EP1916524A1 - Elément d'essai rotatif - Google Patents

Elément d'essai rotatif Download PDF

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Publication number
EP1916524A1
EP1916524A1 EP06020219A EP06020219A EP1916524A1 EP 1916524 A1 EP1916524 A1 EP 1916524A1 EP 06020219 A EP06020219 A EP 06020219A EP 06020219 A EP06020219 A EP 06020219A EP 1916524 A1 EP1916524 A1 EP 1916524A1
Authority
EP
European Patent Office
Prior art keywords
sample
test element
axis
zone
porous
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.)
Ceased
Application number
EP06020219A
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German (de)
English (en)
Inventor
Erfindernennung liegt noch nicht vor Die
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.)
F Hoffmann La Roche AG
Roche Diagnostics GmbH
Original Assignee
F Hoffmann La Roche AG
Roche Diagnostics GmbH
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 F Hoffmann La Roche AG, Roche Diagnostics GmbH filed Critical F Hoffmann La Roche AG
Priority to EP06020219A priority Critical patent/EP1916524A1/fr
Priority to CA2664565A priority patent/CA2664565C/fr
Priority to JP2009529607A priority patent/JP5502482B2/ja
Priority to ES19160587T priority patent/ES2933349T3/es
Priority to PCT/EP2007/008419 priority patent/WO2008037469A1/fr
Priority to EP07818502.2A priority patent/EP2069787B1/fr
Priority to CN2007800357229A priority patent/CN101517413B/zh
Priority to ES07818502T priority patent/ES2724734T3/es
Priority to EP19160587.2A priority patent/EP3524982B1/fr
Publication of EP1916524A1 publication Critical patent/EP1916524A1/fr
Priority to US12/407,419 priority patent/US8470588B2/en
Priority to HK10101882.7A priority patent/HK1136626A1/xx
Ceased legal-status Critical Current

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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
    • B01L3/502753—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 bulk separation arrangements on lab-on-a-chip devices, e.g. for filtration or centrifugation
    • 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
    • B01L3/5023—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures with a sample being transported to, and subsequently stored in an absorbent for analysis
    • 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
    • B01L2200/00—Solutions for specific problems relating to chemical or physical laboratory apparatus
    • B01L2200/06—Fluid handling related problems
    • B01L2200/0605—Metering of fluids
    • 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
    • B01L2300/06—Auxiliary integrated devices, integrated components
    • B01L2300/0681—Filter
    • 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
    • B01L2300/069—Absorbents; Gels to retain a fluid
    • 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
    • B01L2300/0803—Disc shape
    • B01L2300/0806—Standardised forms, e.g. compact disc [CD] format
    • 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
    • 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
    • B01L2400/04—Moving fluids with specific forces or mechanical means
    • B01L2400/0403—Moving fluids with specific forces or mechanical means specific forces
    • B01L2400/0409—Moving fluids with specific forces or mechanical means specific forces centrifugal 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
    • B01L2400/082—Active control of flow resistance, e.g. flow controllers
    • Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y10—TECHNICAL SUBJECTS COVERED BY FORMER USPC
    • Y10T—TECHNICAL SUBJECTS COVERED BY FORMER US CLASSIFICATION
    • Y10T436/00—Chemistry: analytical and immunological testing
    • Y10T436/11—Automated chemical analysis
    • Y10T436/110833—Utilizing a moving indicator strip or tape
    • Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y10—TECHNICAL SUBJECTS COVERED BY FORMER USPC
    • Y10T—TECHNICAL SUBJECTS COVERED BY FORMER US CLASSIFICATION
    • Y10T436/00—Chemistry: analytical and immunological testing
    • Y10T436/11—Automated chemical analysis
    • Y10T436/111666—Utilizing a centrifuge or compartmented rotor

Definitions

  • the invention relates to a test element, which is substantially disc-shaped and flat and about a central axis which is perpendicular to the disc-shaped test element plane, rotatable, comprising a sample application port for discharging a liquid sample, a porous, absorbent matrix and a sample channel, of the Sample introduction opening to the porous, absorbent matrix is sufficient. Furthermore, the invention relates to a method for determining an analyte with the aid of the test element.
  • test carriers eg. B. Test strips offered. Prominent examples of these are test strips for the determination of the blood glucose value or test strips for urinalysis.
  • test carriers usually integrate several functions (eg the storage of reagents in dried form or, albeit less frequently, in solution, the separation of undesired sample constituents, in particular of red blood cells from whole blood, in immunoassays, the so-called Free separation, the dosing of sample volumes, the transport of sample liquid from outside a device into a device, the control of the sequence of individual reaction steps, etc.).
  • the function of the sample transport is often accomplished by means of absorbent materials (eg papers or fleeces), by means of capillary channels or by application of external driving forces (such as pressure, suction) or by means of centrifugal force.
  • Disc-shaped test carriers so-called LabDiscs or optical BioDiscs, continue the idea of controlled sample transport by means of centrifugal force (centrifugal force).
  • Such Disc-shaped, CompactDisc-like test carriers allow miniaturization through the use of microfluidic structures and at the same time the parallelization of processes by repeated application of identical structures for the parallel processing of similar analyzes from a sample or identical analyzes from different samples.
