EP3310481A1 - Dispositif de fonctionnalisation et de détection de surface - Google Patents

Dispositif de fonctionnalisation et de détection de surface

Info

Publication number
EP3310481A1
EP3310481A1 EP16730848.5A EP16730848A EP3310481A1 EP 3310481 A1 EP3310481 A1 EP 3310481A1 EP 16730848 A EP16730848 A EP 16730848A EP 3310481 A1 EP3310481 A1 EP 3310481A1
Authority
EP
European Patent Office
Prior art keywords
fluidic
fluidic channel
channel
fluid
coating
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
Application number
EP16730848.5A
Other languages
German (de)
English (en)
Inventor
Benjamin Jones
Tim Stakenborg
Paolo Fiorini
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Interuniversitair Microelektronica Centrum vzw IMEC
Original Assignee
Interuniversitair Microelektronica Centrum vzw IMEC
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 Interuniversitair Microelektronica Centrum vzw IMEC filed Critical Interuniversitair Microelektronica Centrum vzw IMEC
Priority claimed from PCT/EP2016/064217 external-priority patent/WO2016203051A1/fr
Publication of EP3310481A1 publication Critical patent/EP3310481A1/fr
Pending legal-status Critical Current

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
    • B01L3/502707—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
    • F—MECHANICAL ENGINEERING; LIGHTING; HEATING; WEAPONS; BLASTING
    • F16—ENGINEERING ELEMENTS AND UNITS; GENERAL MEASURES FOR PRODUCING AND MAINTAINING EFFECTIVE FUNCTIONING OF MACHINES OR INSTALLATIONS; THERMAL INSULATION IN GENERAL
    • F16K—VALVES; TAPS; COCKS; ACTUATING-FLOATS; DEVICES FOR VENTING OR AERATING
    • F16K99/00—Subject matter not provided for in other groups of this subclass
    • F16K99/0001—Microvalves
    • F16K99/0003—Constructional types of microvalves; Details of the cutting-off member
    • F16K99/0021—No-moving-parts valves
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J2219/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
    • B01J2219/00274—Sequential or parallel reactions; Apparatus and devices for combinatorial chemistry or for making arrays; Chemical library technology
    • B01J2219/00277—Apparatus
    • B01J2219/00351—Means for dispensing and evacuation of reagents
    • B01J2219/00353—Pumps
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J2219/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
    • B01J2219/00274—Sequential or parallel reactions; Apparatus and devices for combinatorial chemistry or for making arrays; Chemical library technology
    • B01J2219/00277—Apparatus
    • B01J2219/00351—Means for dispensing and evacuation of reagents
    • B01J2219/00389—Feeding through valves
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J2219/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
    • B01J2219/00274—Sequential or parallel reactions; Apparatus and devices for combinatorial chemistry or for making arrays; Chemical library technology
    • B01J2219/00277—Apparatus
    • B01J2219/00351—Means for dispensing and evacuation of reagents
    • B01J2219/00414—Means for dispensing and evacuation of reagents using suction
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J2219/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
    • B01J2219/00274—Sequential or parallel reactions; Apparatus and devices for combinatorial chemistry or for making arrays; Chemical library technology
    • B01J2219/00277—Apparatus
    • B01J2219/00351—Means for dispensing and evacuation of reagents
    • B01J2219/00418—Means for dispensing and evacuation of reagents using pressure
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J2219/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
    • B01J2219/00274—Sequential or parallel reactions; Apparatus and devices for combinatorial chemistry or for making arrays; Chemical library technology
    • B01J2219/00583—Features relative to the processes being carried out
    • B01J2219/00603—Making arrays on substantially continuous surfaces
    • B01J2219/00605—Making arrays on substantially continuous surfaces the compounds being directly bound or immobilised to solid supports
    • B01J2219/00632—Introduction of reactive groups to the surface
    • B01J2219/00637—Introduction of reactive groups to the surface by coating it with another layer
    • 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
    • B01L2300/0636—Integrated biosensor, microarrays
    • 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
    • B01L2300/00—Additional constructional details
    • B01L2300/16—Surface properties and coatings
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2400/00—Moving or stopping fluids
    • B01L2400/04—Moving fluids with specific forces or mechanical means
    • B01L2400/0403—Moving fluids with specific forces or mechanical means specific forces
    • B01L2400/0406—Moving fluids with specific forces or mechanical means specific forces capillary forces
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2400/00—Moving or stopping fluids
    • B01L2400/06—Valves, specific forms thereof
    • B01L2400/0688—Valves, specific forms thereof surface tension valves, capillary stop, capillary break
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2400/00—Moving or stopping fluids
    • B01L2400/08—Regulating or influencing the flow resistance
    • B01L2400/084—Passive control of flow resistance
    • B01L2400/086—Passive control of flow resistance using baffles or other fixed flow obstructions
    • 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
    • B01L3/502738—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip characterised by integrated valves
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L3/00—Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
    • B01L3/50—Containers for the purpose of retaining a material to be analysed, e.g. test tubes
    • B01L3/502—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures
    • B01L3/5027—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip
    • B01L3/502746—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip characterised by the means for controlling flow resistance, e.g. flow controllers, baffles

Definitions

  • the invention relates to fluidic devices.
