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
  • B01L3/50273—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
  • 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
  • B01L3/502715—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 interfacing components, e.g. fluidic, electrical, optical or mechanical interfaces
• • 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
• • 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
• • 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
  • B01L2200/0631—Purification arrangements, e.g. solid phase extraction [SPE]
• • 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
  • B01L2200/0684—Venting, avoiding backpressure, avoid gas bubbles
• • 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
  • 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
  • B01L2300/0883—Serpentine channels
• • 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 microfluidic chip for carrying out a staining or assay in biology, medicine or metallography as well as a pumping device for such a microfluidic chip.
• EP 2 931 426 B1 discloses a cartridge for preparing a biological sample, particularly for staining a sample of tissue or a collection of cells.
• the cartridge comprises a cartridge body with a reaction chamberwhich can be closed by a substrate carrying a sample, a fluidic inlet system for providing at least one reagent fluid to the reaction chamber as well as a fluidic outlet system for receiving fluid from the reaction chamber.
• a substrate closes the reaction chamber
• the fluidic inlet system, the reaction chamber and the fluidic outlet system commonly constitute a fluidic system which is closed to the environment.
• WO 2013/ 1 1 1025 (Koninklijke Philips N.V.) relates to a flow through device for staining or analysing a biological sample.
• the device comprises a support for the biological sample and a conduit in fluid communication with the support to which at least one reagent can be delivered in such a way that a biological sample provided on the support engages or interacts with the at least one liquid reagent.
• the device further comprises at least one pumping means for the delivery of the at least one liquid reagent to the conduit.
• WO 2012/ 122379 (Colorado State University Research Foundation) describes a microfluidic cytochemical staining system which may be used for multiplex staining on a slide.
• the device comprises a planar surface having a plurality of channels linking a plurality of inlets on one side of the device to a plurality of outlets on another side of the device.
• the channels form a plurality of sealed conduits between the inlets and the outlets when the device is covered by a microscopic slide.
• microfluidic chip or cartridges known in the art have the disadvantage that they have a complicated layout with mechanical systems, such as valves, which makes their production expensive and which may fail during use of the devices. Further, microfluidic devices as known in the art have to be connected to the appropriate solutions in order to carry out a specific assay, which is a source of error and necessitates a separate stock of solutions.
• a microfluidic chip for a biological, medical or metallographic staining or assay comprises a base plate with a first main side and a second main side, a reaction chamber which is open towards said first main side, means for affixing a slide on said reaction chamber in a fluid-tight manner, at least one first channel connecting at least one input opening with the reaction chamber and at least one second channel connecting the reaction chamber to a waste or outlet opening.
• the at least one first channel comprises at least one solution in a quantity which is sufficient to carry out the staining or assay in the reaction chamber.
• the microfluidic chip can be used to carry out a specific assay or staining without the need for any external supply of solutions, thus facilitating the handling and reducing the risk of error.
• the microfluidic chip may be disposed in its entirety, thus eliminating any cleaning which greatly speeds up the throughput of assays or stainings.
• the microfluidic chip does not need any mechanical elements, production costs are low and reliability is high.
• each microfluidic chip constitutes a kind of kit comprising all solutions and vessels needed to carry out a specific assay or staining. This greatly simplifies work in a laboratory as only a sufficient number of microfluidic chips for any assay or staining has to be kept in storage instead of a multitude of solutions, vessels and equipment.
• a microfluidic chip as understood in the present application is a carrier having small channels which allow the transport and processing of small amounts of liquids in the range of a few microliters up to one millilitre.
• staining means the coloration of a sample, especially of a specimen such as cells, bacteria or microorganisms by means of staining agents which bind to compounds in the sample, especially to proteins or sugars on the surface of cells, bacteria or microorganisms.
• assay means a reaction of a sample with a reactant, such as a chemical compound or an antibody which may be detected, especially by optical measurement means.
• a metallographic staining or assay is a coloration or reaction of a sample of a metal, alloy, ceramic or polymeric material with at least one staining agent or a at least one reactant, especially an etching agent.
