JP5425757B2 - Apparatus for processing liquid samples - Google Patents

Description

Disclosure details

〔Technical field〕
The present invention relates to the field of devices for processing liquid samples.

〔background〕
Devices for processing various types of liquid samples are desirable for use, for example , in the field of medical procedures . Such devices can also be used to analyze a variety of samples including blood, plasma, serum, sweat, saliva, urine, tears, test water, and food sample suspensions or solutions. it can.

  Such assay devices are, for example, international publications WO 2005/118139 (AMIC AB), WO 2005/089082 (AMIC AB), and WO 03/103835 (Amic ( AMIC AB)).

  Other assay devices are described, for example, in US Pat. No. 5,458,852 (BIOSITE) and European Patent 1120164 (ROCHE DIAGNOSTICS GMBH).

  British Patent 2410086 (BRITISH BIOCELL INTERNAT LTD) discloses an assay device comprising a flow block for determining liquid flow.

  US Pat. No. 6,296,020 (BIOMICRO SYSTEMS, INC.) Discloses a method for controlling the flow of fluid through a microchannel by use of a passive valve or stop means.

[Disclosure of the Invention]
[Technical issues]
In some known assay devices, a sample containing an analyte is added and the sample flows along a flow path in which the dried reagent is dissolved. Samples reagent became including way, it flows until analysis point samples for one or more characteristics are analyzed. This type of technology has a number of problems.

  One problem with the above technique is how to get the sample to the analysis point before the reagent. It is desirable in some applications.

  Another problem is how to accurately and reproducibly define a specific amount of sample that passes through the analysis point before the reagent reaches the analysis point.

  Another problem is how to react the sample for a long time at the analysis point before the reagent reaches the analysis point.

Another problem is the reagent by the degree of drying of the life and reagents for example reagent is to remove the effect from the fact that otherwise dissolves (effects).

  The measured signal in an assay depends on the amount of reagent and the amount of sample. In many assays, certain particles and / or certain molecules are detected, so the amount of sample must be clearly defined.

[Technical solution]
One object of the present invention is to mitigate at least some of the problems in the state of the art.

  It is achieved by using the present invention which provides in a first aspect an apparatus for processing a liquid sample, the apparatus comprising: a) a protrusion substantially perpendicular to the surface of the apparatus, the height of which is A protrusion having a diameter and a distance between the protrusions and capable of generating a capillary flow of fluid laterally of the surface; b) at least one region for receiving a sample; c) Coupling at least one sink having the ability to receive liquid and exerting at least two different capillary forces on said liquid; and d) said at least one region for receiving sample and said at least one sink And at least two flow paths that exert at least two different capillary forces on the liquid, and e) at least one connection between the at least two flow paths.

  The assay device utilizes a protrusion that is substantially perpendicular to the surface to create a capillary force for fluid flow. The device takes advantage of the fact that the capillary force can be different for different flow channels, depending on the distance, form, diameter, and height of the protrusions. The difference in capillary force is used to direct the flow in the desired direction.

  Also included within the scope of the present invention are methods for analyzing samples and kits of parts.

[Benefit effect]
Advantages of the present invention include the ability to allow the sample to reach the analysis point before the reagent. Another advantage is that a specific amount of sample can pass through the analysis point before the reagent reaches the analysis point. Yet another advantage is that the effects of various dissolution of reagents can be removed or reduced.

[Definition]
Before describing and disclosing in detail the present invention, it will be appreciated that, for the specific structures, processing steps, and materials disclosed herein, such structures, processing steps, molecules, and materials may vary somewhat. It should be understood that it is not limited as it can vary. Also, the terminology used herein is used only to describe certain embodiments and is limited only as the scope of the invention is limited only by the appended claims and equivalents thereof. It should be understood that this is not the intention.

  As used herein and in the appended claims, the singular forms “a”, “an”, and “the” are clearly contextual. It should be noted that it includes a plurality of instructions unless otherwise indicated. The following terms are used throughout the specification and claims.

  “Analysis” is used herein to indicate the process by which a sample is tested to gain its understanding, for example, regarding its qualitative and / or quantitative composition.

  An “analysis point” is used herein to indicate the point or area of the assay device where the measurement is performed.

  “Analyte” is used herein to indicate the substance, chemical component, or biological component being analyzed.

  “Reagent” is used herein to indicate a chemical or biological component involved in an analysis.

  “Sample” is used herein to indicate anything that contains an analyte.

[Detailed explanation]
At least some of the above advantages are achieved by using an assay device of special design. The assay device utilizes protrusions that are substantially perpendicular to the surface to create a capillary force so that liquid can flow. The assay device takes advantage of the fact that the capillary force can be different for different flow channels, depending on the distance, form, diameter, and height of the protrusions. The difference in capillary force is used to direct the flow in the desired direction.