  • it relates to methods and fluidic devices for coating inner surfaces of fluidic channels and for detecting an analyte in a fluid sample.
  • Biosensors often make use of molecules such as antibodies coupled to a surface to detect an analyte in a fluid sample.
  • a coating fluid comprising antibodies that bind to that surface is flown over the surface.
  • Such a surface is called a functionalized surface or a functionalized sensor region.
  • a sample fluid containing the analyte is then directed to flow over the functionalized sensor region for performing detection.
  • Functionalization of the sensor region should advantageously be restricted to the sensing region.
  • the analyte present in the sample fluid is distributed over that region leading to depletion of the analyte. This decreases the sensitivity of the assay.
  • a fluidic device for locally coating an inner surface of a fluidic channel comprising: a first, a second and a third fluidic channel intersecting at a common junction, the first fluidic channel being connectable to a coating fluid reservoir and the third fluidic channel being connectable to a sample fluid reservoir; characterized in that the fluidic device further comprises a fluid control means configured for creating a fluidic flow path for a coating fluid at the common junction such that, when coating, a coating fluid propagates from the first to the second fluidic channel via the common junction without propagating or leaking into the third fluidic channel.
  • the fluidic device further comprises a fourth fluidic channel also intersecting at the common junction
  • the fluid control means is configured for creating a fluidic flow path for a coating fluid at the common junction such that, when coating, a coating fluid propagates from the first to the second fluidic channel via the common junction, without propagating or leaking into the third fluidic channel and the fourth fluidic channel.
  • the fluid control means is a pump system.
  • the pump system is configured to create an inward flow in the third and the fourth fluidic channel, towards the common junction.
  • the fluidic control means is a capillary system.
  • the capillary system comprises: a capillary pump coupled to the second fluidic channel; and the resistivity of the first and the second fluidic channel and the capillary pressure in the capillary pump and in the third and fourth channels are adapted such that the coating fluid does not flow into the third or the fourth channel when propagating from the first to the second fluidic channel, via the common junction.
  • the third fluidic channel having an inlet for receiving the sample fluid and the second fluidic channel having an outlet for discharging fluid downstream from said inlet;
  • the fluidic control means comprises a first fluidic structure located in the third fluidic channel between the common junction and the inlet; and the first fluidic structure is configured such that when a coating fluid propagates from the first fluidic channel into the second fluidic channel, the coating fluid only propagates to the outlet thereby at least partly coating an inner surface of the second fluidic channel and the common junction.
  • the fluidic control means further comprises a second fluidic structure located in the first fluidic channel and configured for sealing the first fluidic channel when a fluid sample propagates from the inlet to the outlet, thereby preventing the fluid sample from entering the first fluidic channel.
  • the first fluidic structure is a one-way capillary valve.
  • the second fluidic structure is a one-way capillary valve.
  • a sensing system for sensing an analyte comprising: a fluidic device according to the first aspect of the invention or according to any of its embodiments; a sensor positioned for sensing an analyte in a fluid sample propagating through the fluidic device.
  • a method for partly coating a surface of a fluidic channel comprising: providing a fluidic device having a first, a second and a third fluidic channel intersecting at a common junction; propagating a coating fluid from the first to the second fluidic channel, via the common junction, thereby coating the common junction and at least a portion of the second fluidic channel; characterized in that: while propagating the coating fluid, creating a fluidic flow path at the common junction such that the coating fluid does not propagate or leak into the third channel.