  • optical BioDiscs the integration of optically stored digital data for the identification of the test carriers or the control of the analysis systems on the optical BioDiscs is possible.
  • BioDiscs In addition to the miniaturization and parallelization of analyzes and the integration of digital data on optical discs, BioDiscs generally have the advantage that they can be manufactured using established manufacturing methods and measured using established evaluation technology. In the chemical and biochemical components of such optical BioDiscs usually a recourse to known chemical and biochemical components is possible.
  • a disadvantage of the optical LabDiscs or Biodiscs based purely on centrifugal and capillary forces is that the immobilization of reagents is difficult and the accuracy of detection suffers. Especially in detection systems based on specific binding reactions, such.
  • As immunoassays lacks compared to conventional test strip systems, the volume component, especially in the so-called. Bound-Free separation.
  • BioDiscs with channels and channel-like structures for liquid transport on the one hand and voluminous absorbent materials in these structures (at least partially) on the other.
  • WO 2005/001429 (Phan et al. ) describes optical bio-discs which have membrane pieces as reagent carriers in parts of the channel system. The reagents are dissolved by a liquid supplied to the disc, resulting in buffered reagent solutions, which are then contacted with the sample.
  • optical bio-disks which contain absorbent membranes or papers for moving a sample liquid, separating particulate sample components, carrying reagents, and analyzing the sample.
  • the sample is first applied to a blood separation membrane near the outer edge of the bio-disk and migrates radially therethrough to a reagent paper located closer to the center of the bio-disk. Thereafter, the sample is again moved radially outward, ie away from the center of the bio-disk, and flows through a so-called Analysis membrane.
  • the outward movement takes place via chromatography, which is supported by rotation of the bio-disk and the centrifugal force acting thereon on the sample.
  • US 2002/0076354 A1 discloses bio-optical discs having, in addition to a channel system for the transport of a liquid sample, a so-called “capture layer".
  • the latter can for example consist of nitrocellulose.
  • the "interception layer” is traversed by means of centrifugal forces during rotation of the disk.
  • a disadvantage of the concepts of the prior art is that just for specific binding assays, such.
  • immunoassays targeted control of the reaction and residence times of the sample liquid after receiving the reagents and after flowing into the porous, absorbent matrix is not possible.
  • the object of the invention is to eliminate the disadvantages of the prior art.
  • the invention relates to a test element according to claim 1 or 14, a measuring system according to claim 18, the use thereof according to claim 19, as well as a method according to claim 15.
  • Advantageous embodiments and preferred embodiments of the invention are the subject of the dependent claims.
  • test element is essentially disc-shaped and planar. It is rotatable about a central axis which is perpendicular to the disk-shaped test element plane.
  • the test element is a circular disc, comparable to a compact disc.
  • the invention is not limited to this form of the disc, but can readily be found in non-symmetrical or non-circular discs use.
  • the test element first contains a sample introduction opening into which a liquid sample can be pipetted or introduced in another way.
  • the Sample loading aperture can either be close to the axis (ie near the center of the disc) or far away from the axis (ie near the edge of the disc).
  • the test element contains at least one channel, which can transfer the liquid sample from the off-axis position into an axis-near position by means of capillary forces.
  • the sample application opening can open directly into a sample channel.
  • the sample introduction opening can first open into a reservoir located behind it, into which the sample flows before it continues to flow into the sample channel.
  • a hydrophilization of the surfaces of the fluidic structures may be necessary and / or the use of structures that promote the formation of capillary forces.
  • test element contains a porous, absorbent matrix which accommodates at least part of the liquid sample.
  • the matrix has an off-axis first end and an off-axis second end.
  • the test element also has a sample channel that extends from the sample introduction port to the off-axis first end of the porous absorbent matrix. At least once, the sample channel passes through an area close to the axis, which is closer to the central axis than the first end of the porous matrix, which is remote from the axis.
  • the porous, absorbent matrix has an axis-proximate second end.
  • the off-axis first end of the porous, absorbent matrix is in contact with the sample channel, in which the sample can be moved by capillary forces and / or centrifugal forces and / or other external forces, such as overpressure or underpressure.
  • the liquid sample - possibly after taking up reagents and / or dilution media and / or precluding reactions - reaches the off-axis first end of the porous, absorbent matrix, it is taken up in the matrix and transported through the suction forces.
  • the porous, absorbent matrix is a paper, membrane or web.
  • the porous absorbent matrix typically contains one or more zones of immobilized reagents.
  • specific binding agents such as specific binding partners, such as antigens, antibodies, (poly) haptens, streptavidin, polystreptavidin, and the like, are immobilized in the absorbent matrix. They serve to selectively capture from the sample flowing through the absorbent matrix the analyte or analyte-derived and related species.
  • an antibody to the analyte may be immobilized in the porous, bibulous matrix which will then capture the analyte (in this case, an antigen or hapten) from the sample and also immobilize it in the bibulous matrix.
  • the analyte can be made detectable by further reactions, for example by further contacting with a labeled bindable partner, for example by a label which can be visually, optically or fluorescently detected.