• the base plate preferably has a rectangular or quadratic shape. Further, the corners of the base plate are preferably rounded in order to minimize the danger of injury to a user of the microfluidic chip.
• the base plate preferably has a thickness of 0.5 to 10 mm, preferably of 1 to 5 mm, most preferably of 2 mm.
• the length of the base plate preferably is from 20 mm to 100 mm, more preferably from 40 to 80 mm.
• the width of the base plate preferably is from 20 mm to 100 mm, more preferably from 40 to 80 mm. Most preferably, the base plate is rectangular and has a width and length of 60 mm. Alternatively, however, the base plate may have any other suitable shape, such as circular, elliptical or polygonal.
• the base plate preferably is made of a polymer.
• the polymer further preferably is a thermoplastic polymer, which preferably has good resistance to organic solvents.
• the base plate is made of poly(methyl methacrylate) (PMMA), acrylonitrile butadiene styrene (ABS), polylactic acid (PLA), polycarbonate (PC), polyether sulfone (PES), polyetherether ketone (PEEK), polyethylene (PE), polyphenylene sulphide (PPS), polyvinyl chloride (PVC), polyvinylidene fluoride (PVDF) or polytetrafluoroethylene (PTFE).
• PMMA poly(methyl methacrylate)
• ABS acrylonitrile butadiene styrene
• PLA polylactic acid
• PC polycarbonate
• PES polyether sulfone
• PEEK polyetherether ketone
• PE polyethylene
• PPS polyphenylene sulphide
• PVC poly
• the two main sides of the base plate preferably are parallel to each other and are separated relative to each other by the thickness of the base plate.
• the base plate further comprises at least one edge, said at least one edge defining the circumference of the base plate.
• the reaction chamber preferably is configured as recess on the first main side of the base plate.
• the reaction chamber has a base which is recessed from the first main side, said base being circumferentially bounded by at least one wall.
• the base of the reaction chamber preferably is parallel to the first main side.
• the at least one wall preferably extends at a right angle from the base. Alternatively, however, the at least one wall is inclined at an obtuse angle from the base.
• the base of the reaction chamber is of circular shape.
• the reaction chamber may also have any other suitable shape, such as rectangular, elliptical or polygonal.
• the reaction chamber preferably has a depth of at least 0.1 mm, more preferably of at least 0.15 mm.
• the depth means the distance by which the base is recessed from the first main side.
• the reaction chamber hence defines a volume between the base and the first main side.
• the reaction chamber has a circular base with a diameter of 10 mm and a depth of 0.15 mm.
• the reaction chamber is open towards the first main side and may be closed by arranging a slide on the reaction chamber. Once a slide is arranged on the reaction chamber, the reaction chamber defines a closed volume.
• a slide is a carrier for a specimen or probe which is to be subjected to a staining or assay. Slides used in connection with the microfluidic chip according to the present invention may therefore be of different configurations and materials chosen such as to be suited for the staining or assay to be carried out as well as to the probe or specimen.
• the slide which may be affixed on the reaction chamber preferably is an object slide or specimen slide.
• the slide preferably is made of glass or of a transparent polymer material, such as e.g. polymethyl methacrylate (PMMA).
• PMMA polymethyl methacrylate
• the slide preferably has a thickness of about 1 mm.
• the slide is a microscope slide with the dimensions 48 mm by 28 mm. By using glass or a transparent polymer the slide can be transferred e.g. to a microscope in order to evaluate the staining or assay.
• the slide may be a metallographic probe embedded in a body of resin.
• the metallographic probe is prepared by grinding and polishing prior to affixing the slide onto the microfluidic chip.
• the means for affixing the slide on the reaction chamber in a fluid-tight manner preferably comprise at least one sealing element forming a fluid tight seal between the reaction chamber and the slide, especially a sealing element made of silicone, rubber or a polymer material having sealing properties and being resistant to solvents. Further, the means further comprise at least one element which allows a reversible mechanical fixation of the slide on the microfluidic chip.