  In one embodiment shown in FIG. 1a, an apparatus for processing a liquid sample includes one region for sample reception, shown as a circular region. There are two independent rectangular sinks with the ability to receive liquid, two flow paths each connected to a single sink, and at least one connection between the two flow paths. . In this embodiment, the reactants are dried on the substrate in the area marked “k”. Furthermore, embodiments include a gate that allows liquid flow when contacting the liquid from at least two directions, as shown by “g” in FIG.

  It should be noted that such a gate only allows liquid flow when contacting the liquid from more than one side. An example of a gate that can be used in the present invention is shown in FIG. It should be noted that the gates that can be used in the present invention are not limited to the gates shown in FIG. Any type of gate can be used that prevents liquid flow when contacting liquid from only one side and allows liquid flow when contacting liquid from more than one side. .

  When liquid flows from left to right in the flow path shown in FIG. 4, the flow is blocked and when the liquid flows from right to left, the gate allows flow in both directions. The flow of liquid from right to left flows through a small channel on the side of the main channel, allowing the liquids to come together from both sides, thereby allowing them to flow over the gate. It is achieved when the capillary force of the gate is adapted to the liquid of interest by adjusting the position, distance, form, diameter, and height of the protrusion and the width and position of the small channel It is possible.

  In one embodiment, the gate includes a protrusion having an adjusted position, distance, form, diameter, and height.

  In another embodiment, there is no gate. Instead, the flow of at least one of the channels is made slower than the remaining channels by lengthening the channels and / or reducing the capillary force over the liquid.

  The distance, form, diameter, and height of the protrusion are configured such that at least a portion of the flow path and the capillary force of one of the sinks is higher than the flow path leading to the other sink. .

In one embodiment, at least one reagent is adsorbed on the surface of at least one of the channels. In another embodiment, the reagent is adsorbed in the channel that exerts the lowest capillary force.

  The flow paths that exert different capillary forces on the liquids, in one embodiment, have different flow rates for each liquid due to the different capillary forces.

  One embodiment of the flow path intersection of FIG. 2 is shown in FIG. 3 and consists of a specific embodiment of protrusions having different spaces to create different capillary forces.

  In one embodiment shown in FIG. 1a, there are two different sinks that exert different capillary forces on the liquid. In another embodiment shown in FIG. 1d, there is one sink divided into two parts that exerts different capillary forces on the liquid. The boundary between these parts is indicated by the dotted line in FIG. When the portion that exerts the highest capillary force is completely filled, the liquid begins to flow into the region that exerts a lower capillary force on the liquid, so that the action is the same as in FIGS. 1a and 1b.

In one embodiment, the object substance is adsorbed and / or bonded to the analysis points. In one embodiment, such substances have the property of binding to at least one analyte. Examples of such substances include antibodies.

In one embodiment, at least one reagent is adsorbed or dried on at least one flow channel. Such a reagent can be any chemical or biological entity that participates in the analysis. Examples of reagents include antibodies, antibodies that contain a detectable entity, other detectable molecules, and molecules that have the ability to bind to an analyte.

  In another embodiment, a multi-stage analysis can be performed, for example, where two, three, or more reagents are added sequentially with a time lag. Such an embodiment is shown in FIG. 1c, and two independent reagents k and k 'are added after each other. In one embodiment, at least three different capillary forces are exerted on the liquid, the first capillary force forms a first sink, the second capillary force forms a second sink, and a third capillary The force forms a third sink. In one embodiment, there are different sized sinks shown in FIG. 1c. In another embodiment, the protrusions are configured such that the applied capillary force is different for different sinks and channels.

In another embodiment, an analysis that includes two or more steps can be performed. In one embodiment, a combined analysis comprising three steps is performed. Specific examples of such an analysis, there is apparatus according to Fig. 1c, a first antibody against the analyte is coupled to the analysis points. In the first step, the sample passes through the analysis point and the analyte is bound to a portion of the first antibody on the surface. In the second step, a general coupling units (binding Unit) A including a second antibody, a second antibody against the analyte, passes through the analysis point. In the second step, the second antibody binds to an analyte that is bound to the first antibody at the analysis point. In the third step, detectable molecules that have the ability to bind the second antibody to the general binding unit pass through the analysis point. In the third step, the detectable molecule is bound to the antibody. The advantage of this three-step analysis is that the third step is the same for all types of inspection, which can be optimized at once for many different inspections.

  In a second aspect of the invention, a method for analyzing a sample is provided, and the analysis is performed using an apparatus as described above. In such a method, preferably the sample is added to an area for receiving the sample. Preferably, the method includes the step of reading the results of the analysis.

