+

WO2007071374A1 - Dispositif et procede de transport et de formation de compartiments - Google Patents

Dispositif et procede de transport et de formation de compartiments Download PDF

Info

Publication number
WO2007071374A1
WO2007071374A1 PCT/EP2006/012247 EP2006012247W WO2007071374A1 WO 2007071374 A1 WO2007071374 A1 WO 2007071374A1 EP 2006012247 W EP2006012247 W EP 2006012247W WO 2007071374 A1 WO2007071374 A1 WO 2007071374A1
Authority
WO
WIPO (PCT)
Prior art keywords
channel
transport
liquid
pump
compartment
Prior art date
Application number
PCT/EP2006/012247
Other languages
German (de)
English (en)
Inventor
Dieter Beckmann
Thomas Nacke
Gunter Gastrock
Josef Metze
Original Assignee
Institut für Bioprozess- und Analysenmesstechnik e.V.
Priority date (The priority date 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 date listed.)
Filing date
Publication date
Application filed by Institut für Bioprozess- und Analysenmesstechnik e.V. filed Critical Institut für Bioprozess- und Analysenmesstechnik e.V.
Publication of WO2007071374A1 publication Critical patent/WO2007071374A1/fr

Links

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
    • B01L3/50273—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
    • 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
    • B01L2200/0647—Handling flowable solids, e.g. microscopic beads, cells, particles
    • 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
    • B01L2200/0647—Handling flowable solids, e.g. microscopic beads, cells, particles
    • B01L2200/0668—Trapping microscopic beads
    • 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
    • B01L2200/00—Solutions for specific problems relating to chemical or physical laboratory apparatus
    • B01L2200/14—Process control and prevention of errors
    • B01L2200/143—Quality control, feedback systems
    • B01L2200/146—Employing pressure sensors
    • 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
    • B01L2300/06—Auxiliary integrated devices, integrated components
    • B01L2300/0627—Sensor or part of a sensor is integrated
    • B01L2300/0645—Electrodes
    • 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
    • B01L2300/06—Auxiliary integrated devices, integrated components
    • B01L2300/0681—Filter
    • 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
    • B01L2300/0809—Geometry, shape and general structure rectangular shaped
    • B01L2300/0816—Cards, e.g. flat sample carriers usually with flow in two horizontal directions
    • 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
    • B01L2300/0861—Configuration of multiple channels and/or chambers in a single devices
    • B01L2300/0864—Configuration of multiple channels and/or chambers in a single devices comprising only one inlet and multiple receiving wells, e.g. for separation, splitting
    • 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
    • B01L2300/0861—Configuration of multiple channels and/or chambers in a single devices
    • B01L2300/0867—Multiple inlets and one sample wells, e.g. mixing, dilution
    • 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
    • B01L2400/0475—Moving fluids with specific forces or mechanical means specific mechanical means and fluid pressure
    • B01L2400/0481—Moving fluids with specific forces or mechanical means specific mechanical means and fluid pressure squeezing of channels or chambers
    • 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
    • B01L2400/0475—Moving fluids with specific forces or mechanical means specific mechanical means and fluid pressure
    • B01L2400/0487—Moving fluids with specific forces or mechanical means specific mechanical means and fluid pressure fluid pressure, pneumatics

