide the necessary pressure to transfer the component between the first and second chambers. In addition, a very compact construction can be achieved by means of the integration. The "pressure" can be an overpressure or a negative pressure relative to the ambient pressure.
Gemäß einer Ausgestaltung des erfindungsgemäßen Systems ist vorgesehen, dass der Druckspeicher die Komponente selbst unter Druck speichert und der ersten oder zweiten Kammer zuführt oder ein fluidisches Hilfsmittel unter Druck speichert, welches die wenigstens eine Komponente unter Druck setzt. Der Druckspeicher ist insbesondere als Gaskartusche, Blasenspeicher oder Federspeicher ausgebildet. Das Hilfsmittel ist bevorzugt ein Gas, insbesondere Luft, oder Wasser.According to one embodiment of the system according to the invention it is provided that the pressure accumulator stores the component itself under pressure and the first or second chamber supplies or stores a fluidic aid under pressure, which pressurizes the at least one component. The pressure accumulator is designed in particular as a gas cartridge, bladder accumulator or spring accumulator. The auxiliary is preferably a gas, in particular air, or water.
Gemäß einer Ausgestaltung des erfindungsgemäßen Systems weist die Kartusche ein Gehäuse auf, welches an seinem einen Ende mittels eines Adapters verschlossen ist, wobei der Adapter den Druckanschluss aufweist. Dadurch werden mehrere Funktionen in den Adapter integriert: nämlich einmal ein insbesondere steriler Verschluss des Gehäuses und weiterhin die Aufnahme des Druckanschlusses. Alternativ kann der Druckanschluss auch an dem Ende des Gehäuses angeordnet sein, welches dem Adapter gegenüberliegt. Gemäß einer Ausgestaltung des erfindungsgemäßen Systems umfasst die Verstelleinrichtung einen elektrisch-, mechanisch- und/oder druckbetriebenen Aktor, welcher die erste Trommel dreht und und/oder entlang der Mittelachse bewegt. Die axiale Bewegung kann demnach zusätzlich zu der Drehbewegung vorgesehen werden und erfolgt bevorzugt entlang der Längsachse eines Gehäuses der Kartusche.According to one embodiment of the system according to the invention, the cartridge has a housing, which is closed at its one end by means of an adapter, wherein the adapter has the pressure port. As a result, several functions are integrated into the adapter: namely once a particular sterile closure of the housing and continue to receive the pressure port. Alternatively, the pressure port can also be arranged at the end of the housing, which is opposite to the adapter. According to one embodiment of the system according to the invention, the adjusting device comprises an electrically, mechanically and / or pressure-operated actuator which rotates the first drum and / or moves along the central axis. The axial movement can therefore be provided in addition to the rotational movement and preferably takes place along the longitudinal axis of a housing of the cartridge.
Gemäß einer Ausgestaltung des erfindungsgemäßen Systems weist der Aktor eine Welle auf, welche mit der ersten Trommel direkt oder indirekt verbunden ist, um diese zu drehen. Dadurch kann die erste Trommel gedreht werden, ohne die anderen Trommeln drehen zu müssen.According to one embodiment of the system according to the invention, the actuator has a shaft which is directly or indirectly connected to the first drum in order to rotate it. This allows the first drum to be rotated without having to rotate the other drums.
Gemäß einer Ausgestaltung des erfindungsgemäßen Systems umfasst die Verstelleinrichtung eine erste Schräge, welche mit einer zweiten Schräge der ersten Trommel zusammenwirkt, um diese aus einer ersten Stellung, in der diese mit einem Gehäuse der Kartusche in Drehrichtung um die Mittelachse formschlüssig in Eingriff steht, in eine zweite Stellung entlang der Mittelachse zu verbringen, in welcher der Formschluss aufgehoben ist und sich die erste Trommel um die Mittelachse auf Grund der Wirkung eines Rückstellmittels oder eines weiteren Aktors dreht. Dadurch wird eine Art "Kugelschreibermechanik" vorgesehen.According to one embodiment of the system according to the invention, the adjusting device comprises a first bevel, which cooperates with a second bevel of the first drum, in order from a first position in which this is in a form-locking engagement with a housing of the cartridge in the rotational direction about the central axis in a second position along the central axis to spend, in which the positive connection is canceled and the first drum rotates about the central axis due to the action of a return means or another actuator. As a result, a kind of "ballpoint pen mechanism" is provided.