• the means for affixing the slide in a fluid-tight manner are preferably configured such that the slide is affixed parallel to the first main side.
• the slide is affixed on the microfluidic chip with the specimen or probe facing the reaction chamber, such that the specimen or probe may be brought into contact with the at least one solution when said at least one solution is moved into the reaction chamber.
• the at least one input opening is preferably located on an edge of the base plate. In an alternative preferred embodiment, the at least one input opening is located on the first main side or on the second main side of the base plate.
• the at least one first channel provides a fluid communication between the at least one opening and the reaction chamber.
• the reaction chamber comprises at least one opening in the at least one circumferential wall which provides a fluid communication between the at least one first channel and the volume of the reaction chamber.
• the reaction chamber comprises at least one opening defining a fluid connection between the reaction chamber and the at least one second channel.
• the at least one input opening it is possible to pump a fluid into the at least one first channel.
• the at least one solution comprised in the at least one first channel is moved towards and into the reaction chamber.
• a solution present in the reaction chamber may be further moved into the at least one second channel and towards the waste.
• the fluid is preferably pumped into the at least one input opening by means of an external pumping device, for example as described further below.
• the waste may be located on the microfluidic chip or outside of it. In the latter case, the at least one second channel abuts in the outlet opening which may be brought into communication with a waste tank. If the waste is located on the microfluidic chip the base plate preferably comprises a waste tank.
• the outlet opening in order to suck the at least one solution through the at least one first channel and into the reaction chamber.
• the at least one inlet opening remains open in order to draw air into the at least one first channel.
• the at least one solution may be drawn from the reaction chamber into the at least one second channel and through the outlet opening.
• the at least one solution is then transferred into a waste tank.
• the at least one solution preferably is a solution containing at least one staining agent, at least one reactant, a buffer, a dilutant, a destaining agent or a binding agent, such as an antibody.
• the quantity of the at least one solution comprised in the at least one first channel is sufficient to carry out the staining or assay, i.e. in the case that the staining or assay necessitates more than one solution, the at least one first channel comprises all solutions needed for the staining or assay in sufficient quantities, such that the staining or assay may be performed without the need of any additional solutions.
• the at least one solution present in the at least one first channel is suitable to carry out one specific staining or assay.
• the reaction chamber is covered by a removable protection sheet which has to be removed prior to using of the microfluidic chip.
• the at least one input opening is also covered by a removable protection sheet or removable plug.
• the reaction chamber and/or the at least one input opening are covered by a pierceable protection sheet.
• the at least one first channel comprises all solutions needed to carry out the staining or assay in a sequential order, wherein each solution is separated from a neighbouring solution in the first channel by at least one volume of a buffer or gas.
• the microfluidic chip preferably comprises only one first channel.
• the same buffer is used to separate all solutions present in the at least one first channel, i.e. each pairing of neighbouring solutions is separated by a volume of the same buffer.
• different buffers may be used to separate different pairings of neighbouring solutions from each other.
• a combination of two or more different buffers or a combination of a buffer and water may be used to separate two neighbouring solutions.
• a gas of a single compound for example nitrogen, or a mixture of gases of different compounds, such as air, may be used to separate neighbouring solutions.
• a gas of a single compound for example nitrogen, or a mixture of gases of different compounds, such as air
• Each volume of buffer or gas used to separate two neighbouring solutions may comprise the same amount of buffer or gas.
• different amounts of buffer or gas may be used to separate each pairing of solutions.
• the at least one volume of buffer or gas is from 1 mI to 15 mI, more preferably from 2 mI to 10 mI, most preferably from 3 mI to 5 mI.
• neighbouring solutions are separated by, in sequential order, a first volume of buffer, a second volume of water and a third volume of buffer. Further preferably, neighbouring solutions are separated by, in sequential order, a first volume of air, a second volume of water and a third volume of air.
• neighbouring solutions are separated by, in sequential order, a first volume of buffer, a second volume of an acid or etchant, and a third volume of buffer.
• the first and the third volume are identical.
• the first and the second volume are not identical, e.g. the first volume is smaller or bigger than the second volume.
