EP3199240A1 - Cellule d'ecoulement microfluidique comprenant une electrode integree et son procede de fabrication - Google Patents
Cellule d'ecoulement microfluidique comprenant une electrode integree et son procede de fabrication Download PDFInfo
- Publication number
- EP3199240A1 EP3199240A1 EP16152755.1A EP16152755A EP3199240A1 EP 3199240 A1 EP3199240 A1 EP 3199240A1 EP 16152755 A EP16152755 A EP 16152755A EP 3199240 A1 EP3199240 A1 EP 3199240A1
- Authority
- EP
- European Patent Office
- Prior art keywords
- flow cell
- electrode
- carrier body
- cell according
- cavity
- 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.)
- Pending
Links
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Images
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
- B01L3/502715—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
- 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
- B01L3/502707—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 manufacture of the container or its components
-
- 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
- B01L2200/0689—Sealing
-
- 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
- B01L2300/04—Closures and closing means
- B01L2300/041—Connecting closures to device or container
- B01L2300/042—Caps; Plugs
-
- 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
- B01L2300/04—Closures and closing means
- B01L2300/046—Function or devices integrated in the closure
-
- 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
- B01L2300/0627—Sensor or part of a sensor is integrated
- B01L2300/0663—Whole 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
- B01L2300/08—Geometry, shape and general structure
- B01L2300/0861—Configuration of multiple channels and/or chambers in a single devices
- B01L2300/0877—Flow chambers
Definitions
- the invention relates to a microfluidic flow cell with an electrode or sensor device arranged within the flow cell, from which at least one connecting conductor is led to a connection contact accessible from the outside.
- the invention further relates to a method for producing such a flow cell.
- microfluidic flow cells (labs on a chip) are increasingly used in the so-called life sciences, e.g. for the analysis of body fluids, drinking water or other environmental samples preferably immediately after sampling. For example, in the investigation of food samples or the cultivation, processing and analysis of cells microfluidic flow cells are used.
- microfluidic flow cells An essential aspect of the use of microfluidic flow cells is the cost-effective mass production as a disposable product. This has the consequence that, as far as possible, plastics and methods of plastics processing are used in the production of such flow cells.
- microfluidic flow cells for example, essentially plate-shaped plastic parts with cavities open to a plate side and the cavities injection-molded on one side open for the formation of fluid channels and / or reaction chambers are closed with a film.
- dry reagents can be introduced into cavities or channels prior to the connection of the sprayed plastic part with the film.
- a special method for introducing dry reagents into a flow cell through such reagents receiving carrier body is in WO 2015/001070 A1 described.
- Electrode pads deposited on a portion of a flow cell interfere with the connection of the member to a cover member, eg, a connection by laser welding, so that the height of the traces, which must be compensated for by the connection technique for leak-free sealing of the flow cell, is limited and inexpensive screen printing for the production of electrodes and electrical conductors therefore in many cases is not eligible.
- thin printed conductors are sensitive and always exposed to the risk of cracking, especially in the manufacturing process. With adhesive tapes there is always the danger of detachment.
- the fluid-tight installation of electrodes or sensors connected to connecting conductors in flow cells requires a high production outlay.
- the object of the invention is to reduce the manufacturing outlay required for flow cells with built-in electrodes or sensors while increasing the reliability of the flow cells.
- a flow cell according to the invention which solves this object is characterized in that the electrode or sensor device is arranged on an insulating carrier body, the connecting conductor is embedded in the carrier body and the carrier body can be inserted into an opening in the flow cell by arranging the electrode or sensor device in the flow cell.
- an electrode or sensor device including externally accessible connection conductors, is produced by a separate component which can be inserted into the flow cell.
- the electrode or sensor device contacts a fluid in a cavity within the flow cell, the opening forms a passage to the cavity, the carrier body is fluid-tight inserted into the passage and the connection conductor is fluid-tightly embedded in the carrier body. While the connection conductor can be easily embedded in the carrier body, only the carrier body inserted into the passage takes over the further sealing of the cavity.
- the carrier body is designed in the manner of a stopper with an end face receiving the electrode or sensor device and a rotationally symmetrical, in particular conical, sealing surface which preferably forms a sealing press fit with the passage to the cavity.
- the passage is preferably provided in a rigid, plate-shaped plastic injection-molded part in its basic form, wherein the plastic injection-molded part on its side facing away from the passage recesses for forming the cavity, preferably of channels and chambers comprises.
- the plastic injection-molded part on its side facing away from the passage recesses for forming the cavity, preferably of channels and chambers comprises.