Definitions

  • the invention relates to a device for transporting compartments according to the preamble of claim 1 and a method for forming and transporting compartments according to the preamble of claim 26.
  • Reactor, cultivation and sorting systems for isolated microorganisms, cells, DNA and RNA are known.
  • those systems have also been described in which the separated organic material is mixed with a liquid, e.g. is surrounded by nutrient solution in the form of a microsphere.
  • the compartment consisting of organic material and surrounding nutrient solution is moved by means of a transport fluid through a channel system. Since the nutrient solution is immiscible with the transport liquid used in these transport systems, a kind of microcapsule or compartment for the enclosed organic material is produced due to the surface tension. In this way, a 3-phase system of organic material, nutrient solution and transport liquid is formed.
  • the microsphere can also be gaseous.
  • the compartments are transported by externally connected pumps for the transport fluid or the nutrient fluids and other additives.
  • These pumps are, for example, designed as syringe pumps, in which pistons are driven by a spindle. Essentially, a force or pressure is applied. Elasticities in the hose connections require a jerky, difficult to control flow.
  • the compartmentalization is also dependent on the dynamic back pressure of the fluidic system.
  • controllable pumps to the extent that they can be integrated directly into the channel structure. They are designed, for example, as diaphragm pumps and can be controlled by the pressure drop via a measuring channel.
  • Such a system is described in US 6,458,325 for a device for the automatic and continuous analysis of liquid samples. The pumps are controlled by measuring the pressure drop.
  • the micropumps of the type described would destroy the compartments.
  • dielectrophoretic drives are used in which the interaction of the cells with an electric field, which acts for example via a comb structure is exploited.
  • EP 0871 888 for example, an automated molecular biology diagnostic system with electrophoretic transport system is shown. Specifically for the transport of compartments, according to the defined 3-phase system, methods were developed according to the principle of electrowetting (US 2004/0058450), in which the droplets (compartments) are transported. Using electrophoretic drives or the principle of electrowetting, it is also possible to set up surface-trained drives with properties of sorting and singling (US 2003/0173223).
  • the compartments attach themselves to the electrodes with displacement of the transport liquid, whereby the protective shell, formed from the surface tension between transport and nutrient fluid is destroyed. There is thus the danger of infections in the form of a mutual influence on the contents of the individual compartments.
  • Another disadvantage is the risk of sedimentation of substances in large-volume chambers.
  • the known transport systems therefore have a number of disadvantages for the directional transport of compartments.
  • the sensitivity or controllability of the pumps is not given and the vibration drives of the pumps can thus lead to the destruction of the compartment.
  • the operation is not reproducible.
  • the drive attacks the organic material in the compartment against the resistance of the carrier liquid. Applied electric fields cause the formation of dipoles.
  • Another problem in particular electrical transport methods is the direct contact of the electrode surfaces.
  • the invention is therefore based on the problem to provide a device and a method for the formation and transport of compartments, in which the compartments are gently and precisely moved by the flow of the transport liquid and still takes place a feedback on the position of the compartment. Also, contact with the channel wall as well as strong electrical fields acting on the compartments should be largely avoided.
  • the device according to the invention enables control of the compartment formation and the compartment transport.
  • the control is carried out by a continuous measurement of the pressure at the respective pressure measuring devices, which control the pumps and thus regulate the pump powers in response to the change in pressure conditions in the channels.
  • Such a control allows a gentle transport of the compartments formed in the transport liquid and allows parallel tracking of the position of the compartment in the channels.
  • a first pump is associated with the transport channel and is located in the flow direction of the transport liquid in front of the mouth of the inlet channel in the transport channel, wherein the mouth of the inlet channel is formed as a nozzle.
  • At least one mechanical filter for smoothing the pulse-like pressure surges is assigned to the transport channel in the flow direction of the transport liquid between the pump and the mouth.
  • the smoothing of the pressure surges avoids negative effects on the compartments.