Gemäß einer Ausgestaltung des erfindungsgemäßen Systems betätigt der Aktor die erste Schräge für das Zusammenwirken mit der zweiten Schräge. D.h., der Aktor betätigt die Kugelschreibermechanik.According to one embodiment of the system according to the invention, the actuator actuates the first slope for cooperation with the second slope. That is, the actuator operates the ballpoint pen mechanism.
Gemäß einer Ausgestaltung des erfindungsgemäßen Systems ist der ersten Trommel eine zweite und/oder dritte Trommel bezogen auf die Mittelachse vor- oder nachgelagert, wobei der Aktor die zweite und/oder dritte Trommel für das Drehen der ersten Trommel betätigt. D.h., der Aktor wirkt mittelbar auf die erste Trommel, um diese zu drehen.According to one embodiment of the system according to the invention the first drum is a second and / or third drum upstream or downstream relative to the central axis, wherein the actuator actuates the second and / or third drum for rotating the first drum. That is, the actuator acts indirectly on the first drum to rotate it.
Gemäß einer Ausgestaltung des erfindungsgemäßen Systems weist die Kartusche ein Gehäuse auf, welches an seinem einen Ende mittels eines Adapters verschlossen ist, wobei der Aktor an dem Adapter befestigt ist. Dadurch werden mehrere Funktionen in den Adapter integriert: nämlich einmal ein insbesondere steriler Verschluss des Gehäuses und weiterhin die Aufnahme des Adapters. Bevorzugt ist der Aktor in den Adapter integriert. Gemäß einer Ausgestaltung des erfindungsgemäßen Systems weist der Adapter eine flexible Membran auf, welche an ihrer einen Seite mittels des Aktors betätigbar ist und an ihrer anderen Seite auf die erste, zweite und/oder dritte Trommel wirkt. Dadurch kann ein sterilerer Abschluss geschaffen werden. Der Aktor liegt bevorzugt außerhalb des Innenraums des Gehäuses.According to one embodiment of the system according to the invention, the cartridge has a housing which is closed at its one end by means of an adapter, wherein the actuator is attached to the adapter. As a result, several functions are integrated into the adapter: namely, once a particularly sterile closure of the housing and continue to receive the adapter. Preferably, the actuator is integrated in the adapter. According to one embodiment of the system according to the invention, the adapter has a flexible membrane which can be actuated on its one side by means of the actuator and acts on its other side on the first, second and / or third drum. This can create a more sterile outcome. The actuator is preferably outside the interior of the housing.
Gemäß einer Ausgestaltung des erfindungsgemäßen Systems ist die zweite Kammer der ersten Trommel bezogen auf die Mittelachse vor- oder nachgelagert ist und in der zweiten und/oder dritten Trommel ausgebildet. Indem mehrere Trommeln mit insbesondere mehreren Kammern vorgesehen werden, welche zueinander verstellt werden, lassen sich verschiedenste Prozesse mittels des Systems automatisch ausführen.According to one embodiment of the system according to the invention, the second chamber of the first drum is upstream or downstream relative to the central axis and formed in the second and / or third drum. By providing a plurality of drums with in particular a plurality of chambers, which are adjusted to one another, a very wide variety of processes can be carried out automatically by means of the system.
Gemäß einer weiteren Ausgestaltung der erfindungsgemäßen Kartusche ist die zweite Kammer und/oder eine dritte Kammer der ersten Trommel bezogen auf die Mittelachse vor- oder nachgelagert, wobei bevorzugt die erste Kammer mittels der Verstelleinrichtung wahlweise mit der zweiten Kammer oder der dritten Kammer leitend verbindbar ist. Die Mischkammer kann also der ersten Trommel vor- und/oder nachgelagert oder auch in der ersten Trommel selbst vorgesehen sein. Außerdem kann die Mischkammer bevorzugt mit unterschiedlichen weiteren Kammern - je nach Bedarf - wahlweise verbunden werden.According to a further embodiment of the cartridge according to the invention, the second chamber and / or a third chamber of the first drum with respect to the central axis upstream or downstream, wherein preferably the first chamber by means of the adjustment either with the second chamber or the third chamber is conductively connected. The mixing chamber can thus be the first drum forward and / or downstream or also provided in the first drum itself. In addition, the mixing chamber can preferably be optionally connected to different further chambers as required.