  • the fluidic device comprises a fourth fluidic channel also intersecting at the common junction and wherein creating a fluidic flow path comprises creating an inward flow in the third and in the fourth fluidic channel, towards the common junction.
  • creating a fluidic flow path comprises adapting the resistivity of the first fluidic channel, the resistivity of the second fluidic channel, and the pressure in the second fluidic channel.
  • a method for sensing an analyte in a fluid sample comprising: performing all steps of the method according to the third aspect of the invention or according to any of its embodiments; thereafter sealing the first fluidic and optionally the second fluidic channel; propagating a sample fluid from the third fluidic channel through the fluidic device; and performing sensing of the analyte at least at the coated common junction.
  • FIG. 1 illustrates a fluidic device according to an embodiment of the invention.
  • FIG. 2 illustrates a system comprising a row of interconnected fluidic devices according to embodiments of the invention.
  • FIG. 3 illustrates a system comprising a matrix of interconnected fluidic devices according to embodiments of the invention.
  • FIG. 4 illustrates a capillary fluidic device according to an embodiment of the invention.
  • FIG. 5 illustrates an equivalent fluidic resistor network for the embodiment illustrated in FIG. 4.
  • FIG. 6 illustrates a fluidic device according to an embodiment of the invention
  • FIG. 7 illustrates a fluidic device according to an embodiment of the invention
  • FIG. 8 illustrates a cross section of the fluidic device illustrated in FIG. 7
  • FIG. 9 illustrates a fluidic device according to an embodiment of the invention
  • FIG. 10 illustrates a sensing system according to an embodiment of the invention
  • FIG. 11 illustrates a capillary flow device according to an embodiment of the invention
  • coating fluid refers to a fluid comprising components that are capable of binding to a substrate surface, e.g. a silicon-based, plastic, metal or any other suitable surface.
  • the components may have properties such as specific binding or hydrophilic/hydrophobic properties, or other properties.
  • the components may be any binding element allowing the coupling of a target site-specific to a surface. Such elements may be antibodies or enzymes.
  • Fluid sample may refer to a body fluid that can be isolated from the body of an individual. Such a body fluid may refer to, but not limited to, blood, plasma, serum, bile, saliva, urine, tears, perspiration. Fluid sample may also refer to any fluid suitable for transporting objects or components in a fluidic or micro-fluidic system.
  • buffer fluid may refer to a fluid that does not react with or elute a surface coating created by the coating fluid or react with or prevent the analyte from binding with the surface coating.
  • the buffer fluid can also be two separate, optionally different, fluids.
  • the technical objective problem stated above is solved by localizing binding elements, e.g. antibodies, to a specific limited area of a surface, for example a sensing surface of a sensor. By doing so, depletion of an analyte in a fluid sample flowing over that region is minimized because of the local presence of antibodies. This increases the sensitivity of the assay.
  • binding elements e.g. antibodies
  • application of the antibodies prior to bonding is not possible since the antibodies will not survive the required bonding temperatures.
  • solving the technical objective problem is further complicated when dealing with closed fluidic channels of which a particular area of inner surfaces of fluidic channels must be coated.
  • a cross-flow fluidic device that comprises at least three fluidic channels intersecting at a junction. Some fluidic channels are used for coating a particular area of inner surfaces of the fluidic device present at the junction. Other fluidic channels are used to flow a fluid sample over that particular area such that, for example, sensing of an analyte in the fluid sample can be performed at the junction.
  • the device is configured such that when a coating fluid flows from one fluidic channel to another fluidic channel via the junction, the coating fluid does not propagate or leak into the other fluidic channel(s).
  • This restriction of the fluid flow is realized by for example either a pump system, a capillary system or a passive valve system which is configured to achieve that effect.
  • a fluidic device 100 for locally coating an inner surface of a fluidic channel comprises a first 101, a second 102 and a third 103 fluidic channel intersecting at a common junction 105.
  • the fluidic channels may be micro-fluidic channels.
  • the common junction 105 is defined as the inner area of the device common or shared by all fluidic channels 101, 102, 103.
  • a fluid flowing from one fluidic channel to another fluidic channel always flows over/via the junction 105.
  • this coating fluid coats at least the surface area at the common junction 105.
  • a particular area of the fluidic device can be coated with, for example, components for binding an analyte such as antibodies capable of binding an antigen.