  • the mechanical filter is designed in the form of a chamber which is closed by an elastic membrane.
  • the natural frequency of the diaphragm is matched to the frequency of the pump.
  • the filters preferably have a cutoff frequency smaller than the pump frequency.
  • the filter characteristic can be further improved.
  • the potential effect of an unfiltered pumping frequency on the compartments can also be deliberately used, for example, to deliberately stimulate certain vital functions.
  • micro diaphragm pump As pumps bi-directional micro diaphragm pump are preferably used, which act in one direction or the other depending on the control.
  • the micromembrane pumps can be used, which act in one direction or the other depending on the control.
  • Micro channels with the diameter of about 100 microns are sufficient. This results, for example, in the diameter of compartments between 10 ⁇ m to 50 ⁇ m.
  • a piezoresistive resistor array is preferably used as a pressure measuring device.
  • the resulting measurement errors are less than 100 Pa, a value that is completely sufficient for determining passages of compartments due to possible bottlenecks.
  • An important aspect for the functioning is the time constants of the individual functional elements.
  • the transport liquid has a higher specific gravity than the liquid in the inlet channel.
  • the transport liquid is a non-polar, water-immiscible liquid, in particular C 8 to C 2 o - kettige hydrocarbons and / or or fluorinated hydrocarbons.
  • the liquid present in the feed channel is preferably an aqueous solution, in particular a buffer solution and / or a nutrient solution, and contains organic material, in particular whole cells, DNA, RNA, peptides and / or further additives such as optical active substances for the optical detection of states of the Nutrient medium (eg pH, p ⁇ 2 ) or states of the organic material (eg fluorescent substances).
  • aqueous solution in particular a buffer solution and / or a nutrient solution
  • organic material in particular whole cells, DNA, RNA, peptides and / or further additives
  • optical active substances for the optical detection of states of the Nutrient medium (eg pH, p ⁇ 2 ) or states of the organic material (eg fluorescent substances).
  • the compartments have at least one organic material encapsulated in the liquid, the diameter of the compartments formed preferably being 50 to 1000 ⁇ m, in particular 100 to 500 ⁇ m.
  • the device is further characterized in that the inlet channel opens at an angle of 10 to 170 °, in particular 70 to 120 °, in particular 90 ° in the transport channel.
  • the diameter of transport channel and inlet channel is 50 to 1000 .mu.m, in particular 100 to 700 microns; preferably 500 microns.
  • the transport channel in the flow direction of the transport liquid behind the mouth of inlet channel has a channel constriction in the transport channel downstream and / or before the channel constriction at least one pressure measuring device for controlling the first and / or another pump is arranged.
  • the channel constriction allows the determination of the distance of the compartments in the transport channel.
  • the constriction causes, when passing the compartment at a first pressure measuring device, which is arranged in the flow direction of the transport liquid before the channel constriction, a pressure increase is measured, while arranged at the flow direction of the transport liquid behind the channel constriction pressure measuring device, a reduction of the channel pressure compared to the before Passage of the channel narrowing measured pressure is determined.
  • the difference between the two pressures is also a measure of the flow rate of the transport liquid with the compartments to be transported.
  • Transport and inlet channels are part of a branched channel system.
  • the channel system is characterized in that, in the direction of flow of the transport liquid, the transport channel has a branching into at least one first outlet channel and at least one second outlet channel.
  • the branch is arranged in the flow direction of the transport liquid behind the channel constriction.
  • the branch has the function of a switch.
  • the switch function is made possible in that advantageously at least one pump for steering the compartments is assigned to at least one further channel which opens into the transport channel at the branch.
  • the channel system has at least one outflow channel, which opens in the flow direction of the transport liquid behind the branch into at least one intake channel to form a transition.
  • at least one suction pump and at least one suction chamber are associated with a pressure measuring device the intake passage.
  • the intake duct has a smaller diameter than the outflow duct at the transition.
  • the compartment Due to the narrowing of the channel thus formed, the compartment is retained at the transition due to the suction pressure, whereby measurements of various parameters such as impedance or volume can be performed.