  In a third aspect of the present invention, a kit of parts comprising an apparatus as described above and at least one reagent is provided. Optionally, the component kit includes a separate assay device. Examples of such assay devices include a holder for the device, a measuring device into which the device is inserted, or other devices that facilitate analysis. In one embodiment, such a component kit includes at least one package. In other embodiments, the parts kit includes written instructions. In another embodiment, the component kit includes a reader that can perform measurements on the device. Such a reader can perform measurement at the analysis point.

In one embodiment, when a liquid sample is added to a region that receives the sample, the liquid flows to the gate of one flow path and the reagent is dissolved by the sample. It is shown in Fig. 2a. In FIG. 2, the black rectangle symbolizes the reactant. In the other channel, the liquid flows into the area for receiving the sample. The sample passes the analysis point where the measurement is performed. Due to the high capillary force of one channel of the flow path, the liquid flows along the flow path having the largest capillary force to fill the sink with a higher capillary force. Until sink having a higher capillary force is filled completely, the liquid does not begin to flow into the area with a lower capillary force. The amount and time of the sample through the analytical point in the first step is determined by filling the sink with a higher capillary force. In FIG. 2b, a sink having a higher capillary force is filled completely, and the sample begins to flow into the region on the lower capillary force on the liquid.

  The liquid then flows towards the gate, so that when both sides of the gate come into contact with the liquid, the liquid can flow across the gate in both directions. The liquid with dissolved reactants flows towards the other sink as shown in FIG. 2c. FIG. 2c shows that the dissolved reactant, symbolized by a black rectangle, passes through the analysis point. In FIG. 2d, the measurement is complete, all sinks are completely filled, and / or there is no more sample volume available. Thus, the time before the gate is opened can be well defined and the time is adjusted so that the reagent can be sufficiently dissolved.

FIG. 2 shows various embodiments of an apparatus according to the present invention. FIG. 2 shows various embodiments of an apparatus according to the present invention. FIG. 2 shows various embodiments of an apparatus according to the present invention. FIG. 2 shows various embodiments of an apparatus according to the present invention. FIG. 2 shows various stages during use of the device according to the invention. FIG. 2 shows various stages during use of the device according to the invention. FIG. 2 shows various stages during use of the device according to the invention. FIG. 2 shows various stages during use of the device according to the invention. FIG. 3 is an electron micrograph of a part of the analysis device according to the invention, showing for example the intersection of two flow channels as used in the device shown in FIG. It is a figure which shows the cross section of the flow channel containing the gate which can be used for the assay apparatus based on this invention.

Claims (13)

In an apparatus for processing a liquid sample,
a) a protrusion substantially perpendicular to the surface of the device, the protrusion having a height, a diameter and a distance between the protrusions and capable of generating a capillary flow of fluid laterally of the surface And
b) at least one region for receiving a liquid sample;
have the capability for receiving the c) i) said liquid, respectively capillary force becomes different have at least two portions on the liquid sample, at least one sink, and ii) different capillary forces, respectively One selected from at least two different sinks that affect the liquid sample ;
d) at least two flow paths connecting the at least one region for receiving a liquid sample and the at least one sink and exerting at least two different capillary forces on the liquid sample , the highest capillary force The flow path that is coupled to the sink or the portion that exerts the highest capillary force; and
e) at least one connection between the at least two flow paths;
Including the device. The apparatus of claim 1 .
An apparatus wherein at least one of the flow paths includes at least one gate that allows liquid sample flow when contacting the liquid from at least two directions. The apparatus of claim 2 .
The device, wherein the gate further comprises a protrusion substantially perpendicular to the surface of the device. The apparatus according to any one of claims 1 to 3
An apparatus in which at least one reagent is adsorbed in at least one of the flow paths. The device according to any one of claims 1 to 4 ,
An apparatus in which at least one reagent is adsorbed in the flow path that exerts the lowest capillary force on the liquid sample . In the apparatus of any one of Claims 1-5 ,
The apparatus, wherein the at least two flow paths have different flow rates with respect to the liquid sample . In the apparatus of any one of Claims 1-6 ,
The device exerts at least three different capillary forces on the liquid sample . The apparatus of claim 7 .
The apparatus further comprises at least two different reagents. In a method for analyzing a sample:
A device according to any one of claims 1 to 8 is used,
The method, wherein the liquid sample is added to the at least one region for receiving a liquid sample. The method of claim 9 , wherein
A method wherein a result is read from the device. In the kit of parts,
An apparatus according to any one of claims 1 to 8 ,
At least one reagent;
Including parts kit. The kit of parts according to claim 11 ,
Analysis equipment,
A kit of parts further comprising: In a kit of parts according to any one of claims 11-12,
At least one reading device capable of performing measurements on said device;
A kit of parts further comprising:

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