  • the first fluidic channel 101 is connectable to a coating fluid reservoir and the third fluidic channel 103 is connectable to a fluid sample reservoir.
  • the fluidic device 100 further comprises a fluid control means 111 configured for creating, during the coating, a fluidic flow path for a coating fluid at the common junction 105. Creating the fluidic flow path ensures that a coating fluid propagating from the first 101 to the second 102 fluidic channel, via the common junction 105, does not propagate into the third 103 fluidic channel.
  • This fluidic flow path may be created by flowing a buffer fluid towards the common junction through fluidic channels not used to flow the coating fluid.
  • the fluidic control means may comprise a pump system. Such a pump system is adapted to create an inward flow using the buffer fluid, towards the common junction.
  • the fluid control means 111 may be further configured for creating, when not coating, at least a temporary fluid flow barrier. Creating the at least a temporary fluid flow barrier ensures that a fluid sample provided in the third fluidic channel 103 and propagating in the fluidic device does not propagate into the first fluidic channel 101.
  • the fluidic control means 111 may comprise one or more valves suitable for shutting the appropriate channels.
  • a coating fluid provided to the fluidic device 100 can propagate through the device thereby at least partly coating an inner surface of a fluidic channel of the device 100.
  • the inner surface being one or more inner surfaces of the device forming the common junction 105.
  • a fluid sample can propagate through the device, e.g. by use of a pump, such that the fluid sample flows over the partly coated inner surface of the fluidic channel. It is an advantage of the invention that instead of coating the complete inner surface of a fluidic channel, an inner surface of a fluidic channel can be partly coated with a coating fluid.
  • the fluidic device 100 presented in this invention prevents propagation of the coating fluid into channels which are not used for coating (e.g. the first fluidic channel in FIG. 1). This is an important advantage as it limits diffusion of the coating material (e.g. antibodies) contained within the coating fluid into those channels. Generally the fluid composing the coating fluid and buffer fluid is the same. What is dissolved into the coating fluid (the coating material) should not diffuse too far away from, for example, a detection zone (e.g. a biosensor).
  • a detection zone e.g. a biosensor
  • the structure of the fluidic device 100 allows all fluidic channels to be closed fluidic channels. This in contrast to prior art devices in which fluidic channels must be open to allow the coating, e.g. by external spotting, of particular areas of inner surface of the fluidic channels.
  • the fluidic device further comprises a fourth 104 fluidic channel also intersecting at the common junction 105.
  • the fluid control means 111 is configured for creating a fluidic flow path for a coating fluid at the common junction 105 such that, when coating, a coating fluid propagates from the first 101 to the second 102 fluidic channel via the common junction 105, without propagating into the third 103 fluidic channel and the fourth 104 fluidic channel.
  • the fluid control means 111 is further configured for creating at least a temporary fluid flow barrier such that, when not coating, a fluid sample propagating from the third 103 to the fourth 104 fluidic channel does not propagate into first 101 and/or the second 102 fluidic channel.
  • FIG. 1 illustrates such an embodiment.
  • FIG. 1 illustrates a fluidic device 100 according to an embodiment of the invention.
  • the device 100 comprises a first 101, a second 102, a third 103 and a fourth 104 fluidic channel. All four fluidic channels intersect at the common junction 105.
  • a fluidic control means 111 is coupled to the third 103 and the fourth 104 fluidic channel.
  • the fluidic control means 111 is active and the coating fluid will only propagate from the first 101 to the second 102 fluidic channel and not propagate into the third 103 and the fourth 104 fluidic channel.
  • a fluid sample may then propagate from the third 103 to the fourth 104 fluidic channel, over the common junction 105.
  • the fluid control means 111 may comprise a means for sealing the fluidic channels used for coating.
  • the means for sealing fluidic channels may be one or more valves.
  • the fluid control means 111 can seal one or more fluidic channels which are used for performing the coating, in close proximity of the common junction 105.
  • the fluidic control means 111 comprises a means for sealing the first 101 and the second 102 fluidic channel. By sealing these channels, the fluid sample does not propagate into first 101 and the second 102 fluidic channels.
  • depletion of the analyte in the fluid sample does not occur and sensitivity of the assay in the fluidic device is increased.
  • an array of fluidic devices 100, 100', 100", corresponding with fluidic devices as illustrated in FIG. 1, are fluidically interconnected.
  • the array may be a ID array.