  • at least two electrodes connected to a generator are advantageously arranged at the transition.
  • At least one titration pump is associated with at least one channel which opens into the discharge channel at the transition.
  • the entire channel system is conveniently housed in a sandwich-like arrangement.
  • the object of the invention is also achieved by a method having the features of claim 26.
  • the method for forming and transporting the compartments using the device according to the invention is characterized in that the transport liquid is transported in the transport channel by the pump in the direction of the mouth of the inlet channel, wherein by the promotion of the transport liquid, a negative pressure in the inlet channel is generated. Characterized the liquid is entrained with the organic material from the inlet channel through the mouth of the transport liquid in the transport channel to form a compartment. In this way, a three-phase system of organic
  • the method is advantageously carried out in such a way that the pressure measuring device assigned to the inlet channel measures the pressure in the inlet channel dependent on the flow rate of the transport liquid and controls the pump assigned to the transport channel in front of the mouth of the inlet channel in the transport channel for regulating the flow rate of the transport liquid in the transport channel.
  • the pumping activity is regulated by a control loop consisting of a pressure measuring device, a regulator with known transmission characteristics and a pump. It is therefore possible by the pumping regulation to control the volume of the compartments formed by the performance of the pump so that with a certain probability, depending on the intended application, exactly one part of an organic material, e.g. a single cell of a microorganism. Also, by regulating the flow rate of the transport liquid, the volume of the compartments can be adjusted as needed.
  • a pressure measuring device arranged in the flow direction of the transport liquid upstream of the channel constriction corresponds to the volume of the compartments measures dependent pressure in the transport channel and controls at least one of the steering pumps, which causes a steering of the compartments in dependence on its volume in at least one discharge channel by delivering pressure pulses.
  • a pressure measuring device arranged in the flow direction of the transport liquid upstream of the channel constriction measures the pressure in the transport channel dependent on the volume of the compartments and controls an intake pump assigned to the intake channel.
  • the suction of the suction pump causes the transport of a compartment with a specific volume in at least one of the drainage channels to the narrowing transition of the drainage channel in the intake passage.
  • the compartment is deposited and caused by the deposition of a pressure increase in the intake passage and in the suction chamber.
  • the increase in pressure in the suction chamber associated with the intake passage is measured by a pressure measuring device also associated with the intake manifold, which in turn regulates the suction of the suction pump.
  • a defined amount of an additive is transported through the boundary layer of the deposited compartment by means of a titration pump, which is assigned to another channel opening into the discharge channel at the transition.
  • Preferred additives are optical active substances for the optical detection of conditions of the nutrient medium (eg pH, pO 2 ) or states of the organic material (eg fluorescent substances).
  • the modified compartment is transported by the suction pump counter to the flow direction of the transport liquid out of the discharge channel into at least one further discharge channel.
  • the measurement of the electrical resistance or the impedance of the compartment deposited at the junction is advantageously measured at different frequencies by application of an alternating voltage generated by a generator at different frequencies over at least two electrodes in the context of electroimpedance spectroscopy.
  • Figure 1 a schematic representation of a compartment
  • Figure 2 is a schematic representation of a first embodiment of a device according to the invention.
  • Figure 3a a schematic representation of a first variant of a second
  • FIG. 3b shows a schematic representation of a second variant of a second embodiment of the device according to the invention.
  • Figure 4 is a schematic representation of a third embodiment of the device according to the invention.
  • Figure 5 is a schematic representation of a fourth embodiment of the device according to the invention.
  • Figure 6 is a schematic representation of a fifth embodiment of the device according to the invention.
  • Figure 7 is a schematic representation of a sixth embodiment of the device according to the invention.
  • Figure 8 a side view of the sixth embodiment.