• the second volume is identical to the first volume and/or to the second volume.
• the second volume is not identical to the first volume and/or the second volume.
• the at least one first channel extends in the form of a spiral or of a plurality of windings from the input opening to the reaction chamber. With this configuration it is possible to maximize the length of the at least one first channel on the base plate.
• the microfluidic chip preferably comprises a plurality of first channels, each of the first channels comprising one solution, wherein the chip comprises a sufficient number of solutions comprised in the first channels in order to carry out the staining or assay.
• the microfluidic chip comprises a number of first channels which corresponds to the number of solutions needed for the assay or staining.
• Each of the first channels comprises an input opening, such that by pumping a fluid into the corresponding input opening it is possible to selectively move a specific solution comprised in one of the first channels towards the reaction chamber.
• each of the first channels is in fluid connection with the reaction chamber.
• the reaction chamber preferably comprises a corresponding number of openings.
• said plurality of first channels merge into a single first channel.
• the single first channel is in fluid connection with the reaction chamber, while all the other first channels are in fluid connection with said single first channel.
• the first channels are preferably arranged in a fan-shaped configuration.
• the at least one first channel is arranged into the first main side or the second main side, wherein a sheet covers the at least one first channel, said sheet being affixed to the base plate of the microfluidic chip in a fluid tight manner, preferably by welding.
• the at least one first channel is a recess or groove in the first or second main side.
• the sheet is used to close the at least one first channel on the first or second main side.
• the sheet preferably is made of a polymer material.
• the at least one first channel may be machined into the first main side or the second main side of the base plate, e.g. by means of a CNC-mill.
• the base plate with the at least one first channel may be produced by means of injection moulding, embossing or by a roll to roll process.
• Welding yields a reliable fluid tight sealing between the base plate and the sheet.
• any other suitable means of affixing the sheet to the base plate may be used.
• the at least one first channel is arranged on the second main side, wherein at least one connection channel connects said at least one first channel to the reaction chamber.
• the at least one first channel is located on the other main side of the base plate as the reaction chamber.
• the base plate comprises at least one connection channel providing a fluid connection between the at least one first channel.
• the base plate comprises one connection channel connecting one first channel to the reaction chamber.
• the at least one connection channel preferably is arranged on one end of the at least one first channel while the at least one input opening is arranged on the other end of the at least one first channel.
• the microfluidic chip comprises a waste chamber embedded in said microfluidic chip, said waste chamber having at least one vent opening.
• the at least one vent opening preferably comprises a semi permeable membrane or the like which allows air or gases to leave the waste chamber while liquids remain within the waste tank.
• the waste tank is provided empty, i.e. without any liquid filled in.
• the volume of the waste tank is preferably chosen such that at least all solutions and buffers comprised in the at least one first channel may be filled into the waste tank.
• said reaction chamber comprises at least one rib protruding from a base of the reaction chamber.
• the at least one rib prevents the formation of bubbles when the reaction chamber is filled with a solution.
• the height of the at least one rib is chosen such that it is smaller than the height of the reaction chamber, i.e. such that a clearance remains between the at least one rib and a slide affixed on said reaction chamber.
• the reaction chamber comprises at least three ribs.
• the ribs preferably have a width of 0.1 mm to 0.5 mm, more preferably of 0.3 mm.
• the height of the at least one rib preferably is such that a clearance of at least 50 mI remains between the at least one rib and a slide affixed on the reaction chamber.
• the height of the at least one rib is about 0.1 mm.
• the at least one rib is preferably straight and has a length to span the entire reaction chamber.
• the at least one first channel preferably is from 0.3 to 1.0 mm, more preferably from 0.4 to 0.8 mm, most preferably 0.6 mm wide with a depth of preferably from 0.1 to 0.6 mm, more preferably from 0.2 to 0.4 mm, most preferably 0.3 mm.
• the at least one first channel preferably has a rectangular cross-section.
• the at least one first channel may have a cross-section in the form of a semi-circle or semi ellipse.