- To close the cavities is a connected to the flat plate surface foil or another injection molding.
- On the end face of the carrier body can be a plurality of electrodes, e.g. by screen printing, easily apply and their connection conductor through the support body through and insulated and fluid-tight lead to the outside.
- the electrodes can be functionalized by coatings, for example as a molecule scavenger. On the other hand, by coating a passivation of conductor surfaces in the desired extent possible.
- the externally accessible terminal contact is formed directly on the carrier body and provided for contacting by an operator device for the flow cell.
- a connecting conductor penetrating the carrier body can be widened at one end.
- the carrier body is formed with an outwardly open cavity, e.g. hat-shaped or cap-shaped.
- connection contact may be formed on a bottom wall of the cavity opposite the cavity opening. Connection elements of the operator device then engage in this cavity.
- the carrier body is produced as an injection-molded plastic part. It may consist exclusively of a plastic part or be formed as a composite part, wherein in particular the cavity opposite support wall for the electrode or the sensor may be formed of a deviating from the remaining material of the support body material, e.g. made of ceramic.
- the carrier body has an area for manual handling or mechanical assembly.
- This may in particular be a flange projecting from the rotationally symmetrical sealing surface, which forms a hat brim in the case of a hat-shaped design of the carrier body.
- the carrier body inserted into the opening in the flow cell can, in particular in addition to a connection by means of an interference fit, furthermore be permanently connected to the flow cell, e.g. by welding or gluing.
- welds are formed on the carrier body at a distance from an embedded connection conductor and / or an electrode or sensor device in order to avoid impairments of these parts by the weld.
- a flow cell comprises a plate-shaped injection molding component 1, which consists for example of PMMA, PC, COC, PS, PEEK, PE or PP.
- the injection molding component 1 is connected to a sheet side with a film 2, in particular glued or welded.
- Channel structures 3, 4, 5 and 6 are formed between the injection molding component 1 and the film 2 by depressions in the injection molding component, which are in communication with input / output ports 7 on the side of the injection molding component 1 facing away from the film 2.
- the channel structures 3 to 6 are each assigned a passage 8 which opens to the channel structure and has an inlet connection 9 projecting from the injection molding component 1.
- fluid-tight plugs 10,10 ', 10 "and 10"' are used, wherein, as is Fig. 2 can be seen, the plug end face in each case reaches the channel structure 3,4,5 and 6 and limits this.
- the reference numeral 11 indicates electrical contact elements of an (not shown otherwise) operator device, which serve for contacting with the plug connected conductors, as explained below.
- Fig. 3 2 shows the plug 10 "'in two different views (a) and (b) and in a sectional view (c) .
- the plug is basically a plastic injection-molded part which, like the injection-molded part 1, preferably consists of PMMA, PC, COC, COP, PP or PE and forms a carrier part.
- the cap-shaped with a one-sided open cavity 12 formed plug 10 '" has an annular opening surrounding the opening of the cavity 13.
- One of the opening of the cavity opposite bottom wall 14 pass through electrically conductive connecting conductor pieces 15 and 15 '.
- connection conductor pieces On the inside of the plug 10 ", these connection conductor pieces each form a connection contact for a connection element 11 of the operator device.” On the outside of the plug, the conductor pieces 15, 15 'are each connected to a linear electrode 16 or 16' elongated, mutually parallel electrodes 16,16 'intersect perpendicularly in the mounting position provided for the plug 10'"the channel structure. 6
- the conductor pieces 15, 15 'penetrating the bottom wall 14 may be printed, e.g. by screen printing of metal pastes such as silver paste or solder.
- the elongated, active electrodes are preferably electrodes made of metal, in particular gold, platinum, chromium, copper or aluminum.
- the thickness or height of the electrodes is preferably between 50 nm and 1 ⁇ m. For the production of these electrodes in particular the thin-film technique or a thermal transfer printing into consideration.
- the electrodes 16, 16 'crossing the channel structure 6 are each about 50 ⁇ m wide and e.g. for cell counting (according to the principle of the Coulter Counter) suitable.
- a conical sealing surface 17 of the stopper 10 '" forms a press fit
- the slope of the sealing surface 17 corresponds to the Luer standard (6% gradient).
- the stopper 10'" is additionally connected, eg welded, beyond the interference fit with the plastic injection-molded part 1.
- Fig. 4a and 4b Plugs 10 "shown in different positions differ from the plug 10" in that a plurality of terminal conductors 18 penetrating the bottom wall 14 are arranged in a bottom wall 14 in an annular arrangement.