  • Figure 1 illustrates schematically the structure of the compartments 5 of organic material 1, a surrounding liquid 2 e.g. Nutrient liquid, and an emerging boundary layer 7 to the non-polar transport liquid 3.
  • the compartment 5 is defined here by the boundary layer 7 between the liquid 2 in the compartment 5 and the surrounding transport liquid.
  • an additive 6 e.g. contains an agent which changes the development conditions of the organic material 1.
  • a polar liquid 2 is used in the compartment 5, it is also possible in principle, a compartment 5 with a nonpolar To move liquid (eg with an organic phase) in a polar transport liquid 3. In principle, it is also possible to use a gas as the fluid.
  • FIG. 1 A first embodiment with a generation of a compartment 5 is shown in FIG.
  • the transport liquid 3 is conveyed by a pump 20, e.g. is designed as a micromembrane pump, promoted.
  • the liquid 2 is e.g. in the form of a nutrient solution with the organic material 1; e.g. Cells of microorganisms.
  • the organic material 1 e.g. Cells of microorganisms.
  • the nutrient solution 2 in relation to the number of cells, the distance between the cells in the liquid 2 is relatively high.
  • the nutrient solution 2 is aqueous and insoluble in the transport liquid 3; it forms a boundary layer 7.
  • Compartments 5 are formed, the volume of which depends on the geometry of the nozzle 13, on the physical properties of the liquids 2 and 3, but also on the resulting negative pressure in the inlet channel 11 or on the power of the pump 20. It is now possible to control the volume of the compartment 5 by the power of the pump 20 so that with a certain probability, depending on the intended application, there is exactly one cell or one microorganism in each compartment 5.
  • the first pump 20 is here associated with the transport channel 12 for transporting the transport liquid 3.
  • the inlet channel 11 is associated with a pressure measuring device 30 for controlling the pump 20.
  • the mechanical filter 29 can be designed, for example, as a chamber which is closed by an elastic membrane and whose natural frequency is matched to the frequency of the pump 20.
  • the prevailing in the inlet channel 11 negative pressure during operation of the pump 20 builds up to a maximum, resulting in the tearing of the compartment 5 in the short term, an overpressure.
  • the pressure peak is easily measurable and can be used well as an indicator for the generation of a compartment 5.
  • the spacing of the compartment formation can be influenced with this arrangement by the fact that the pump 20 delivers, the required limit pressure in the inlet channel 1 1 for the nutrient solution 2 is not reached.
  • Figure 3a relates to a second embodiment of the device according to the invention, as with the help of a pressure measurement in the channel system and the distance between compartments 5 and the passage of compartments 5 can be measured at certain positions in the branched channel system.
  • a constriction 18 is provided in the transport channel 12, which causes a pressure increase when passing through the compartment 5 at the pressure measuring device 32, a reduction of the channel pressure compared with the pressures measured before the passage of the compartment 5 is detected at the pressure measuring device 33.
  • the difference between the two pressures is also a measure of the flow rate of the transport liquid 3 with the embedded compartments 5.
  • the pressure difference is the input signal for the setpoint / actual value comparison of the controller, which then the output signal for controlling the pump to regulate the Flow rate of the transport liquid and the distance of the compartments generated.
  • the constriction 18 preferably allows the passage of individual compartments, thus also a metrological detection of optical and / or electrical properties of the individual compartments, in particular of cells, after the passage of the channel constriction is possible.
  • the deformation of the compartment 5 and / or of the organic material 1 contained therein (cell deformation) favors the characterization due to morphological changes in particular of the cells on the one hand and the possibility of passage and thus the characterization of individual cells on the other hand. Passage of individual cells additionally allows a tomographic characterization.
  • only a single compartment 5 passes through the restriction 18, which can then be characterized by a suitable arrangement of electrodes in the area of the constriction or by optical methods.
  • the Narrowing 18 leads to a reduction in the measurement volume and thus to an increase in the spatial resolution of the characterization method.
  • the pressure increase that occurs through the constriction 18 during the passage of the compartment 5 and the organic material 1 enclosed therein may cause the compartment 5 and / or the enclosed organic material 1 to implode and be destroyed after the passage.
  • a pressure control is necessary, which acts on the pump 20 so that the conveying speed is reduced by the pump 20 to a necessary level.