  • the porous, absorbent matrix with the second end close to the axis adjoins another absorbent material, so that this liquid can absorb from the matrix.
  • the matrix and other material overlap slightly for this purpose.
  • the other material serves on the one hand to support the suction of the matrix, on the other hand as a receiving zone for liquid, which has already passed through the matrix.
  • the further material may consist of the same or different materials, such as the matrix.
  • the matrix may be a membrane and the other absorbent material may be a nonwoven or a paper. Other combinations are of course possible as well.
  • the test element according to the invention is characterized in a preferred embodiment in that the sample channel contains zones of different dimensions and / or for different functions.
  • the sample channel may contain a zone containing soluble or suspendible reagents in the sample. These can be dissolved or suspended in the liquid sample when it flows in or through it and can react with the analyte in the sample or with other sample components.
  • the different zones in the sample channel may also differ in that there are zones with capillary activity and those without.
  • zones of high hydrophilicity and low hydrophilicity may be included.
  • the individual zones can virtually seamlessly pass into each other or through certain barriers, such as valves, in particular non-closing valves, such as geometric valves or hydrophobes be separated from each other.
  • the reagents in the sample channel are preferably in dried or lyophilized form. However, it is also conceivable, although less preferred, for reagents to be present in liquid form in the test element according to the invention.
  • the reagents can be introduced into the test element in a manner known per se.
  • the test element preferably contains at least two layers, a bottom layer into which the fluidic structures are introduced, and a cover layer, which as a rule contains no further structures apart from the inlet openings for liquids and the vent openings.
  • the introduction of reagents during the preparation of the test device is usually carried out before the upper part of the test element (cover layer) is applied to the lower part (bottom layer). At this time, the fluidic structures are open in the lower part, so that a dosage of the reagents in liquid or dried form is readily possible.
  • the introduction of the reagents can be done for example by printing or dispensing.
  • the reagents into the test element by placing them in the test element impregnated in absorbent materials such as papers, nonwovens or membranes. After placing the reagents and inserting the absorbent materials, such as the porous, absorbent matrix (membrane) and optionally other absorbent materials (non-woven waste etc.) upper and lower part of the test element are connected to each other, for example, clipped, welded, glued and such more.
  • absorbent materials such as papers, nonwovens or membranes.
  • the bottom layer in addition to the fluidic structures also has the inlet openings for liquids and the vent openings.
  • the cover layer may be formed completely without openings, with the possible exception of a central recess for receiving a drive unit.
  • the upper part simply consist of a plastic film which is glued or welded to the lower part.
  • the sample channel contains a zone for separating particulate matter from the liquid sample.
  • this zone serves to separate the cellular sample components. From blood can be so by separating in particular the red blood cells (erythrocytes) almost colorless plasma or serum which is usually better suited for subsequent visual or optical detection methods than the strongly colored blood.
  • the separation of cellular sample components by centrifugation, d. H. by fast rotation of the test element after filling with liquid sample contains suitably dimensioned and geometrically designed channels and / or chambers for this purpose.
  • the test element for the separation of cellular blood components contains an erythrocyte collection zone (erythrocyte chamber or erythrocyte trap) and a serum or plasma collection zone (serum or plasma chamber).
  • valves In control the flow of the sample liquid in the test element, it may contain valves, in particular so-called non-closing or geometric valves or hydrophobic barriers, especially in the sample channel.
  • valves or hydrophobic barriers can be used to ensure that a targeted temporal and spatial control of the sample flow through the sample channel and the individual zone of the test element is possible.
  • the sample channel may have a sample metering zone, which allows a precise measurement of the - initially in excess abandoned - sample.
  • the sample metering zone extends from the sample application opening via a corresponding piece of a sample channel to a valve in the fluidic structure, in particular a geometric valve or a hydrophobic barrier.
  • the sample application opening can initially receive an excess of sample material.
  • the sample either driven by capillary forces or by centrifugation, flows from the sample application zone into the channel structure and fills it up to the valve. Excess sample initially remains in the sample application zone.
  • a sample excess chamber adjacent to the sample application zone and branching off from the sample channel is filled, for example by capillary forces or by centrifuging the test element. It must be ensured that the sample volume to be measured is initially not transported across the valve by suitably selecting the valve. As soon as excess sample is trapped in the appropriate transfer chamber, there is a well-defined sample volume between the valve of the sample channel on one side and the entrance to the sample overflow chamber on the other side. By applying external forces, in particular by starting another centrifugation, this defined sample volume now extends beyond the valve emotional. All fluidic areas that lie after the valve and come into contact with the sample are now filled with a precisely defined sample volume.
  • the sample channel may also have an inflow for other liquids except the sample liquid.
  • a second channel open, the z. B. can be filled with a washing or reagent liquid.
  • the inventive system of measuring device and test element is used to determine an analyte in a liquid sample.
  • the measuring device contains at least one drive for the rotation of the test element and an evaluation optics for evaluating the visual or optical signal of the test element.
  • the optics of the measuring device can be used for fluorescence measurement with spatially resolved detection.
  • d. H. planar evaluation optics is typically used to illuminate the detection area of the test element and possibly the excitation of optically detectable markers an LED or a laser.