- the conductor pieces 18 are connected on their side facing the channel structure 5 each via an elongated conductor piece with a circular electrode 19, wherein a rectangular field of such circular electrodes 19 is formed.
- a passivation layer ensures that of the arranged on the bottom wall 14 ladder parts only the circular conductor parts can be effective as an active, interacting with the fluid electrodes 19.
- the in Fig. 5 shown plug 10 ' has a preferably injection-molded from the above plastics base body, wherein a bottom wall 14' made of ceramic, another plastic or glass separately and connected for example by pressing, gluing or welding with the plastic body.
- the bottom wall 14 ' is penetrated by conically shaped in the embodiment shown connecting conductor pieces 20, which are for example produced by screen printing.
- the conical conductor pieces 20 are connected to active electrodes 21 and 22 on the front side of the bottom wall 14 ', wherein the active electrodes consist for example of silver or silver chloride.
- the active electrodes consist for example of silver or silver chloride.
- they may be printed and made of different metals.
- the two electrodes can be, for example, a measuring electrode and a reference electrode for electrochemical investigations.
- plug 10 is not formed as the above-described plug as hollow but as a solid body in which a plurality of terminal conductor pieces 23 are embedded in an annular arrangement.
- the conductor pieces are each connected to straight, parallel electrodes 24, on the outer end of the plug open the conductor pieces 23 as widened connection contacts 25 for contacting by an operator device.
- the conductor pieces 23 are preferably formed by wires or stamped and formed sheets which are integrated into the plug 10 by overmolding during the injection molding process.
- the six parallel electrodes 24 cross the channel structure 3. In the even, active Electrodes 24 are printed electrodes in the example shown.
- the electrodes 24 are suitable for example for impedance measurements.
- a stopper 10 ', 10 ", 10"' similar to the stopper described above may be adjacent to different cavities of a flow cell, eg, according to FIG Fig. 7a to a channel 26 which is wider than the end face of the plug facing it, or according to Fig. 7c to a channel 27 which is narrower than this end face.
- the plug can be placed particularly precisely with respect to the channel 27 by the narrow channel forms support shoulders for the end face of the plug.
- the distance between the electrode and the channel bottom can be maintained very accurately.
- Fig. 7b shows a plug adjacent to a reaction chamber 28 of a flow cell.
- FIG. 8 A plug protrudes, which is provided with a positioning stop 29 for placing the plug in an intended rotational position relative to the flow cell. Accordingly, an injection molded part 1 of the flow cell has a counter element 30 for the positioning stop 29.
- Fig. 9 shows various possibilities for additional, permanent attachment of a plug inserted into a flow cell, wherein Fig. 9a the possibility of ultrasonic or thermal welding by means of a dome-shaped welding tool 31 indicates.
- Fig. 9b shows a laser weld 32 between an annular flange 13 of the plug and an inlet nozzle 9 of an injection molded component 1, wherein the inlet nozzle 9 is formed of a plastic material which absorbs the laser radiation to a particular extent at the wavelength of the laser light used for laser welding.
- Fig. 9c shows a laser weld 33 on the side of the plug, which faces the channel region of the flow cell and which is optionally to produce prior to connection of an injection molded substrate 1 with a film 2. With sufficiently transparent film 2, the welding can also be done afterwards.
- electrodes formed on one plug are combined with another electrode 35 introduced into a channel 34 at a distance from the plug.
- the electrodes can cooperate in a suitable manner, for example as opposing electrodes between which the fluid is transported in the channel of the flow cell, which opens up further opportunities for interaction.
- Fig. 10b shows a plug, the end face on a foil 2, which closes a channel structure, rests, wherein in the end face of the plug itself, a channel portion 36 is formed. Electrodes 37 and 38 connected to the plug are disposed in the channel section 36 opposite each other.
- Fig. 11 shows an embodiment of a plug, on whose channel facing a front surface, a sensor 39 is arranged.
- the end wall passing through conductor pieces form connecting lines for the sensor, which is produced for example by semiconductor technology or other methods, such as microelectronics.
- FIG. 12 A plug emerges, which in the example shown is at the end of a channel 40 filled with a fluid which is analyzed by capillary electrophoresis. At the other not visible end of the channel 40 there is another, the plug corresponding stopper shown with an electrode 41.
- the electrodes 41 of both plug generate an electric field of several 10 3 volts, in which the molecules in the fluid due to their size to different move quickly, so that a "separation" takes place. In some cases, high temperatures occur, which cause the fluid to outgas.