  • Such a ID array comprises a row of fluidic device 100 of which the fluidic channels 101, 102, 101', 102', 101", 102", which are used to coat the common junctions 105, 105', 105" of each fluidic device 100, are fluidically connected such that a single sample of coating fluid can propagate through the fluidic channels 101, 102, 101', 102', 101", 102" and coat all common junctions 105, 105', 105".
  • the same coating fluid can be used to coat different common junctions 105, 105', 105". It is an advantage of the invention that it is not necessary to individually perform the coating of different common junctions 105, 105', 105". This simplifies and reduces time to perform the coating.
  • the system of FIG. 2 illustrates such a ID array. It comprises three fluidic devices 100, 100', 100". Fluidic channel 102 is fluidically connected to fluidic channel 101'. Fluidic channel 102' is fluidically connected to fluidic channel 101". A coating fluid provided in fluidic channel 101 can propagate all the way down to fluidic channel 102", via common junctions 105, 105', 105". During the propagation, the common junctions 105, 105', 105" are coated by the same coating fluid.
  • the array may also be a 2D array.
  • the fluidic channels used to coat the common junctions are fluidically interconnected such that the common junctions of the fluidic devices in each row can be coated with the same coating fluid.
  • common junctions of different rows can be coated with different coating fluids.
  • the fluidic channels used to propagate a fluid sample are fluidically interconnected such that a fluid sample may flow from one row to another row via common junctions.
  • the system of FIG. 3 illustrates such a 2D array. It comprises six fluidic devices 100, 100', 100", 100a, 100a', 100a".
  • Fluidic channel 102 is fluidically connected to fluidic channel 10 .
  • Fluidic channel 102' is fluidically connected to fluidic channel 101".
  • a coating fluid provided in fluidic channel 101 can propagate all the way down to fluidic channel 102", via common junctions 105, 105', 105". During the propagation, the common junctions 105, 105', 105" are coated by the same coating fluid.
  • Fluidic channel 102a is fluidically connected to fluidic channel 101a'.
  • Fluidic channel 102a' is fluidically connected to fluidic channel 101a".
  • a coating fluid provided in fluidic channel 101a can propagate all the way down to fluidic channel 102a", via common junctions 105a, 105a', 105a". During the propagation, the common junctions 105a, 105a', 105a" are coated by the same coating fluid.
  • Fluidic channel 104 is fluidically connected to fluidic channel 103a.
  • Fluidic channel 104' is fluidically connected to fluidic channel 103a'.
  • Fluidic channel 104" is fluidically connected to fluidic channel 103a".
  • a fluid sample may be introduced into fluidic channel 103 and propagate all the way to fluidic channel 104a, via common junctions 105, 105a.
  • Another fluid sample may be introduced into fluidic channel 103' and propagate all the way to fluidic channel 104a', via common junctions 105', 105a'. Yet another fluid sample may be introduced into fluidic channel 103" and propagate all the way to fluidic channel 104a", via common junctions 105", 105a".
  • two different coating fluids may be introduced in the device to perform coating of the common junctions and three different fluid samples may be introduced wherein each fluid sample can flow over a differently coated common junction.
  • the fluid control means 111 comprises a pump system.
  • the pump system is configured to create an inward flow rate in fluidic channels, towards the common junction.
  • a buffer fluid may be used.
  • the flow rate may be inwards from different sides while allowing for a fluidic flow path for a fluid flowing through the common junction, via fluidic channels 101 and 102.
  • the pump system creates a flow rate in the third 103 and the fourth 104 fluidic channel towards the common junction 105.
  • the amount of flow rate applied is selected such that propagation of a coating fluid from the first 101 to the second 102 fluidic channel is possible and propagation of the coating fluid in the third 103 or the fourth 104 fluidic channel minimized.
  • the amount of the flow rate can be determined experimentally by using, for example, dye coloured fluids which allow observing when the diffusion flow rate is balanced by the flow rate created by the fluid control means 111.
  • the fluidic control means 111 is a capillary system.
  • the coating is performed solely using capillary forces.
  • FIG. 4 The device comprises a first 101 , a second 102, a third 103 and a fourth 104 fluidic channel. These fluidic channels intersect at a common junction 105.
  • the first fluidic channel 101 is connected to an inlet 108 for providing a coating fluid in the first fluidic channel 101.