Gemäß einer weiteren Ausgestaltung der erfindungsgemäßen Kartusche ist eine zweite Trommel, welche die zweite Kammer aufweist, und/oder eine dritte Trommel vorgesehen, welche die dritte Kammer aufweist. Genauso kann jedoch auch beispielsweise die zweite Trommel die zweite Kammer und die dritte Kammer aufweisen. Gleiches gilt für die dritte Trommel. Indem mehrere Trommeln mit insbesondere mehreren Kammern vorgesehen werden, welche zueinander verstellt werden, lassen sich verschiedenste Prozesse mittels der Kartusche automatisch ausführen.According to a further embodiment of the cartridge according to the invention, a second drum, which has the second chamber, and / or a third drum, which has the third chamber. In the same way, however, the second drum may also have the second chamber and the third chamber, for example. The same applies to the third drum. By providing a plurality of drums, in particular a plurality of chambers, which are adjusted to one another, a wide variety of processes can be carried out automatically by means of the cartridge.
Gemäß einer Ausgestaltung des erfindungsgemäßen Systems sind mehrere zweite Kammern vorgesehen, welche mittels der Druckeinrichtung mit einem voneinander unterschiedlichen Druck beaufschlagbar sind, wobei bevorzugt eine jeweilige zweite Kammer mittel eines jeweiligen Druckanschlusses in dem Adapter mit der Druckeinrichtung oder sämtliche zweite Kammern mittels eines einzigen Druckanschlusses in dem Adapter mit der Druckeinrichtung verbunden sind, wobei weiter bevorzugt eine jeweilige zweite Kammer mittels eines jeweiligen Ventil mit dem einzigen Druckanschluss verbunden ist.According to one embodiment of the system according to the invention a plurality of second chambers are provided which can be acted upon by the pressure device with a different pressure, preferably a respective second chamber means of a respective pressure port in the adapter with the pressure device or all the second chambers by means of a single pressure port in the Adapter are connected to the pressure device, wherein more preferably a respective second chamber is connected by means of a respective valve with the single pressure port.
Gemäß einer Ausgestaltung des erfindungsgemäßen Systems treibt die Druckeinrichtung den Aktor an. Dadurch wird vorteilhaft lediglich eine Energiequelle für den Aktor und die Druckeinrichtung benötigt.According to one embodiment of the system according to the invention, the printing device drives the actuator. As a result, only one energy source for the actuator and the printing device is advantageously required.
Ausführungsbeispiele der Erfindung sind in den Figuren der Zeichnung dargestellt und in der nachfolgenden Beschreibung näher erläutert.Embodiments of the invention are illustrated in the figures of the drawing and explained in more detail in the following description.
Es zeigen:
- Figur 1
- ein System gemäß einem Ausführungsbeispiel der vorliegenden Erfindung, wobei eine Kartusche des Systems im Schnitt und eine Druckeinrichtung schematisch dargestellt sind;
- Figuren 2A-2G
- perspektivische Ansichten verschiedener Bauteile der Kartusche aus
Figur 1 ; - Figuren 3A-3E
- verschiedene Betriebszustände der Kartusche aus
Figur 1 ; - Figuren 4A-4E
- Detailansichten einer Verstelleinrichtung entsprechend den verschiedenen Betriebszuständen aus
Figur 3A-3E ; - Figur 5
- schematisch in einer Schnittansicht ein System umfassend einen Aktor, welcher einen Adapter durchgreift, gemäß einem weiteren Ausführungsbeispiel der vorliegenden Erfindung;
- Figur 6
- schematisch in einer Schnittansicht ein System umfassend einen Aktor, welcher an einem Adapter außenseitig angeordnet ist, gemäß einem noch weiteren Ausführungsbeispiel der vorliegenden Erfindung;
- Figur 7
- schematisch in einer Schnittansicht ein System umfassend mehrere Druckanschlüsse gemäß einem noch weiteren Ausführungsbeispiel der vorliegenden Erfindung; und
- Figur 8
- schematisch in einer Schnittansicht ein System umfassend einen Druckanschluss sowie mehrere Ventile gemäß einem noch weiteren Ausführungsbeispiel der vorliegenden Erfindung.
- FIG. 1
- a system according to an embodiment of the present invention, wherein a cartridge of the system in section and a printing device are shown schematically;
- Figures 2A-2G
- perspective views of various components of the cartridge
FIG. 1 ; - Figures 3A-3E
- different operating conditions of the cartridge
FIG. 1 ; - Figures 4A-4E
- Detail views of an adjustment according to the different operating conditions
Figure 3A-3E ; - FIG. 5
- schematically in a sectional view of a system comprising an actuator which passes through an adapter, according to another embodiment of the present invention;
- FIG. 6
- schematically in a sectional view a system comprising an actuator, which is arranged on an adapter on the outside, according to a still further embodiment of the present invention;
- FIG. 7
- schematically in a sectional view a system comprising a plurality of pressure ports according to a still further embodiment of the present invention; and
- FIG. 8
- schematically in a sectional view of a system comprising a pressure port and a plurality of valves according to a still further embodiment of the present invention.