  • the detection of the optical signal is by CMOS or CCD (typically 640 x 480 pixels).
  • the beam path is direct or folded (eg via mirrors or prisms).
  • the illumination or excitation is typically effected by means of an illumination line which illuminates the detection area of the test element, preferably perpendicular to the detection and control lines.
  • the detection can be done here via a diode array.
  • the rotational movement of the device can be utilized for the illumination and evaluation of the second dimension in order to scan with the diode array over the area of the test element to be evaluated.
  • a DC motor with encoder or a stepper motor can be used as drive for rotating and positioning of the test element.
  • the temperature of the test element in the device is made indirectly, for example by heating or cooling the plate on which rests the disc-shaped test element in the device.
  • the measurement of the temperature is preferably carried out without contact.
  • the method according to the invention serves to detect an analyte in a liquid sample.
  • the sample is first introduced into the sample application opening of the test element according to the invention.
  • the test element is rotated about its central axis: The sample is transported from the sample application opening to the off-axis end of the porous, absorbent matrix.
  • the rotation of the test element then becomes so far slows or stops that the sample or a material obtained from the sample as it flows through the test element from the off-axis to the near-axis end of the porous, absorbent matrix is sucked.
  • the analyte is finally visually or optically detected in the porous, absorbent matrix or a downstream zone.
  • the detection can be carried out according to the principle of the sandwich assay or in the form of a competitive assay.
  • the further liquid may in particular be a buffer, preferably a washing buffer, or a reagent liquid.
  • the porous, absorbent matrix transports the liquid from an off-axis end to an off-axis end, i. H. from the periphery of the disk-shaped test element in the direction of the axis of rotation.
  • the centrifugal force which can also be used to move the liquids, counteracts this direction of transport exactly.
  • Targeted control of the rotation of the test element therefore makes it possible to slow down or stop the flow of the sample liquid in the porous, absorbent matrix, so that targeted and defined reaction conditions can be maintained.
  • the use of the porous absorbent matrix which serves essentially as a scavenger matrix for bound-free separation in immunoassays, allows efficient capture of sample components during the immunoassay.
  • FIG. 1 shows a schematic representation of a plan view of a preferred embodiment of the test element according to the invention. For the sake of clarity, only the layer of the test element which contains the fluidic structures is shown. The embodiment shown here contains only one opening for introducing sample and / or washing liquid. The separation of interfering sample components is done in this embodiment) after the sample has been contacted with reagents.
  • FIG. 2 schematically shows a further preferred embodiment of the test element according to the invention. Again, only the structure has been shown, which has the fluidic elements of the test element. In this embodiment of the test element there are two separate sample and wash buffer application ports. A separation of the cellular sample components takes place here already before the sample is brought into contact with reagents.
  • FIG. 3 shows a variant of the embodiment according to FIG. 1 in a schematic representation. Again, the separation of cellular sample components, after which the sample was brought into contact with reagents. However, the structure according to FIG. 3 has a separate feed for washing liquid.
  • FIG. 4 shows a further preferred embodiment of the test element according to the invention in a schematic view analogous to FIG. 2.
  • FIG. 5 represents a slight further development of the test element according to FIG. 3.
  • FIG. 5 contains a different geometric arrangement of the waste nonwoven and another type of valve at the end of the sample metering section.
  • FIG. 6 schematically shows a plan view of a further development of the test element according to FIG. 5.
  • the embodiment according to FIG. 6 contains a fluidic structure for receiving a sample excess.
  • FIG. 7 is a schematic representation of a further variant of the test element according to FIG. 3. Functionally, the fluidic structures are essentially analogous to those of FIG. 3. However, they are geometrically differently aligned and designed.
  • FIG. 8 schematically shows a further preferred embodiment of the test element according to the invention.
  • the structures in FIG. 8 essentially correspond to the functions which are already known by the test element according to FIG.
  • FIG. 9 schematically shows a plan view of an alternative to the test element according to FIG. 6.
  • the embodiment according to FIG. 9 contains an off-axis sample application opening, which initially brings the sample nearer to the center of the test element via a capillary, that is to say in FIG an off-axis area.
  • FIG. 10 shows the typical curve for troponin T measurements in whole blood samples (concentration of troponin T in ng / ml plotted against the signal strength (counts)). The samples were supplemented with recombinant troponin T to the respective concentration. The data belong to Example 2 and were obtained with the aid of test elements according to FIG. 6 / Example 1.
  • FIGS. 1 to 9 show different preferred embodiments of the test element (1) according to the invention.
  • each of the substrate (2) containing the fluidic structures and the central recess (drive hole 3) is shown.
  • the disk-shaped test element (1) according to the invention also generally comprises a cover layer, which in the figures provides clarity is not shown half.
  • the cover layer can also carry structures, but as a rule it will have no structures other than the openings for the samples and / or further liquids to be dispensed onto the test element.
  • the cover layer can also be designed completely without openings, for example in the form of a film, which is connected to the substrate and terminates the structures located therein.
  • FIGS. 1 to 9 show fluidic structures that perform largely similar functions, although they differ in detail from embodiment to embodiment.