• the reaction chamber has a volume of 5 to 25 mI, more preferably of 10 to 20 mI, most preferably of 12 mI when said reaction chamber is closed by a slide.
• the quantity of the at least one solution is such that the at least one solution may entirely fill the entire volume of the reaction chamber when it is closed by a slide. More preferably, the quantity of the at least one first solution is such that it is bigger than the volume of the reaction chamber, preferably twice as big. This allows to expose any probe or specimen present on the slide with enough of the at least one solution.
• the at least one first channel comprises all reagents for a gram staining.
• the microfluidic chip may hence be used for gram staining of bacteria.
• the at least one first channel comprises four solutions used to perform gram staining.
• the first solution is an aqueous solution of crystal violet and 20 - 30 wt.-% ethanol (stain)
• the second solution is an aqueous solution of iodine (trapping agent)
• the third solution is a solution of ethanol and 5 - 10 wt.-% acetone (decolourizer)
• the fourth solution is an aqueous solution of safranin or fuchsine (counter stain).
• the at least one first channel may comprise an additional wash solution of ethanol and 30 - 40 wt.-% dimethyl sulfoxide (DMSO).
• DMSO dimethyl sulfoxide
• Gram staining allows to classify bacteria into two groups depending on the presence of a thick layer of peptidoglycan on the cell wall of the bacteria, to which crystal violet adheres (gram-positive bacteria).
• crystal violet adheres gram-positive bacteria.
• the use of fuchsine or safranin stains the bacteria with only a small peptidoglycan layer (gram-negative bacteria).
• the microfluidic device comprises a tag embedded within the base plate or arranged on the first main side or on the second main side which comprises a unique identification number in order to identify and track each microfluidic chip.
• the tag may be in the form of a barcode, a QR code or a RFID tag.
• the present application further relates to a pumping device with a pump and at least one seat for a microfluidic chip as described above.
• the at least one seat is configured such that at least one outlet of the pump is connectable to at least one input opening or outlet opening of a microfluidic chip arranged in a respective seat in order to pump a fluid into said at least one input opening or to apply an under-pressure to said outlet opening by means of the pump.
• the at least one seat preferably comprises means to securely attach a microfluidic chip in a removable manner.
• said at least one seat comprises mechanical means to attach a microfluidic chip.
• the mechanical attachment means may be in the form of at least one clamping element.
• the at least one seat is configured as a recess in a housing of the pumping device having a shape which is complementary to the shape of a microfluidic device. Further preferably, the at least seat is configured such that the microfluidic chip may only be placed in the respective seat in a single orientation.
• the pumping device preferably comprises a reservoir for a fluid which is pumped by means of the pump into the at least one input opening of the microfluidic chip.
• the fluid may be a liquid, such as a buffer or water, or a gas, such as an inert gas like nitrogen, helium or the like.
• the pumping device comprises an intake which may be connected to a supply of fluid, such as a water or gas supply.
• the pumping device comprises a tank for the fluid.
• the pumping device comprises an air intake in order to pump ambient air into the at least one input opening.
• the air intake preferably comprises a filter in order to prevent entry of dust particles into the at least one pump and a microfluidic chip arranged in the seat.
• the pump may be of any suitable type. More preferably, the pump is of a type which allows continuous pumping of a fluid. Preferably, the pump may generate a fluid pressure of up to 3 bar, more preferably of up to 2 bar.
• the at least one seat is configured such that the at least one input opening of a microfluidic chip arranged in a respective seat is placed flush with the at least one outlet of the at least one pump of said respective seat.
• the at least one outlet of the pump comprises a flexible seal element which allows to establish a fluid tight and reversible connection between the at least one outlet and the at least one input opening.
• the at least one seat is configured such that an outlet opening of a microfluidic chip arranged in said a respective seat is placed flush with the at least one outlet of the at least one pump of said respective seat.
• the at least one outlet of the pump comprises a flexible seal element which allows to establish a fluid tight and reversible connection between the at least one outlet of the pump and the at least one outlet opening.
• the pumping device further comprises a controller which allows to control the operation of the pump.