In den Figuren bezeichnen gleiche Bezugszeichen gleiche oder funktionsgleiche Elemente, soweit nichts Gegenteiliges angegeben ist.In the figures, like reference numerals designate like or functionally identical elements, unless indicated otherwise.
Die Kartusche 100 umfasst ein Gehäuse 102 in Form eines Röhrchens. Beispielsweise kann das Gehäuse 102 als ein 5 bis 100 mL, insbesondere 50 mL, Zentrifugenröhrchen, 1.5 mL oder 2 mL Eppendorfröhrchen oder alternativ als eine Mikrotiterplatte (z.B. 20 µL pro Kavität) ausgebildet sein. Die Längsachse des Gehäuses 102 ist mit 104 bezeichnet.The
In dem Gehäuse 102 sind beispielsweise eine erste Trommel 108, eine zweite Trommel 106 und eine dritte Trommel 110 aufgenommen. Die Trommeln 106, 108, 110 sind hintereinander und mit ihren jeweiligen Mittelachsen koaxial mit der Längsachse 104 angeordnet.In the
Das Gehäuse 102 ist an seinem einen Ende 112 geschlossen ausgebildet. Zwischen dem geschlossenen Ende 112 und der zu diesem benachbart angeordneten dritten Trommel 110 ist ein Rückstellmittel beispielsweise in Form einer Feder 114 angeordnet. Die Feder 114 kann in Form einer Spiralfeder oder eines Polymers, insb. eines Elastomers, ausgebildet sein. Das andere Ende 116 des Gehäuses 102 ist mittels eines Verschlusses 118 verschlossen. Bevorzugt kann der Verschluss 118 abgenommen werden, um die Trommeln 106, 108, 110 aus dem Gehäuse 102 zu entnehmen. Alternativ kann auch das Gehäuse 102 selbst zerlegbar sein, um die Trommeln 106, 108, 110 zu entnehmen oder an die Kammern, beispielsweise die Kammer 136, zu gelangen.The
Gemäß einem weiteren Ausführungsbeispiel ist die Feder 114 zwischen dem Verschluss 118 und der zweiten Trommel 106 angeordnet, sodass die Feder 114 zum Erzeugen einer Rückstellkraft gedehnt wird. Auch andere Anordnungen der Feder 114 sind denkbar. Eine jeweilige Trommel 106, 108, 110 kann eine oder mehrere Kammern aufweisen:
- So umfasst beispielsweise die
zweite Trommel 106mehrere Kammern 120 für Reagenzien sowie eine weitereKammer 122 zur Aufnahme einer Probe, beispielsweise einer Blutprobe, die von einem Patienten entnommen wurde.
- For example, the
second drum 106 includes a plurality ofreagent chambers 120 and anotherchamber 122 for receiving a sample, such as a blood sample, taken from a patient.