  • the constriction 18 is dimensioned or designed so that only after the reduction of the conveying speed to a harmless value, the following compartment 5 reaches the constriction 18 and passes through or that the constriction is geometrically designed so that an implosion and destruction of the compartment 5 and of the organic material 1 is prevented (see specific outlet zone of the channel constriction in Figure 3b).
  • a device (third embodiment) for steering the compartments or a switch in the form of the branch 17 can also be controlled.
  • the steering pump 21 or the steering pump 22 After passage of the compartment 5 at the channel constriction 18 either the steering pump 21 or the steering pump 22 is active and gives the compartment 5 a shock that directs the compartment 5 either in the first flow channel 14 or the second flow channel 15.
  • a pulse is sufficient in this case, if at the branching point a stationary flow profile of the transport liquid 3 prevails.
  • the distance between the individual compartments 5 can also be controlled, in which, after passage of the channel constriction 18 through the second outlet channel 15, transport liquid 3 is briefly removed or metered in.
  • FIG. 5 shows a fourth embodiment of a device for
  • the suction pump 23 becomes active after passage of the compartment 5 at the constriction 18 and pulls the compartment 5 in the transition 25, which is also referred to as Titrationssitz.
  • the intake passage 19 has a substantially smaller diameter than a compartment 5, so that when touching the Transition or Titriersitzes 25 due to the surface tension of the boundary layer 7, a pressure increase is measured by the pressure measuring device 38 in the suction chamber 24, which leads to switching off the suction pump 23.
  • the compartment 5 Due to the flow in the transport channel 12 and in the discharge channel 15, the compartment 5 is held in the transition or titration seat 25. Suction pump 23 and pressure measuring device 38 can be connected to a control loop, so that the compartment 5 is pressed into the titration seat 25 with a defined force. Subsequently, the titration pump 26 is active and promotes a desired amount of additive in the compartment 5, wherein the boundary layer 7 is penetrated. After completion of the titration process, the pump 23 is active in the reverse direction, promotes transport liquid 3 through the intake ports 19 and moves the compartment 5 b to the branch point in the channel. The compartment 5 then leaves the drainage channel 14.
  • an impedance measurement of the compartment 5 are made
  • the impedance provides important information about the life functions of the organic material 1, in particular of cells.
  • the transition or titration seat 25 is equipped with at least two electrodes 40. After the compartment 5 to be measured has been drawn into the titration seat 25 by the suction pump 23, an alternating voltage of different frequency is fed to the generator 43 via the electrodes 40 and the impedance is measured at different frequencies. The measurement result is evaluated via an electronic matching amplifier stage 41 and in the evaluation system 42.
  • the device according to the invention may be sandwiched according to a sixth embodiment shown in FIGS. 7 and 8.
  • FIG. 7 shows a plan view of an arrangement of a pumping chamber 82 for the pump 20, a damping chamber 84 for the mechanical filter 29, a pressure measuring chamber 64 with pressure sensor 65 of the pressure measuring device 30, transport channel 12, inlet channel 11 and mouth 13.
  • the sandwiched arrangement is seen from the side.
  • the entire assembly is conveniently housed in a sandwich 90, in which two channel bodies 87 and 89, for example, made of silicon with semicircular channels fit each other accurately so that the circular channels are 11 and 12, for example.
  • the channel bodies 89 simultaneously contain the membranes 91, 92 and 93 for the micropumps, filters and pressure sensors by inserting the corresponding chambers 82, 84 and 64 into the channel body 89 so deeply that only a thin membrane remains.
  • Externally mounted on the channel body 89 are the actual pump drive 66 of the pump 20 in the form of a piezo disc, which forms a bimorph together with the membrane 91.
  • the transport channel 12 represents a dynamic flow resistance, which causes a directed flow depending on the shape of the drive signal.
  • the subsequent damping chamber 84 is elastically closed by the membrane 92 and filters out pressure peaks in the manner of a low-pass filter.
  • the pressure measuring device 30 is similar to the micropump 20 from a chamber which is closed with a membrane 64 and a piezoelectric layer 65 applied thereto.
  • a pressure measurement functional elements can be combined into an overall system, for example, a device for Kompartimenter Wegung with an impedimetric measuring station, a titration station, a tube memory for securing development conditions with a selection station, consisting of a further measuring station and a Soft combined.

