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
  • B01L3/502746—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
• • 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
• • 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
  • F16K99/0017—Capillary or surface tension valves, e.g. using electro-wetting or electro-capillarity effects
• • 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
• • 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
  • B01L2300/0887—Laminated structure
• • 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
  • B01L2400/08—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
• • 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
  • F16K2099/0082—Microvalves adapted for a particular use
  • F16K2099/0084—Chemistry or biology, e.g. "lab-on-a-chip" technology

Definitions

• the present invention relates to the field of devices for handling liquid samples.
• Devices for handling liquid samples of various kinds are desirable to use for instance within point of care analyses. Moreover such devices can be used to analyse various samples including of blood, plasma, serum, sweat, saliva, urine, lachrymal fluid, water samples, and suspensions or solutions of food samples.
• Another problem is how to accurately and reproducible define a certain volume of sample which passes the analysis point before the reagent reaches the analysis point. [0010] Another problem is how to let the sample react at the analysis point for a prolonged time before the reagent reaches the analysis point.
• a further problem is to eliminate effects from the fact the reagent may dissolve differently depending on for instance age of the reagent and how dry the reagent is.
• the measured signal in some assays depends on the amount of reagent and the amount of sample. In many assays some kind of particles and/or some kind of molecules are detected and therefore the sample volume must be well defined.
• a device for handling liquid samples comprising: a) projections substantially perpendicular to the surface of said device, said projections having a height, diameter and a distance between the projections capable of generating capillary flow, lateral to said surface, of a fluid, b) at least one zone for receiving a sample, c) at least one sink with a capacity of receiving said liquid, said at least one sink exerting at least two different capillary forces on said liquid, d) at least two flow paths connecting said at least one zone for receiving a sample and said at least one sink, said flow paths exerting at least two different capillary forces on said liquid, e) at least one connection between said at least two flow paths.
• the assay device utilises projections substantially perpendicular to the surface to create a capillary force so that the liquid flows.
• the device utilises the fact that the capillary force can be different for different flow channels depending on the distance, geometry, diameter, and height of the projections. The difference in capillary force is used to direct the flow in the desired direction.
• Also encompassed within the present invention is a method of analysing a sample as well as a kit of parts.
• Advantages of the present invention include that it is possible to let a sample reach an analysis point before a reagent. Another advantage is that it is possible to define a certain volume of sample that passes an analysis point before the reagent reaches the analysis point. A further advantage is that it is possible to eliminate or alleviate effects from reagents which dissolve differently.
• Fig 1a-d depicts various embodiments of devices according to the present invention.
• Fig 2a-d depicts various stages during use of a device according to the present invention.
• Fig 3 is an electron micrograph of a part of an analysis device according to the present invention. It depicts a cross of two flow channels as used for instance in the device depicted in Fig 2.
• Fig 4 depicts a section of a flow channel comprising a gate which can be used in an assay device according to the present invention.
• Analysis point is used herein to denote a point or an area on an assay device where a measurement is performed.
• Analyte is used herein to denote a substance, chemical constituent, or biological constituent that is analysed.
• Reagent is used herein to denote a chemical or biological constituent participating in the analysis.
• Sample is used herein to denote any matter comprising an analyte.
• the assay device utilises projections substantially perpendicular to the surface to create a capillary force so that the liquid flows.
• the assay device assay utilises the fact that the capillary force can be different for different flow channels depending on the distance, geometry, diameter, and height of the projections. The difference in capillary force is used to direct the flow in the desired direction.
• the device for handling liquid samples comprises one zone for receiving a sample, shown as the circular zone.
• a reactant is dried onto the substrate on the area marked with a "k”.
• the embodiment further comprises a gate, which allows flow of liquid when it is in contact with liquid from at least two directions, indicated with a "g” in Fig 1.
• a gate only allows a flow of liquid when it is in contact with liquid from more that one side.
• An example of a gate which can be used in the present invention is depicted in Fig 4. It must be noted that the gates which can be used in the present invention is not limited to the gate depicted in Fig 4. Any type of gate can be used which blocks flow of liquid when it is in contact with liquid from one side only and which allows flow of liquid when it is in contact with liquid from more than one side.