Die der zweiten Trommel 106 nachgeschaltete erste Trommel 108 umfasst eine Mischkammer 124, in welcher die Reagenzien aus den Kammern 120 mit der Probe aus der Kammer 122 gemischt werden. Außerdem umfasst die zweite Trommel 108 beispielsweise eine weitere Kammer 126, in welcher das Gemisch 128 aus der Mischkammer 124 durch eine feste Phase 130 strömt. Bei der festen Phase 130 kann es sich um eine Gelsäule, eine Silicamatrix oder einen Filter handeln.The
Die der ersten Trommel 108 wiederum nachgeschaltete dritte Trommel 110 umfasst eine Kammer 132 zur Aufnahme eines Abfallprodukts 134 aus der Kammer 126. Weiterhin umfasst die dritte Trommel 110 eine weitere Kammer 136 zur Aufnahme des gewünschten Endprodukts 138.The
Ziel ist es nun, verschiedene Prozesse innerhalb der Kartusche 100 mittels eines Aktors 139 zu steuern. So soll beispielsweise die Mischkammer 124 zunächst mit der Kammer 122 fluidisch verbunden werden, um die Probe aus der Kammer 122 aufzunehmen. Hiernach soll die Mischkammer 124 mit den Kammern 120 verbunden werden, um die Reagenzien aus diesen aufzunehmen. Anschließend sollen die Reagenzien und die Probe in der Mischkammer 124 gemischt werden. Ähnlich sollen auch die Prozesse in den Kammern 126, 132 und 136 werden.The aim is now to control various processes within the
Die
Wie in
Die
Der Aktor 139, die Vorsprünge 200, die Schlitze 204, die Schrägen 206, die Vorsprünge 212, die Schrägen 218, 220, die Vorsprünge 240 sowie die Schrägen 242 bilden im Zusammenspiel mit der Rückstellfeder 114 die vorstehend erwähnte Verstelleinrichtung 300 zum definierten Verdrehen der ersten Trommel 108 gegenüber den anderen Trommeln 106, 110 um die Längsachse 104.The
Die
Gibt der Aktor 139 nunmehr die zweite Trommel 106 frei, so verschiebt die Feder 114 die erste Trommel 108 mittels der dritten Trommel 110 wieder in der zweiten Richtung 243. Dadurch wird die zweite Trommel 106 samt ihrer Schrägen 220 ebenfalls wieder in die zweite Richtung 243 bewegt, wodurch die Schrägen 242 der ersten Trommel 108 gegen die Schrägen 206 des Gehäuses 102 zum Liegen kommen und entlang dieser unter Ausführung einer weiteren Drehbewegung der ersten Trommel 108 in eine dritte Stellung gleiten, wie in den
Der vorstehend beschriebene Prozess kann beliebig oft wiederholt werden, um die erste Trommel 108 definiert gegenüber den anderen Trommeln 106 und 110 zu drehen.The process described above may be repeated as many times as desired to rotate the
Anstelle des Aktors 139 könnte nach wie vor eine Zentrifuge eingesetzt werden. Dazu kann die Kartusche 100 eine äußere Geometrie aufweisen, so dass diese in eine Aufnahme eines Rotors der Zentrifuge, insbesondere in eine Aufnahme eines Ausschwingrotors oder Festwinkelrotors einer Zentrifuge, eingesetzt werden kann. Während des Zentrifugierens wird die Kartusche 100 um einen in
Weiter alternativ könnte anstelle des Rückstellmittels 114 auch ein weiterer nicht dargestellter Aktor verwendet werden.Further alternatively, instead of the return means 114, another actuator, not shown, could be used.
Grundsätzlich kann der Aktor 139 elektrisch-, mechanisch- und/oder druckbetrieben sein. Insbesondere bietet sich ein piezoelektrisch-, elektrostatisch-, semi-mechanisch-manuell oder elektromagnetischbetriebener Aktor 139 an. "betrieben" meint hier das Wirkprinzip, welches der Aktor 139 ausnutzt, um die Betätigungskraft zum Betätigen der zweiten Trommel 106 (oder je nach Ausführungsform auch eine der anderen Trommeln 108, 110) zu erzeugen. Beispielweise kann der Aktor 139 einen Elektromagneten aufweisen, welcher mit einem in einer der Trommeln 106, 108, 110 angeordneten Metallteil zusammenwirkt, das der Elektromagnet mittels geeigneter Ansteuerung desselben anzieht oder abstößt, um dadurch die die oben erläuterte Verstellung der Trommeln 106, 108, 110 zueinander zu erreichen. Die auf die zweite Trommel 106 mittels des Aktors 139 aufgebrachte Druckkraft beträgt typischerweise 0,5-100 N.In principle, the
Bevorzugt ist eine geeignete, nicht dargestellte Steuereinrichtung vorgesehen, welche den Aktor 139 ansteuert, sodass die Trommeln 106, 108, 110 zu der gewünschten Zeit die jeweils gewünschte Position zueinander einnehmen. Dazu kann die Steuereinrichtung einen Timer und/oder einen integrierten Schaltkreis aufweisen.Preferably, a suitable, not shown, control device is provided, which controls the