Landscapes

  • Chemical & Material Sciences (AREA)
  • Health & Medical Sciences (AREA)
  • Dispersion Chemistry (AREA)
  • Analytical Chemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Hematology (AREA)
  • Clinical Laboratory Science (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Infusion, Injection, And Reservoir Apparatuses (AREA)
  • Apparatus Associated With Microorganisms And Enzymes (AREA)

Abstract

L'invention concerne un dispositif de transport d'au moins un compartiment (5) dans un liquide de transport (3) situé dans au moins un canal de transport (12). Au moins un canal d'amenée (11) qui présente un liquide (2) différent du liquide de transport débouche dans le canal de transport (11). Le dispositif est caractérisé par au moins une première pompe (20) associée au canal de transport (12) et qui assure le transport du liquide de transport (3) et par au moins un dispositif (30, 32, 33) de mesure de pression associé au canal de transport (12) et/ou au canal d'amenée (11) pour commander la pompe (20). L'invention concerne par ailleurs un procédé de formation et de transport d'au moins un compartiment (5).
PCT/EP2006/012247 2005-12-19 2006-12-12 Dispositif et procede de transport et de formation de compartiments WO2007071374A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
DE200510061629 DE102005061629B4 (de) 2005-12-19 2005-12-19 Vorrichtung und Verfahren zum Transport und zur Bildung von Kompartimenten
DE102005061629.1 2005-12-19

Publications (1)

Publication Number Publication Date
WO2007071374A1 true WO2007071374A1 (fr) 2007-06-28

Family

ID=37887976

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/EP2006/012247 WO2007071374A1 (fr) 2005-12-19 2006-12-12 Dispositif et procede de transport et de formation de compartiments

Country Status (2)

Country Link
DE (1) DE102005061629B4 (fr)
WO (1) WO2007071374A1 (fr)

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE102021116887A1 (de) 2021-06-30 2023-01-05 Institut für Bioprozess- und Analysenmesstechnik e.V. Anordnung zum Generieren von Fluidsequenzen in einem Multifluidtransportkanal zum Konditionieren und Detektieren der in dem Multifluidtransportkanal generierten Fluidsequenzen

Families Citing this family (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE102008039117B3 (de) * 2008-08-21 2010-05-20 Institut für Bioprozess- und Analysenmesstechnik e.V. Anordnung und Verfahren zum Erzeugen, Manipulieren und Analysieren von Kompartimenten
DE102009025007A1 (de) * 2009-06-11 2011-01-05 Technische Universität Ilmenau Vorrichtung und Verfahren zur Überführung von Fluidproben in regelmäßige Probensequenzen, sowie Verfahren zur Manipulation letzterer
DE102013217959A1 (de) 2013-09-09 2015-03-12 Efficient Robotics Gmbh Mikrofluidikanalyse-Bauelement und Herstellungsverfahren

Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2002007884A2 (fr) * 2000-07-24 2002-01-31 The Regents Of The University Of Michigan Compositions et methodes de dosage de liquides dans des microcanaux
WO2002023163A1 (fr) * 2000-09-15 2002-03-21 California Institute Of Technology Dispositifs a debit transversal microfabriques et procedes associes
US20030209059A1 (en) * 2002-03-29 2003-11-13 Aisin Seiki Kabushiki Kaisha Apparatus for sorting cells and cell alignment substrate of the same

Family Cites Families (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6949176B2 (en) * 2001-02-28 2005-09-27 Lightwave Microsystems Corporation Microfluidic control using dielectric pumping
US7901939B2 (en) * 2002-05-09 2011-03-08 University Of Chicago Method for performing crystallization and reactions in pressure-driven fluid plugs

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2002007884A2 (fr) * 2000-07-24 2002-01-31 The Regents Of The University Of Michigan Compositions et methodes de dosage de liquides dans des microcanaux
WO2002023163A1 (fr) * 2000-09-15 2002-03-21 California Institute Of Technology Dispositifs a debit transversal microfabriques et procedes associes
US20030209059A1 (en) * 2002-03-29 2003-11-13 Aisin Seiki Kabushiki Kaisha Apparatus for sorting cells and cell alignment substrate of the same

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
VILKNER T ET AL: "MICRO TOTAL ANALYSIS SYSTEMS. RECENT DEVELOPMENTS", ANALYTICAL CHEMISTRY, AMERICAN CHEMICAL SOCIETY. COLUMBUS, US, vol. 76, no. 12, 15 June 2004 (2004-06-15), pages 3373 - 3385, XP002355410, ISSN: 0003-2700 *