  • the first 101 and the second 102 fluidic channels are fluidic channels having capillary dimensions. Thus, the dimensions of these channels, typically ranging from sub-micron to millimetre scale, are selected such that they are suitable for use in a capillary system.
  • the second fluidic channel 102 is fluidically connected to a capillary pump 107 adapted to suck a coating fluid present in the first fluidic channel 101 into the second 102 fluidic channel.
  • the resistivity of the first 101 and the second 102 fluidic channel and the capillary pressure in the capillary pump 107 and in the third 103 and fourth 104 channels are adapted, e.g. by selecting appropriate channel diameters, such that the coating fluid does not propagate into the third 103 or the fourth 104 channel when propagating from the first 101 to the second 102 fluidic channel, via the common junction 105. It is an advantage of the invention that such an embodiment does not require active components such as valves or active pumps. This reduces power consumption and cost of the complete device.
  • the first fluidic channel has a high resistivity
  • the second fluidic channel has a low resistivity.
  • the resistivity of the first fluidic channel 101 may be between 10 s and 10 26 Pa «s/m 3 /m of channel length.
  • the resistivity of the second fluidic channel 102 may also be between 10 s and 10 26 Pa «s/m 3 /m of channel length.
  • the relative resistances of channel 101 and 102 must be such that equation (4) is satisfied.
  • the capillary pressure of the pump may be between 100 Pa and 1 MPa. It is important that the capillary pressure in channel 103 and 104 is lower than the capillary pressure in the pump.
  • the resistivity of the first fluidic channel 101 is 10 19 Pa «s/m 3 .
  • the resistivity of the second fluidic channel 102 is 5xl0 17 Pa «s/m 3 .
  • the capillary pressure of the pump is about 5 kPa.
  • the capillary pressure in channels 103 and 104 is about 2 kPa.
  • the first fluidic channel 101 is shaped such that the resistivity of the first fluidic channel 101 is increased.
  • the first fluidic channel 101 may comprise a fluidic structure 112 adapted to increase the resistivity of the first fluidic channel 101.
  • the fluidic structure 112 may be meander-shaped.
  • the dimensions of the second fluidic channel 102 are selected such that the resistivity of the second fluidic channel 102 is lower than the resistivity of the first fluidic channel 101.
  • At least a part of the second fluidic channel 102 may be shaped such that the resistivity of the second fluidic channel 102 is lower than the resistivity of the first fluidic channel 101.
  • FIG. 5 shows an equivalent fluidic resistor network for the embodiment illustrated in FIG. 4.
  • the capillary pump 107 flow rate is:
  • the pressure drop, Hp, hydraulic resistance, R, and flow rate, Q are related by:
  • Equation (4) thus gives a condition that must be satisfied to ensure that the coating fluid does not propagate into the third 103 and the fourth 104 fluidic channels during capillary pumping. A further condition arises while the capillary system is filling with the coating liquid prior to entering the low resistance channel.
  • the common junction 105 must easily wet and bring the fluid to the second fluidic channel 102 without entering the third 103 and the fourth 104 fluidic channels. This is satisfied if P DET ⁇ PCHAN > E - the capillary pressure in the common junction 105 must be stronger than the capillary pressure in the third and the fourth fluidic channels, and PPUMP ⁇ PCHAN-
  • the capillary pressure in a rectangular channel is given by:
  • ⁇ is the surface tension
  • W c is the channel width
  • H c is the channel height
  • ⁇ is the contact angle between the liquid-vapor interface and the solid surfaces of the channel wall.
  • the diameter of the reservoir is 2mm.
  • the first fluidic channel 101 is 5 Elm wide by 200 Elm deep by 20 mm long.
  • the second fluidic channel 102 is 5 Elm wide by 200 Elm deep by 1 mm long.
  • the common junction 105 comprises micropillars with 24 Elm diameter and 30 Elm pitch.
  • the third fluidic channel 103 is 100 Elm wide by 200 Elm deep.
  • the fourth fluidic channel 104 is 100 Elm wide by 200 Elm deep.
  • the capillary pump 107 comprises an array with micropillars having 24 Elm diameter and 30 Elm pitch. The dimension of the array is 3 mm by 3 mm. Downstream of the micropillars of the capillary pump, an outlet vent with a diameter of 1 mm is present.
  • the first and/or the second fluidic channels comprises a restriction 113, 114.
  • a restriction is a portion of the fluidic channel that is narrower compared to the rest of the fluidic channel.