Gemäß einer Ausgestaltung kann das System 103 ohne die Vorsprünge 200, die Schlitze 204, die Schrägen 206, die Vorsprünge 212, die Schrägen 218, 220 und Rückstellfeder 114 vorgesehen sein. Stattdessen weist der Aktor 139 eine Welle auf, welche mit der ersten Trommel 108 direkt verbunden ist. Der Aktor 139 dreht dann unter geeigneter Ansteuerung mittels der Steuereinrichtung die erste Trommel 108 gegenüber den dann ortsfesten anderen Trommeln 106, 110, um die verschiedenen Kammern, beispielsweise die Kammern 120, 124 miteinander leitend zu verbinden. Um eine geeignete Bewegung (eine Drehbewegung um die Längsachse 104 und/oder eine Bewegung entlang der Längsachse 104 in der ersten und/oder zweiten Richtung 207, 243) der Trommeln 106, 108, 110 zueinander zu erzielen, können auch zwei oder mehr Aktoren 139 eingesetzt werden.According to one embodiment, the
Bei diesem Ausführungsbeispiel ist der Deckel 118 in Form eines Adapters zum Halten des Aktors 139 ausgeführt. Der Aktor 139 erstreckt sich durch den Adapter 118 hindurch und greift somit direkt an der zweiten Trommel 106 an, um diese in der ersten Richtung 207, also in
Alternativ ist der Aktor 139, beispielsweise das Stellglied, fest mit der zweiten Trommel 106 verbunden werden. Dadurch lässt sich die Trommel 106 mittels des Aktors 139 schnell hin und her entlang der Längsrichtung 104 bewegen, wodurch eine Mischkammer zum Mischen von Komponenten in einer der Kammern 120, 122 vorgesehen werden könnte. Wird die Amplitude der Hin- und Herbewegung ausreichend klein gewählt, kann diese Bewegung ohne ein Verdrehen der Trommeln 106, 108, 110 zueinander geschehen, d.h. die "Kugelschreibermechanik" wird nicht ausgelöst.Alternatively, the
Die Druckeinrichtung 101 hat die Funktion zumindest eine Komponente 500, insbesondere eine Flüssigkeit, beispielweise ein Reagenz, mit einer Druckdifferenz zu beaufschlagen, um diese beispielsweise aus der Kammer 120 in die Kammer 124 zu transferieren. Dazu werden die Kammern 120, 124 zunächst einander gegenüber angeordnet (mittels Drehens der ersten Trommel 108, wie oberhalb beschrieben) und hiernach miteinander druckdicht verbunden. Außerdem dichtet die zweite Trommel 106 gegenüber dem Adapter 118 ab, sodass ein entsprechender Kanal in dem Adapter 118, welcher den Druck führt, druckdicht mit der Kammer 120 verbunden ist. Die Druckeinrichtung 101 legt dann beispielweise einen Druck, welcher oberhalb des Umgebungsdrucks liegt, an das adapterseitige Ende 502 der Kammer 120 an. Die Kammer 124 ist beispielsweise zur Umgebung hin entlüftet, sodass der Druck die Komponente in die Kammer 124 treibt. Alternativ kann die Kammer 124 wiederum mit weiteren Kammern 126, 132, 136 (siehe
Alternativ kann die Druckeinrichtung 101 auch dazu vorgesehen sein, die Druckdifferenz mittels Erzeugens eines Vakuums bereitzustellen.Alternatively, the
Die Druckeinrichtung 101 ist beispielweise als Pumpe ausgebildet. Z.B. kann es sich um eine handbetriebene oder elektrisch betriebene Pumpe handeln.The
Alternativ kann die Druckeinrichtung 101 als Druckspeicher ausgebildet sein. Der Druckspeicher 101 kann beispielweise als Federspeicher ausgebildet sein, welcher anfangs die Komponente 500 selbst enthält und insbesondere durch Betätigung eines Ventils die Komponente 500 durch die Kammer 120 in die Kammer 124 fördert. Weiterhin besteht die Möglichkeit, dass die Druckeinrichtung 101 ein fluidisches Hilfsmittel unter Druck speichert. Als Hilfsmittel kommt insbesondere komprimierte Luft in Frage. Entspannt die Luft, treibt diese die Komponente 500, insbesondere eine Flüssigkeit, aus der Kammer 120 in die Kammer 124 bzw. durch eine Vielzahl von Kammern, wie oberhalb beschrieben.Alternatively, the
Die Druckeinrichtung 101 ist insbesondere außerhalb der Kartusche 100 vorgesehen und beispielweise mittels eines Druckanschlusses 504 mit der Kartusche 100, insbesondere dem Adapter 118, verbunden. Alternativ könnte die Druckeinrichtung 101, insbesondere in Form eines Druckgasspeichers, auch in die Kartusche 100, insbesondere in eine der Kammern 120, 122, 124, 126, 132, 136, integriert sein.The