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE102021116887A1 (de) 2021-06-30 2023-01-05 Institut für Bioprozess- und Analysenmesstechnik e.V. Anordnung zum Generieren von Fluidsequenzen in einem Multifluidtransportkanal zum Konditionieren und Detektieren der in dem Multifluidtransportkanal generierten Fluidsequenzen
EP4122604A2 (fr) 2021-06-30 2023-01-25 Institut für Bioprozess- und Analysenmesstechnik e.V. Dispositif et procédé de génération des séquences de fluide dans un canal de transport de fluides multiples et de conditionnement et de détection des séquences de fluide générées dans le canal de transport de fluides multiples

Also Published As

Publication number Publication date
DE102005061629A1 (de) 2007-06-21
DE102005061629B4 (de) 2010-04-22

Similar Documents

Publication Publication Date Title
DE60119513T2 (de) Vorrichtung und verfahren zum einspritzen von flüssigkeiten
DE69931787T2 (de) Vorrichtung und Verfahren zur Verabreichung von Tropfen
DE19847952C2 (de) Fluidstromschalter
EP3256839B1 (fr) Dispositif et procédé de distribution de particules orientées en utilisant un champ acoustique dans des gouttes en vol libre
EP1270073B1 (fr) Système microfluidique avec régulateur
EP0177718B1 (fr) Procédé et dispositif pour le triage de particules microscopiques
DE69630036T2 (de) Durchflusszelle für proben und deren verwendung
EP1286774B1 (fr) Dispositif et procede permettant de manipuler de petites quantites de matiere
WO2002082053A2 (fr) Procede et dispositif pour manipuler de faibles quantites de liquide et/ou des particules contenues dans ce liquide
EP1745851A1 (fr) Procede, dispositif et programme pour la classification des liquides
EP1345696B1 (fr) Procede et dispositif de manipulation de petites quantites de liquides
EP0939675B1 (fr) Pompe d'ejection micromecanique pour separer par extraction de tres faibles volumes de fluide dans un fluide d'echantillonnage en ecoulement
EP1253977B1 (fr) Procede et dispositif pour evacuer d'un microsysteme fluidique, des microparticules en suspension
DE112018000184B4 (de) Automatisierte Maschine zum Sortieren biologischer Flüssigkeiten
DE102019110748B3 (de) Einrichtung und Verfahren zum Sortieren und Trennen von in Fluiden dispergierten Mikropartikeln und/oder Zellen
WO2007071374A1 (fr) Dispositif et procede de transport et de formation de compartiments
EP1424130A2 (fr) Distributeur à canaux multiples avec calibrage automatique
EP2156890B1 (fr) Agencement et procédé de production, de manipulation et d'analyse de compartiments
EP0668500A2 (fr) Microanalysateur chimique
WO2009034187A1 (fr) Système de microdosage
DE102008016121B4 (de) Vorrichtung und Verfahren zur Messung der Viskosität
DE102019219659A1 (de) Kartusche mit einem mikrofluidischen System für die Durchführung einer Analyse einer Probe
EP2440940B1 (fr) Dispositif et procédé de formation et/ou d'agencement de successions d'un ou plusieurs échantillons de fluide dans un fluide porteur
DE10117771A1 (de) Verfahren und Vorrichtung zur Manipulation kleiner Flüssigkeitsmengen und/oder darin enthaltener Teilchen
DE10318864B3 (de) Mikrofluidische Einrichtung zur gesteuerten Einleitung eines Fluids in einen Kanal

Legal Events

Date Code Title Description
121 Ep: the epo has been informed by wipo that ep was designated in this application
DPE1 Request for preliminary examination filed after expiration of 19th month from priority date (pct application filed from 20040101)
NENP Non-entry into the national phase

Ref country code: DE

122 Ep: pct application non-entry in european phase

Ref document number: 06829735

Country of ref document: EP

Kind code of ref document: A1

点击 这是indexloc提供的php浏览器服务，不要输入任何密码和下载