• the controller preferably comprises input means, such as buttons, knobs or the like.
• the controller preferably comprises an output means, such as a screen, LCD-Display or the like.
• the controller may comprise a touch screen.
• the input and/or output means allow the interaction between an operator and the pumping device.
• the pumping device preferably comprises communication means which allow the pumping device to be connected to a network, such as a local area network (LAN) or which allow a direct connection with another device.
• the communication means may be of any suitable type, such as a USB connection, a Bluetooth® connection, a WiFi connection or the like. This allows to control and to monitor the pumping device remotely, e.g. from a work station in a laboratory.
• the at least one outlet of the pump comprises a needle which is preferably linearly movable such as to be inserted into and retracted from at least one input opening or outlet opening of a microfluidic chip arranged in said seat.
• Provision of a needle allows to establish a reliable fluid tight connection between the at least one outlet of the pump and at least on input opening or outlet opening of a microfluidic chip present in said seat.
• the needle is configured to be manually movable. More preferably, the pumping device comprises at least one actuator which allows an automated movement of the needle of the at least one outlet.
• the needle preferably has a diameter and cross-section which is such as to snuggly fit into the at least one input opening or outlet opening.
• the at least one needle may be inserted into the at least one opening when placing a microfluidic chip onto the respective seat.
• the needle is removable from the at least one outlet of the pumping device. This allows an easy replacement of the needle or the exchange with a needle having another cross-section and/or size, such as to match the shape and/or size of the at least one input opening of a specific microfluidic chip.
• the pumping device comprises multiple outlets of the pump for each of the at least one seat, each outlet being connected to the same pump by means of a conduit with a valve, wherein the pumping device comprises a controller which allows to selectively open and close each of the valves.
• This embodiment allows the use of the pumping device in connection with at least one microfluidic chip with a plurality of first channels. By opening and closing the valves it is possible to selectively pump the fluid into a specific input opening and hence to move the at least one solution present in the respective first channel towards the reaction chamber.
• the pumping device comprises a camera connected to the controller in order to allow an automated evaluation of the assay or staining.
• Fig. 1 a schematic isometric view onto a second main side of a first embodiment of a microfluidic chip according to the present invention
• Fig. 2 a schematic isometric view onto a first main side of the microfluidic chip of Fig. 1;
• Fig. 3 a second main side of a second embodiment of a microfluidic chip according to the present invention as a schematic isometric drawing;
• Fig. 4 a schematic isometric representation of a pumping device according to the present invention
• Fig. 5 a schematic view of a partial stretch of a first channel of the embodiment shown on Figs. 1 and 2.
• Figs. 1 and 2 show a schematic isometric view of a first embodiment of a microfluidic chip 1 according to the present invention.
• Fig. 1 shows a view onto a second main side 3 of a base plate 2 of the microfluidic chip 1
• Fig. 2 shows a view onto a first main side 14 of the base plate 2.
• the base plate 2 of the microfluidic chip 1 comprises a reaction chamber 10 which has a general circular shape and which is open towards the first main side 14.
• the base plate 2 further comprises means for affixing a slide 1 1 on the reaction chamber 10 in a fluid tight manner, which are configured as sealing lip 13 in the embodiment as shown.
• the reaction chamber 10 comprises three ribs 12 protruding form a base of the reaction chamber 10.
• the base plate 2 of the microfluidic chip 2 comprises a first channel 4.
• the first channel 4 comprises a plurality of windings in order to maximize its length.
• the first channel 4 connects an input opening 5, which is located on a side edge of the base plate 2 with the reaction chamber 10.
• the first channel 4 merges into a connection channel 7 which allows the passage of fluid into the reaction chamber 10.
• the first channel 4 is configured as recess or groove on the second main side 3 of the base plate 2.
• a sheet 6 is placed on the second main side 3 in a fluid tight manner, especially by welding. For reasons of visibility, the sheet 6 is shown transparent on Fig. 1.
• the first channel 4 comprises all solutions needed to carry out a specific staining or assay in a sufficient amount.