- the plugs therefore each have a degassing 42.
- Fig. 13 shows a stopper formed as a hollow body with an end wall 43 which is not injection molded like the rest of the stopper but is formed by a separate foil with continuous conductor pieces and functional electrodes on the front side.
- the foil welded to the rest of the plug is flexible and can be deflected into the channel region by mechanical or pneumatic actuation by means of an operating device in accordance with arrow 44. By such a deflection, the interaction between the electrodes and a sample liquid to be analyzed or processed can be intensified.
- a handling device 45 In a cavity of the plug, a handling device 45 is clamped with embedded connection conductors, which have contact with electrodes on the end face of the plug facing away from the handling device.
- the electrodes can be functionalized with antibodies, for example.
- the stopper is in a For example, immersed in a microtiter plate or other sample vessel 46 sample 47 immersed, with, for example, attach analytes to the plug.
- the attachment can be supported by stirring movements.
- the plug dips into a washing solution 48, for example.
- the plug can be transferred into a detection reagent 49, which allows an electrical readout of the electrodes.
- the plug could also have magnetic or electromagnetic means and be provided for use with functionalized magnetic beads as an alternative to antibodies applied directly to the plug.
- the magnetic beads can also be dispensed into the respective liquids and be resumed by electromagnetic actuation from the plug for further transport.
- Fig. 15 indicates how plugs with electrodes can be made efficiently.
- the carrier body produced by injection molding can be according to Fig. 15a store and hold eg in quantities of 10 to 1000 components in defined positions on a carrier 50.
- a via for example by a printing process, such as screen printing.
- separate end walls of silicon, glass, ceramic or plastic could be applied.
- a third step takes place according to Fig. 15c the formation of functional electrodes, eg by printing processes, such as screen printing or by thin-film processes or by laser processes.
- a fourth step Fig. 15d
- the plugs accumulated in large numbers can undergo surface functionalization, for example by antibodies or dry reagents or functionalized beads. This can be done by pipetting and subsequent drying. Alternatively, a passivation layer may be applied by a printing or thin-film process. Only in a last step ( Fig. 15e ), eg before assembly, a separation of the plugs must take place with removal from the magazine.
Priority Applications (4)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
EP16152755.1A EP3199240A1 (fr) | 2016-01-26 | 2016-01-26 | Cellule d'ecoulement microfluidique comprenant une electrode integree et son procede de fabrication |
PCT/EP2016/082748 WO2017129340A1 (fr) | 2016-01-26 | 2016-12-28 | Cellule à circulation microfluidique à électrode intégrée et son procédé de fabrication |
US16/070,125 US11433393B2 (en) | 2016-01-26 | 2016-12-28 | Microfluidic flow cell comprising an integrated electrode, and method for manufacturing same |
CN201680079923.8A CN108495713B (zh) | 2016-01-26 | 2016-12-28 | 包括集成电极的微流体流动池及其制造方法 |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
EP16152755.1A EP3199240A1 (fr) | 2016-01-26 | 2016-01-26 | Cellule d'ecoulement microfluidique comprenant une electrode integree et son procede de fabrication |
Publications (1)
Publication Number | Publication Date |
---|---|
EP3199240A1 true EP3199240A1 (fr) | 2017-08-02 |
Family
ID=55299232
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
EP16152755.1A Pending EP3199240A1 (fr) | 2016-01-26 | 2016-01-26 | Cellule d'ecoulement microfluidique comprenant une electrode integree et son procede de fabrication |
Country Status (4)
Country | Link |
---|---|
US (1) | US11433393B2 (fr) |
EP (1) | EP3199240A1 (fr) |
CN (1) | CN108495713B (fr) |
WO (1) | WO2017129340A1 (fr) |
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2020012263A1 (fr) * | 2018-07-09 | 2020-01-16 | Presens Precision Sensing Gmbh | Système d'analyse d'un échantillon de fluide |
Families Citing this family (1)
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- 2016-12-28 WO PCT/EP2016/082748 patent/WO2017129340A1/fr active Application Filing
- 2016-12-28 CN CN201680079923.8A patent/CN108495713B/zh active Active
- 2016-12-28 US US16/070,125 patent/US11433393B2/en active Active
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US20190022646A1 (en) | 2019-01-24 |
US11433393B2 (en) | 2022-09-06 |
WO2017129340A1 (fr) | 2017-08-03 |
CN108495713B (zh) | 2021-07-09 |
CN108495713A (zh) | 2018-09-04 |
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