  • the basic structure and the basic function will therefore be explained in more detail here with reference to the embodiment according to FIG.
  • the embodiments according to FIGS. 2 to 9 will subsequently be explained in more detail merely with reference to the specific differences in order to avoid unnecessary repetitions.
  • FIG. 1 shows a first preferred embodiment of the disk-shaped test element (1) according to the invention.
  • the test element (1) contains a substrate (2) containing the fluidic and microfluidic and chromatographic structures.
  • the substrate (2) is covered by a corresponding counterpart (cover layer) (not shown), which contains sample application and ventilation openings which lead to the structures in the substrate (2). correspond.
  • Both the cover layer and the substrate (2) have a central recess (3) which, in cooperation with a corresponding drive unit in a measuring device, makes it possible to rotate the disk-shaped test element (1).
  • the test element accordinging to one of FIGS.
  • Sample liquid in particular whole blood, is supplied to the test element (1) via the sample application opening (4). Driven by capillary forces and / or centrifugal forces, the sample liquid fills the sample dosing zone (5).
  • the sample metering zone (5) can also contain the dried reagents. It is limited by the Kapillarstopps (6 and 8), which may be formed for example as a hydrophobic barrier or as a geometric / non-closing valve.
  • the limitation of the sample dosing zone (5) by the capillary stops (6, 8) ensures that a defined sample volume is taken up and passed on into the fluidic zones which lie downstream of the sample dosing zone (5).
  • channel (9) is used to start the separation of red blood cells and other cellular sample components.
  • the reagents contained in the sample dosing zone (5) are already dissolved in the sample when the sample enters the channel (9).
  • the entry of the sample in channel (9) via the capillary stop (8) leads to a mixing of the reagents in the sample.
  • the reagent-sample mixture is directed into the fluidic structures (10) (serum / plasma collection zone) and (11) (erythrocyte collection zone). Due to the centrifugal forces acting on the reagent-sample mixture, plasma or serum is separated from red blood cells. The red blood cells collect in the process Erythrocyte collection zone (11) while the plasma remains substantially in the collection zone (10).
  • the membranes or nonwovens for separating particulate sample components use (for example, glass fiber webs or asymmetrically porous plastic membranes for separating red blood cells from whole blood) generally referred to as blood-separating membranes or nonwovens), the sample volume can be exploited much more effectively with the test elements according to the invention, as there are virtually no dead volumes (eg, volume of fiber interstices or pores) from which the sample can not be withdrawn.
  • these prior art blood separation membranes and webs tend in part to undesirably adsorb sample components (e.g., proteins) or destroy (lysate) cells, which is also not observed with the test elements of the present invention.
  • the reagent-plasma mixture (which has formed in the presence of the analyte in the case of an immunoassay, for example sandwich complexes of analyte and antibody conjugates) by the suction of the porous-absorbent matrix (12) incorporated into and passed through them.
  • the immobilized binding partners contained in the membrane (12) capture the analyte-containing complexes in the detection zone and bound unbound labeled conjugate in the control zone.
  • the nonwoven (13) adjoining the porous, absorbent matrix supports the movement of the sample through the membrane (12).
  • the fleece (13) also serves to receive the sample after flowing through the membrane (12).
  • wash buffer is pipetted into the sample application opening (4).
  • the washing buffer flows through the corresponding fluidic structures of the test element (1) and, in particular, washes the membrane (12), where the bound analyte complexes are now located, thus removing excess reagent residues.
  • the washing step may be repeated one or more times so as to improve the signal-to-background ratio. This allows an optimization of the detection limit for the analyte and an increase of the dynamic measuring range.
  • the sample channel in which the liquid sample in the test element (1) is transported from the sample application opening (4) to the first end of the membrane (12) remote from the axis comprises In this case, the sample dosing zone (5), the capillary stop (8), the channel (9), the serum / plasma collection zone (10) and the erythrocyte chamber (11). In other embodiments, the sample channel may consist of more or fewer individual zones / chambers.
  • FIGS. 3, 5, 6, 7 and 9 show essentially analogous embodiments to FIG. 1.
  • FIG. 3 differs from FIG. 1 in that on the one hand, no container for excess sample (7) adjoins the sample application opening (4) and at the end of the Probenendosierabitess (5) no capillary stop is present (ie here a metered sample application is required) and on the other hand, that a separate addition port (16) for other liquids, such as.
  • washing buffer, and an associated channel (15) are present, which can transport the buffer to the membrane (12).
  • the transport of the buffer to the membrane (12) can be based on capillary forces or centrifugal forces.
  • the embodiment according to FIG. 5 is largely identical to the embodiment according to FIG. 3.
  • the two embodiments differ only in the shape of the waste fleece (13) and in that the test element according to FIG. 5 has a capillary stop (8) at the end of the sample-metering section (FIG. 5).
  • FIG. 6 is again essentially identical to the embodiment according to FIG. 5 and differs therefrom by the additional presence of a container for sample excess (7) in the region between the sample metering opening (4) and the sample metering zone (5).
  • a container for sample excess (7) in the region between the sample metering opening (4) and the sample metering zone (5).
  • no metered application of the sample is required (analogous to FIG. 1).