  • FIG. 6 illustrates such an embodiment.
  • FIG. 6 illustrates the same embodiment as FIG. 1 but the first 101 and the second 102 fluidic channel now each feature a restriction 113, 114.
  • the third fluidic channel 103 comprises an inlet 108 for receiving the fluid sample and the second fluidic channel 102 comprises an outlet 109 for discharging the fluid sample downstream from said inlet 108.
  • the fluid control means 111 comprises a first fluidic structure 107 located in the third fluidic channel 103, in between the common junction 105 and the inlet 108.
  • the first fluidic structure 107 is configured such that when a coating fluid propagates from the first fluidic channel 101 into the second fluidic channel 102, the coating fluid only propagates to the outlet 109 thereby coating the common junction 105 and at least partly coating an inner surface of the second fluidic channel 102.
  • the fluidic structure 107 is configured to block a fluid from propagating from the common junction 105 towards the inlet 108.
  • the fluidic structure 107 functions as a one-way check valve preventing any fluid propagating towards the inlet 108, from the common junction 105.
  • only the common junction 105 and second fluidic channel 102 are coated by a coating fluid provided in the first fluidic channel 101.
  • FIG. 7 illustrates such an embodiment.
  • FIG. 7 illustrates a fluidic device comprising three fluidic channels 101, 102, 103.
  • the three fluidic channels 101, 102, 103 intersect at a common junction 105.
  • the third fluidic channel 103 has an inlet 108 for providing a fluid sample in the third fluidic channel 103.
  • the second fluidic channel has an outlet 109 for exiting a fluid sample.
  • a fluidic structure 107 is located in the third fluidic channel, in between the inlet 108 and the common junction 105.
  • the fluidic structure 107 is configured to block a fluid from propagating from the common junction 105 to the inlet 108 but allows a fluid to propagate from the inlet 108 to the common junction 105.
  • the fluidic structure 107 is a unidirectional fluidic structure.
  • the fluidic structure 107 is a oneway capillary valve.
  • An implementation of a one-way capillary valve may be an abrupt change in the geometry of an inner surface of the third fluidic channel 103.
  • the upper wall facing the inner surface comprising the abrupt change in geometry may be hydrophobic.
  • at least the fluidic channel comprising the one-way capillary valve is open such that there is no top wall or cover.
  • the abrupt change may be a sudden height difference in the inner surface of the third fluidic channel 103.
  • Such a sudden height difference is illustrated in the cross sectional view in FIG. 8 that illustrates cross-section A-A' of FIG. 7.
  • the fluid control means 111 may further comprise a means for sealing the first fluidic channel 101 when a fluid sample propagates from the inlet 108 to the outlet 109 to prevent the fluid sample from entering the first fluidic channel 101 which would lead to depletion of an analyte in the fluid sample.
  • a means may e.g. be a valve.
  • the first fluidic channel 101 comprises a one-way capillary valve. This one-way capillary valve is positioned such that a fluid, e.g. a coating fluid, provided in the first fluidic channel 101 is allowed to propagate to the common junction 105. A fluid sample propagating from the inlet 108 to the outlet 109, is blocked from propagating from the common junction 105 into the first fluidic channel 101 by this one-way capillary valve.
  • a sensing system can be used to detect an analyte in a fluid sample.
  • the sensing system comprises a fluidic device 100 as presented in the first aspect of the invention or according to any of its embodiments.
  • the sensing system further comprises a sensor 106 positioned at/near the inner surfaces of the fluidic device 100 which can be coated.
  • the sensor is capable of sensing an analyte in a fluid sample.
  • the sensor 106 may be a biosensor, e.g. an affinity based sensor.
  • the sensor 106 may also be an image sensor.
  • the sensor 106 is positioned at the common junction 105.
  • the sensor 106 may be integrated in an inner surface of fluidic channels of the fluidic device 100.
  • the sensor 106 may be integrated in an inner surface of the fluidic device 100 such that, in a first step, a top surface of the sensor 106 can be coated with a coating fluid. In a second step, a fluid sample may be flown over that coated top surface and detection of an analyte bound to or present at the coated top surface may be performed by the sensor 106.
  • the sensor 106 may be positioned such that light, e.g. fluorescent signals, from a coated inner surface can be received by the sensor 106.