Das Ausführungsbeispiel gemäß
Das Ausführungsbeispiel gemäß
In einer Ausführungsform besitzt der Adapter 118 eine Steckeinrichtung (nicht dargestellt), wodurch z.B. das Gehäuse 102, die zweite Trommel 106 und/oder die Kammern 120, 122 kontaktiert und abgedichtet werden. Der Steckeinrichtung kann Zapfen (nicht dargestellt) aufweisen, welche in die Kammern 120, 122 oder sonstige Öffnungen der Trommel 106 von oben eingreifen und diese druckdicht verschließen. Die Zapfen können auch beim Zusammenstecken die beispielweise zuvor verschlossenen Kammern 120, 122 oder sonstigen Öffnungen öffnen, insbesondere eine Abdeckfolie durchstechen. In einem jeweiligen Zapfen selbst kann wiederum ein mit einem Druckanschluss 504 verbundener Kanal verlaufen, welcher in eine zugeordnete Kammer 120, 122 mündet.In one embodiment, the
Das Ausführungsbeispiel gemäß
Außerdem ist anhand von
Alternativ können die Dornen 802 auch ausfahrbar vorgesehen sein. Damit ist dann ein Durchstoßen einer jeweiligen Abdeckfolie unabhängig von der Betätigung durch den Aktor 139 möglich.Alternatively, the
Weiterhin besteht die Möglichkeit, den Aktor 139 druckbetrieben vorzusehen, wozu der Aktor 139 druckleitend mit der Druckeinrichtung 101 verbunden (nicht dargestellt) ist und somit von dieser angetrieben wird. Im einfachsten Fall bilden der Adapter 118 und die zweite Trommel 106 eine Kammer (nicht dargestellt) miteinander, welche mit Druck von der Druckeinrichtung 101 beaufschlagt und somit der Aktor 139 gebildet wird. Weiterhin könnte der Aktor 139 in Form eines Balgs vorgesehen werden, welcher zwischen dem Adapter 118 und der zweiten Trommel 106 vorgesehen ist.Furthermore, it is possible to provide the
Der Aktor 139 kann auch an anderer Stelle vorgesehen sein, beispielsweise zwischen der ersten Trommel 108 und der zweiten oder dritten Trommel 106, 110.The
Im einfachsten Fall kann der Aktor 139 auch weggelassen werden, wobei dann das Drehen der Trommeln 106, 108, 110 zueinander manuell erfolgt, insbesondere durch Auslösen der Kugelschreibermechanik.In the simplest case, the
Eine nicht dargestellte Steuereinheit regelt das Zusammenspiel des Aktors 139, welcher die räumliche Positionierung der Trommeln 106, 108, 110 vorgibt und der Druckeinrichtung 101, welche den Druck zur Steuerung der Komponente 500 (oder mehrerer Komponenten) kontrolliert.A control unit, not shown, controls the interaction of the
Des weiteren können die Trommeln 106, 108, 110 bzw. die Kammern 120, 122, 124, 132, 136 so ausgelegt werden, dass weitere Prozessschritte und Strukturen integriert werden können z.B. Sedimentationsstrukturen, Mischstrukturen, Kanal- oder Siphonstrukturen zum Weiterleiten und Schalten der Flüssigkeiten.Furthermore, the
Das Gehäuse 102 und die Trommeln 106, 108, 110 können aus demselben oder unterschiedlichen Polymeren hergestellt sein. Bei dem einen oder mehreren Polymeren handelt es sich insbesondere um Thermoplaste, Elastomere oder thermoplastische Elastomere. Beispiele sind Cyclo-olefin Polymer (COP), Cyclo-olefin Copolymer (COC), Polycarbonate (PC), Polyamide (PA), Polyurethane (PU), Polypropylen (PP), Polyethylene terephthalate (PET) oder Poly(methyl methacrylate) (PMMA).The
Einer oder beide Trommeln 106, 110 können einstückig mit dem Gehäuse 102 gebildet sein.One or both
Obwohl die Erfindung vorliegend anhand bevorzugter Ausführungsbeispiele beschrieben wurde, ist sie darauf keineswegs beschränkt, sondern auf vielfältige Weise modifizierbar. Insbesondere sei darauf hingewiesen, dass die für das erfindungsgemäße System vorliegend beschriebenen Ausgestaltungen und Ausführungsbeispiele entsprechend auf das erfindungsgemäße Verfahren anwendbar sind, und umgekehrt. Ferner wird darauf hingewiesen, dass "ein" vorliegend keine Vielzahl ausschließt.Although the invention has been described herein with reference to preferred embodiments, it is by no means limited thereto, but modifiable in many ways. In particular, it should be pointed out that the embodiments and exemplary embodiments described herein for the system according to the invention are correspondingly applicable to the method according to the invention, and vice versa. It is further noted that "a" in the present case does not exclude a plurality.