  • the embodiment of the test element (1) according to the invention according to FIG. 7 substantially corresponds to the test element (1) of FIG. 6. Both embodiments have the same fluidic structures and functions. Only the arrangement and geometric design is different.
  • the embodiment according to FIG. 7 has additional ventilation openings (17), which are necessary due to the different dimensioning of the fluidic structures in comparison to FIG. 6 in order to allow filling of the structures with samples or washing liquid.
  • Channel (9) is designed here as a thin capillary, which is filled only during rotation of the test element (ie overcoming the capillary stop (8) is possible only by means of centrifugal force).
  • the test element (1) according to FIG. 7 it is possible with the test element (1) according to FIG. 7 to remove recovered plasma from the erythrocyte collection zone 11; This is done by the decanter unit 18, which finally discharges into the serum / plasma collection zone 10.
  • test element (1) according to the invention according to FIG. 9 essentially corresponds to the test element (1) of FIG. 6. Both embodiments have the same fluidic structures and functions. Only the arrangement and geometric design is different.
  • the embodiment according to FIG. 9 basically has a further outward, that is, away from the axis, sample application opening (4). This can be advantageous if the test element (1) for filling with sample is already introduced in a measuring device. In this case, the user can be made more easily accessible to the sample application opening (4) than is possible with test elements according to Figures 1 to 8, where the sample application opening (4) is arranged close to the axis (ie remote from the outer edge of the test element).
  • the separation of the cellular sample components from the sample liquid takes place before the sample comes into contact with reagents.
  • This has the advantage that the use of whole blood or plasma or serum as a sample material does not lead to different measurement results, since always initially plasma or serum comes into contact with the reagents and the dissolution / incubation / reaction behavior should be practically the same .
  • the liquid sample is first applied to the test element (1) via the sample application opening (4). By capillary forces and / or centrifugal forces, the sample is then transported from the sample application opening (4) in the channel structures.
  • the sample is transferred into a sample metering section (5) after it has been introduced into the sample application opening (4), and then a serum / plasma separation from the whole blood is effected by rotation.
  • the unwanted cellular sample constituents essentially erythrocytes, accumulate in the erythrocyte trap (11), while serum or plasma accumulate in the zone (10).
  • the serum is removed from the zone (10) via a capillary and transported further into the channel structure (9), where dried reagents are accommodated and are dissolved when the sample flows in.
  • the sample-reagent mixture of channel structure (9) can overcome the capillary stop (14) and thus reach the membrane (12) via the channel (15).
  • the sample-reagent mixture is transported via the membrane (12) into the waste nonwoven (13).
  • FIG. 2 and FIG. 4 differ from one another in that a container for sample excess (7) is provided in FIG. 2, while the embodiment according to Figure 4 does not provide such a function.
  • a metered application of the sample is expedient here.
  • FIG. 8 shows a variant of the embodiments according to FIGS. 2 and 4.
  • the sample is transferred by centrifugation into an erythrocyte separation structure (10, 11).
  • the area denoted by (10) serves as a serum / plasma collection zone (10) from which serum or plasma freed from cells is passed on via a capillary channel (21) after centrifuging.
  • Chamber (20) serves as a collecting reservoir for excess serum or plasma, which after complete filling of the sample dosing section (5) possibly flows from the serum / plasma collection zone (10). All other functions and structures are analogous to FIGS. 1 to 7.
  • the hydrophilic or hydrophobic properties of the surfaces of the test element (1) By deliberately designing the hydrophilic or hydrophobic properties of the surfaces of the test element (1), it can be achieved that the sample liquid and / or washing liquids are moved either only with the aid of rotation and the resulting centrifugal forces or by a combination of centrifugal forces and capillary forces. The latter requires at least partially hydrophilized surfaces in the fluidic structures of the test element (1).
  • test elements according to the invention according to FIGS. 1, 2, 6, 7, 8 and 9 have an automatic functionality which allows a relatively accurate measurement of a sample aliquot from a sample which has been applied in excess to the test element allowed (so-called "metering system").
  • This metering system is a further subject of the present invention. It essentially comprises the elements 4, 5, 6, and 7 of the illustrated test elements (1).
  • Sample liquid in particular whole blood, is supplied to the test element (1) via the sample application opening (4). Driven by capillary forces and / or centrifugal forces, the sample liquid fills the sample dosing zone (5).
  • the sample metering zone (5) can also contain the dried reagents.
  • the Kapillarstopps (6 and 8) which may be formed for example as a hydrophobic barrier or as geometric / non-closing valves.
  • the limitation of the sample dosing zone (5) by the capillary stops (6, 8) ensures that a defined sample volume is taken up and passed on into the fluidic zones which lie downstream of the sample dosing zone (5).
  • a possible excess sample from the sample application opening (4) and the sample dosing (5) is transferred to the sample surplus container (7) while the measured amount of sample is transferred from the sample dosing zone (5) to the channel (9).
  • sample liquid can be applied in excess to a test element.
  • the measurement of a relatively accurate sample aliquot, which is then further processed in the test element also takes place here by the interaction of a metering chamber and an overflow chamber, these two zones - unlike the present invention - by a narrow, but at least during filling always liquid exchange enabling contact.