  • an image sensor may be positioned such that its sensing side is exposed to light signals originating from a coated surface of the device.
  • the sensor 106 may be positioned adjacent to coated surfaces, for example at the common junction, such that light signals can be received.
  • FIG. 10 illustrates an embodiment of the invention comprising a sensor 106.
  • FIG. 10 features a similar embodiment as illustrated in FIG. 1.
  • the system further comprises a sensor 106 positioned at the common junction 105.
  • the inner surfaces of the second fluidic channel 102 are coated with a coating fluid propagating from the first 101 to the second 102 fluidic channel.
  • the sensor 106 may be positioned at the common junction 105 and at the inner surfaces of fluidic channel 102.
  • a method for partly or locally coating a surface of a fluidic channel comprises, in a first step, providing a fluidic device 100 having a first 101, a second 102 and a third 103 fluidic channel intersecting at a common junction 105.
  • a coating fluid is propagated from the first 101 to the second 102 fluidic channel, via the common junction 105.
  • at least the common junction 105 is coated by the coating fluid.
  • the areas of the inner surfaces of the fluidic channels forming this common junction 105 are coated.
  • a fluidic flow path is created at the common junction 105 such that the coating fluid does not propagate into the third 103 channel.
  • the fluidic device 100 further comprises a fourth fluidic channel 104, also intersecting at the common junction 105.
  • Creating the fluidic flow path comprises creating an inward flow in the third 103 and the fourth 104 fluidic channel, towards the common junction 105.
  • Creating the inward flow may be achieved by flowing a buffer fluid towards the common junction 105. For example, flowing the buffer fluid in the third 103 and the fourth 104 fluidic channel, towards the common junction 105.
  • the fluidic device 100 further comprises a fourth fluidic channel 104, also intersecting at the common junction 105, and creating a fluidic flow path comprises adapting the resistivity of the first 101, the resistivity of the second 102 fluidic channel, and the pressure in the second 102 fluidic channel.
  • the method may also comprise a step of sealing the fluidic channels used to propagate the coating fluid.
  • a method for sensing an analyte in a fluid sample comprising performing, in a first step, all steps of the method as described in the third aspect of the invention or according to any of its embodiments.
  • a fluid sample is propagated from the third fluidic channel 103 through the fluidic system. While the fluid sample is propagated through the fluidic device, it flows over the common junction 105 and sensing of the analyte in the fluid sample at the coated common junction 105 is performed.
  • the method as described in the fourth aspect of the invention may be implemented using the sensing system as described in the second aspect of the invention, or according to any of its embodiments.
  • the present invention also relates to the use of a fluidic structure as described in the first aspect for coating a particular area, e.g. a sensing region.

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  • Chemical & Material Sciences (AREA)
  • Dispersion Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • General Engineering & Computer Science (AREA)
  • Analytical Chemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Hematology (AREA)
  • Clinical Laboratory Science (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Mechanical Engineering (AREA)
  • Automatic Analysis And Handling Materials Therefor (AREA)

Abstract

L'invention concerne un dispositif fluidique (100) permettant un revêtement local d'une surface interne d'un canal fluidique. Le dispositif fluidique (100) comprend des premier (101), deuxième (102) et troisième (103) canaux fluidiques se croisant au niveau d'une jonction commune (105). Le premier canal fluidique peut être raccordé à un réservoir de fluide de revêtement et le troisième canal fluidique peut être raccordé à un réservoir de fluide d'échantillon. Le dispositif fluidique (100) comprend en outre un moyen de commande de fluide (111) configuré pour créer un trajet d'écoulement fluidique pour un fluide de revêtement au niveau de la jonction commune (105) de sorte que, lors du revêtement, un fluide de revêtement se propage du premier canal fluidique (101) vers le deuxième canal fluidique (102) par le biais de la jonction commune (105) sans se propager dans le troisième canal fluidique (103). L'invention concerne également un procédé correspondant pour le revêtement et la détection.
EP16730848.5A 2015-06-19 2016-06-20 Dispositif de fonctionnalisation et de détection de surface Pending EP3310481A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
EP2015172909 2015-06-19
PCT/EP2016/064217 WO2016203051A1 (fr) 2015-06-19 2016-06-20 Dispositif de fonctionnalisation et de détection de surface

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EP3310481A1 true EP3310481A1 (fr) 2018-04-25

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EP (1) EP3310481A1 (fr)

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