• Any type of gate can be used which blocks flow of liquid when it is in contact with liquid from one side only and which allows flow of liquid when it is in contact with liquid from more than one side.
• the gate comprises projections with adjusted positions, distance, geometry, diameter, and height.
• the flow in at least one of the flow paths is made slower than in the other by making the flow path longer and/or lowering the capillary force exerted on the liquid.
• the distance, geometry, diameter, and height of the projections is adapted so that the capillary force is higher in the at least a part of the flow path and one of the sinks as compared to the flow path leading to the other sink.
• at least one reagent is adsorbed on the surface of at least one of the flow paths.
• the reagent is adsorbed on the flow path which exerts the lowest capillary force.
• the flow paths exerting different capillary force on the liquid have in one embodiment different flow rates for the liquid, due to the different capillary force.
• FIG. 3 One embodiment of the cross of flow paths in Fig 2 is depicted in Fig 3 and consists in this particular embodiment of projections with different space to create different capillary force.
• Fig 1 a there are two different sinks exerting different capillary forces on the liquid.
• Fig 1d there is one sink divided into two parts which are exerting different capillary force on the liquid. The border between the parts is indicated with a dashed line in Fig 1d.
• a substance is adsorbed and/or bound to the analysis point.
• such a substance has the capability to bind to at least one analyte.
• examples of such a substance include an antibody.
• at least one reagent is adsorbed or dried onto at least one flow channel.
• Such a reagent can be any chemical or biological entity that is participating in an analysis.
• examples of reagents include antibodies, antibodies comprising a detectable entity, other detectable molecules, and molecules with the ability to bind to an analyte.
• Fig 1c Such an embodiment is shown in Fig 1c, where two separate reagents k and k' are added after each other.
• at least three different capillary forces are exerted on said liquid; a first capillary force form a first sink, a second capillary force form a second sink and a third capillary force from a third sink.
• the projections are adapted so that the exerted capillary force is different for the different sinks and flow paths.
• an integrated analysis comprising three steps is performed.
• a specific example of such an analysis is a device according to Fig 1c, where a first antibody directed against the analyte is bound to the analysis point.
• the sample passes the analysis point and the analyte is bound to a fraction of the first antibodies on the surface.
• a second antibody directed against the analyte, which antibody comprises a general binding unit passes the analysis point.
• the second antibody will bind to the analyte which is bound to the first antibodies at the analysis point.
• a detectable molecule with the capability of binding to the general binding unit on the second antibodies passes the analysis point.
• the detectable molecules are bound to the antibodies.
• a method of analysing a sample wherein the analysis is performed using a device as described above.
• the sample is preferably added to the zone for receiving the sample.
• the method preferably comprises a step of reading a result of the analysis.
• kits of parts comprising the device as described above and at least one reagent.
• the kit of parts comprises a further assay device.
• an assay device include a holder for the device, a measurement apparatus where said device is inserted or another device which facilitates the analysis.
• such kit of parts comprises at least one package.
• the kit of parts comprises a written instruction.
• the kit of parts comprises a reader capable of performing a measurement on said device. Such a reader may make a measurement on the analysis point.
• Fig 2a Black rectangles symbolises a reactant in Fig 2.
• the liquid flows into the zone for receiving a sample.
• the sample flows over the analysis point where the measurement is performed. Due to the higher capillary force in one of the flow paths the liquid flows along the flow path with the highest capillary force and fills the sink with the higher capillary force. Not until the sink with the higher capillary force is completely filled, the liquid will start to flow into the region with the lower capillary force.
• the time and the volume of sample that passes the analysis point in the first step is defined by filling the sink with the higher capillary force.

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

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• 2007
  • 2007-04-16 SE SE0700930A patent/SE529978C2/sv unknown
• 2008
  • 2008-04-15 CN CN200880012452.4A patent/CN101678355B/zh active Active
  • 2008-04-15 CA CA2683920A patent/CA2683920C/en not_active Expired - Fee Related
  • 2008-04-15 WO PCT/SE2008/050424 patent/WO2008127191A1/en active Application Filing
  • 2008-04-15 JP JP2010504015A patent/JP5425757B2/ja active Active
  • 2008-04-15 EP EP08741914.9A patent/EP2134472A4/de not_active Ceased

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Non-Patent Citations (1)

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