• the solutions are arranged in a sequential order within the first channel, each solution being separated from a neighbouring solution by a first volume of buffer, a second volume of water and a third volume of buffer (see Fig. 5).
• the base plate 2 comprises a waste tank 8 which is connected to the reaction chamber by means of a second channel (not shown).
• the waste tank 8 comprises a vent opening 9 allowing the escape of gas from the waste tank 8.
• a probe or tissue sample is affixed on the slide 1 1 and the slide is than affixed on the reaction chamber 10, wherein the probe or tissue sample faces the reaction chamber 10.
• the solutions present in the first channel 4 may be pushed towards and into the reaction chamber 10. Any solution present in the reaction chamber 10 gets into contact with the probe or tissue sample present on the slide 1 1.
• all solutions present in the first channel 4 may be pushed into the reaction chamber 10. Any solution present in the reaction chamber 10 will be displaced into the second channel and subsequently into the waste tank 8.
• Fig. 3 shows a second main side 3 of a second embodiment of a microfluidic chip 1 according to the present invention as a schematic isometric drawing.
• the base plate 2 comprises multiple first channels 4.1 - 4.5, each with its own input opening 5.1 - 5.5. All first channels 4.1 - 4.2 merge into one of these channels 4.1 before reaching the connection channel 7 and ultimately the reaction chamber 10.
• each of the first channels 4.1 - 4.5 comprises a single solution.
• the channels 4.1 - 4.5 comprise all solutions necessary to carry out a specific staining or assay in a sufficient quantity. It is to be noted that not all first channels 4.1 - 4.5 have to contain a solution.
• first channels 4.1 - 4.5 may remain empty. This has the advantage that only one configuration of microfluidic chip 1 has to be produced which may be filled with different numbers of solutions for different stainings or assays. By pumping a fluid into a specific input opening 5.1 - 5.5 it is possible to move the solution present in the respective first channel 4.1 - 4.5 towards the reaction chamber 10. It is to be noted that the first mains side 14 is configured identical to the one disclosed in Fig. 2 for the first embodiment.
• Fig. 4 shows a schematic isometric representation of a pumping device 15 according to the present invention.
• the pumping device 15 comprises a housing 22.
• the housing 22 comprises a seat 16 for a microfluidic chip 1 according to one of the embodiments disclosed herein.
• the seat 16 is configured as a recess into which a microfluidic chip 1 may be placed.
• the pumping device 15 further comprises a pump17 with an outlet 18.
• the outlet 18 includes a needle 19 which is linearly movable.
• the seat 16 is adapted such that an input opening 5 of the microfluidic chip 1 comes into contact with the outlet 18. The needle 19 can then be moved into the input opening 5 in order to establish a fluid- tight connection.
• the pumping device 15 includes an air intake 20.
• the pump 17 pumps air from the air intake 20 through the outlet 18 and the needle 19 into the input opening 5 of a microfluidic chip 1 placed in the seat 16.
• the pumping device 15 comprises an input-/output- means 21.
• the input-/output- means may be configured as buttons or knobs with a display or as a touch-screen display.
• Fig. 5 is a schematic view of a partial stretch of a first channel 4 of the embodiment of an inventive microfluidic chip 1 as shown on Figs. 1 and 2.
• the first channel 4 comprises a first amount of a first solution 23 as well as a second amount of a second solution 27. Both solutions 23, 27 are arranged sequentially within the first channel 4. In order to prevent a mixing of both solutions 23, 27 they are separated by a first volume of buffer 24 a second volume of water 25 and a third volume of buffer 26
• the first volume of buffer 24 and the third volume of buffer 26 may be air.
• the first volume of buffer 24 and the third volume of buffer 26 may comprise the equal amount of buffer or different amounts.

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• 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)
• Sampling And Sample Adjustment (AREA)
• Automatic Analysis And Handling Materials Therefor (AREA)

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• 2020
  • 2020-06-26 WO PCT/EP2020/068079 patent/WO2021259497A1/en unknown
  • 2020-06-26 EP EP20735333.5A patent/EP4171813A1/de active Pending

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