  • Sample liquid is here directly separated during filling of the test element in a part which is passed through a wide channel in the "metering chamber", and a part which flows through a narrow channel in the "overflow chamber”.
  • the test element is set in rotation and any excess sample is diverted into the "overflow chamber” so that only the desired, measured sample volume remains in the "metering chamber", which is subsequently processed further.
  • a disadvantage of the embodiment of the metering system according to US 5,061,381 is that for sample volumes that are placed on the test element and which correspond exactly to the minimum volume or only slightly larger than the minimum volume, there is a risk that the dosing is underdosed, since always a portion of the sample from the beginning unhindered in the "overflow chamber" flows.
  • a capillary stop hydrophobic barrier or a geometric or non-closing valve
  • the capillary stop prevents sample from entering the sample excess zone before the sample dosing zone is completely filled. Also for sample volumes that are applied to the test element and which correspond exactly to the minimum volume or are only slightly larger than the minimum volume, it is ensured that the sample dosing zone is completely filled.
  • a substrate (2) according to FIG. 6 is produced from polycarbonate (PC) (alternatively polystyrene (PS), ABS plastic or polymethyl methacrylate (PMMA) is also possible as material) (dimensions approx. 60 ⁇ 80 mm 2 ).
  • a transition from shallower to deeper structures is usually only possible for liquids in the fluidic structures, if external force (eg centrifugal force) acts on them.
  • Such transitions act as geometric (non-closing) valves.
  • the substrate (2) also has the sample and buffer addition openings (4, 16), ventilation openings (17) and the central recess (3).
  • the surface of the substrate (2), which has the fluidic structures, can then be cleaned by means of plasma treatment and hydrophilized.
  • reagents required for analyte detection eg biotinylated anti-analyte antibodies and anti-analyte antibodies labeled with a fluorescence label
  • sample dosing section (5) eg biotinylated anti-analyte antibodies and anti-analyte antibodies labeled with a fluorescence label
  • the reagent solutions are composed as follows: Biotinylated antibody: 50 mM Mes pH 5.6; 100 ⁇ g / ml biotinylated monoclonal anti-troponin T antibody Labeled antibodies 50 mM Hepes pH 7.4, with squaric acid derivative Fluorescent dye JG9 (embedded in polystyrene latex particles) fluorescently labeled monoclonal anti-troponin T antibodies (0.35 percent solution)
  • porous matrix (12) nitrocellulose membrane on plastic carrier film, 21x5 mm 2 , reinforced with 100 micron PE film cellulose nitrate membrane (type CN 140 Sartorius, Germany)
  • an analyte detection line polystreptavidin
  • a control line polyhapten
  • aqueous streptavidin solution (4.75 mg / ml) is applied by line dosing to the above-described cellulose nitrate membrane.
  • the dosage is selected (dosage 0.12 ml / min, web speed 3 m / min), that a line with a width of about 0.4 mm is formed. This line is used to detect the analyte to be determined and contains about 0.95 ⁇ g streptavidin per membrane.
  • an aqueous troponin T polyhapten solution of 0.3 mg / ml is applied under identical dosing conditions. This line serves as a functional check of the test element and contains approx. 0.06 ⁇ g polyhapten per test.
  • the cover (film or injection molded part without Fluidik Modellen, which may or may be hydrophilized) is applied and optionally permanently connected to the substrate (2), preferably glued, welded or clipped.
  • the substrate is turned and in the corresponding recess the waste nonwoven fabric (13) (13 x 7 x 1.5 mm 3 fleece 100 parts of glass fiber (diameter 0.49 to 0.58 microns, length 1000 microns) and 5 Divide polyvinyl alcohol fibers (Kuralon VPB 105-2 from Kuraray) with a basis weight of about 180 g / m 2 ), which is then fixed by means of an adhesive tape in the substrate (2).
  • the waste nonwoven fabric 13 x 7 x 1.5 mm 3 fleece 100 parts of glass fiber (diameter 0.49 to 0.58 microns, length 1000 microns) and 5 Divide polyvinyl alcohol fibers (Kuralon VPB 105-2 from Kuraray) with a basis weight of about 180 g / m 2 ), which is then fixed by means of an adhesive tape in the substrate (2).
  • the quasi self-dosing sample receiving unit (comprising the sample application opening (4), the sample dosing (5) and the structures limiting it (capillary stop (8) and container for excess sample (7)) ensures that regardless of the on the test element (1) discontinued Amount of sample (if it exceeds a minimum volume (in this example 27 ⁇ l)) if different test elements are used, reproducibly the same amount of samples.
  • the reagents in the entire sample metering section (5) preferably in the form of alternating reagent spots (ie smaller, almost punctiform reagent areas), in combination with a rapid filling of the sample metering section (5) with sample, a homogeneous dissolution of the reagents in the entire sample volume is achieved , Especially if the filling is much faster than the release.
  • a virtually complete dissolution of the reagents so that here again an increased reproducibility compared to conventional, based on absorbent materials test elements (test strips, bio-discs with reagent pads, etc.) is observed.