Claims (15)
eine Kartusche (100) mit einer ersten Trommel (108), welche eine erste Kammer (124) aufweist, und mit einer Verstelleinrichtung (300), welche dazu eingerichtet ist, die erste Trommel (108) um deren Mittelachse (104) zu drehen, um dadurch die erste Kammer (124) mit einer zweiten Kammer (120, 122, 132, 136) flüssigkeits-, gas- und/oder partikelleitend zu verbinden, und
eine Druckeinrichtung (101), welche zumindest eine Komponente (500) mit einer Druckdifferenz beaufschlagt, um diese dadurch zwischen der ersten Kammer (124) und zweiten Kammer (120, 122, 132, 136) zu transferieren.Microfluidic system (103) comprising
a cartridge (100) having a first drum (108) having a first chamber (124) and an adjustment device (300) adapted to rotate the first drum (108) about the central axis (104) thereof; thereby to connect the first chamber (124) with a second chamber (120, 122, 132, 136) liquid-, gas- and / or particle-conducting, and
a pressure device (101), which acts on at least one component (500) with a pressure difference, in order thereby to transfer between the first chamber (124) and the second chamber (120, 122, 132, 136).
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
DE201110077101 DE102011077101A1 (en) | 2011-06-07 | 2011-06-07 | Microfluidic system and method of operating such a system |
Publications (2)
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EP2535108A1 true EP2535108A1 (en) | 2012-12-19 |
EP2535108B1 EP2535108B1 (en) | 2016-10-12 |
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ID=47002496
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EP12163529.6A Not-in-force EP2535108B1 (en) | 2011-06-07 | 2012-04-10 | Microfluidic System and method of operating the system |
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US (1) | US9381511B2 (en) |
EP (1) | EP2535108B1 (en) |
CN (1) | CN102814203B (en) |
DE (1) | DE102011077101A1 (en) |
Cited By (4)
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EP2532426A3 (en) * | 2011-06-07 | 2013-03-27 | Robert Bosch Gmbh | Cartridge, centrifuge and method |
EP2532427A3 (en) * | 2011-06-07 | 2013-03-27 | Robert Bosch Gmbh | Cartridge, centrifuge and method |
EP2532428A3 (en) * | 2011-06-07 | 2013-04-03 | Robert Bosch Gmbh | Cartridge, centrifuge and method for mixing a first and a second component |
WO2015049074A1 (en) * | 2013-10-02 | 2015-04-09 | Hahn-Schickard-Gesellschaft für angewandte Forschung e.V. | Device and method for moving a solid phase into a plurality of chambers |
Families Citing this family (5)
Publication number | Priority date | Publication date | Assignee | Title |
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DE102011077101A1 (en) * | 2011-06-07 | 2012-12-13 | Robert Bosch Gmbh | Microfluidic system and method of operating such a system |
DE102013222283B3 (en) | 2013-11-04 | 2015-01-15 | Robert Bosch Gmbh | Apparatus and method for handling reagents |
WO2016105508A2 (en) * | 2014-12-23 | 2016-06-30 | California Institute Of Technology | Devices and methods for autonomous measurements |
EP3338096B1 (en) * | 2015-08-24 | 2024-03-06 | Illumina, Inc. | In-line pressure accumulator and flow-control system for biological or chemical assays |
DE102018206066A1 (en) * | 2018-04-20 | 2019-10-24 | Robert Bosch Gmbh | Device for coupling a cartridge for a chip laboratory analyzer, chip laboratory analyzer and method for coupling a cartridge for a chip laboratory analyzer |
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2012
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- 2012-06-05 US US13/488,557 patent/US9381511B2/en active Active
- 2012-06-06 CN CN201210184065.7A patent/CN102814203B/en not_active Expired - Fee Related
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WO2015049074A1 (en) * | 2013-10-02 | 2015-04-09 | Hahn-Schickard-Gesellschaft für angewandte Forschung e.V. | Device and method for moving a solid phase into a plurality of chambers |
Also Published As
Publication number | Publication date |
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US20120312380A1 (en) | 2012-12-13 |
EP2535108B1 (en) | 2016-10-12 |
US9381511B2 (en) | 2016-07-05 |
DE102011077101A1 (en) | 2012-12-13 |
CN102814203B (en) | 2016-02-10 |
CN102814203A (en) | 2012-12-12 |
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