  • test element On the test element according to Example 1, 27 .mu.l of whole blood to which different amounts of recombinant troponin T were added, abandoned. The test element is then further treated on the basis of the procedure given in Table 1 and finally measured the fluorescence signals for different concentrations.
  • Table 1 Measurement procedure Time (min: sec) Duration (min: sec) Rotation at revolutions per minute action 00:00 01:00 0 Add 27 ⁇ l sample; Dissolve the reagents 01:00 02:00 5000 Erythrocyte separation and incubation 03:00 01:00 800 Chromatography (generate signal) 04:00 12:10 0 Add 12 ⁇ l washing buffer 1 ) 04:10 02:00 800 Wash buffer transport and chromatography 06:10 12:10 0 Add 12 ⁇ l washing buffer 1 ) 06:20 02:00 800 Wash buffer transport and chromatography 08:20 12:10 0 Add 12 ⁇ l washing buffer 1 ) 08:30 02:00 800 Wash buffer transport and chromatography 10:30 0 measure up 1) 100 mM Hepes, pH 8.0; 150 mM NaCl; 0.095% sodium azide.
  • the measured data are shown in FIG.
  • the respective measurement signals (in counts) are plotted against the concentration of recombinant troponin T (c (TnT)) in [ng / ml].
  • the actual troponin T concentration in the whole blood samples was determined using the reference method "Roche Diagnostics Elecsys Troponin T Test".
  • the detection limit for the quantitatively evaluable measuring range with the test element according to the invention is shifted downwards (Cardiac Troponin T: 0.1 ng / ml, invention: 0.02 ng / ml) and the dynamic measuring range after dilated at the top (Cardiac Troponin T: 2.0 ng / ml, invention: 20 ng / ml).
  • the test elements according to the invention show improved precision.
EP06020219A 2006-09-27 2006-09-27 Elément d'essai rotatif Ceased EP1916524A1 (fr)

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EP06020219A EP1916524A1 (fr) 2006-09-27 2006-09-27 Elément d'essai rotatif
EP07818502.2A EP2069787B1 (fr) 2006-09-27 2007-09-27 Elément d'essai rotatif
JP2009529607A JP5502482B2 (ja) 2006-09-27 2007-09-27 回転可能試験素子
ES19160587T ES2933349T3 (es) 2006-09-27 2007-09-27 Elemento de prueba rotativo
PCT/EP2007/008419 WO2008037469A1 (fr) 2006-09-27 2007-09-27 Élément d'essai rotatif
CA2664565A CA2664565C (fr) 2006-09-27 2007-09-27 Element d'essai rotatif
CN2007800357229A CN101517413B (zh) 2006-09-27 2007-09-27 可旋转的测试元件
ES07818502T ES2724734T3 (es) 2006-09-27 2007-09-27 Elemento de prueba rotativo
EP19160587.2A EP3524982B1 (fr) 2006-09-27 2007-09-27 Élément d'essai rotatif
US12/407,419 US8470588B2 (en) 2006-09-27 2009-03-19 Rotatable test element
HK10101882.7A HK1136626A1 (en) 2006-09-27 2010-02-23 Rotatable test element

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Cited By (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP2145682A1 (fr) * 2008-07-18 2010-01-20 Roche Diagnostics GmbH Elément de test destiné à l'analyse d'un analyte contenu dans un échantillon de liquide corporel, système d'analyse et procédé de commande du mouvement d'un liquide contenu dans un canal d'un élément de test
EP2198964A1 (fr) 2008-11-06 2010-06-23 F. Hoffmann-Roche AG Procédé destiné à la préparation d'un réactif séché dans un système microfluidique et système microfluidique
WO2011027147A1 (fr) * 2009-09-03 2011-03-10 Vivacta Ltd Dispositif de prélèvement d'échantillons de fluide
WO2011120819A1 (fr) 2010-03-31 2011-10-06 Roche Diagnostics Gmbh Élément microfluidique comprenant une chambre de mesure multifonctionnelle
CN102239410A (zh) * 2008-12-03 2011-11-09 霍夫曼-拉罗奇有限公司 具有合并的对照和校准区的测试元件
EP2777499A1 (fr) * 2013-03-15 2014-09-17 Ortho-Clinical Diagnostics Inc Dispositif de collecte d'échantillon de fluide rotatif
EP3474019A4 (fr) * 2016-06-21 2020-05-06 UNIST (Ulsan National Institute of Science and Technology) Dispositif microfluidique

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* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US8632243B2 (en) * 2008-03-10 2014-01-21 The Hong Kong Polytechnic University Microfluidic mixing using continuous acceleration/deceleration methodology
EP2133149A1 (fr) * 2008-06-13 2009-12-16 F.Hoffmann-La Roche Ag Dispositif d'étiquetage sur disque
EP2329877A1 (fr) * 2009-12-04 2011-06-08 Roche Diagnostics GmbH Elément micro-fluidique destiné à l'analyse d'un échantillon de liquide
KR101722548B1 (ko) * 2010-01-29 2017-04-03 삼성전자주식회사 원심력기반의 미세유동장치 및 이를 이용한 유체시료 내 분석대상물질 검출방법
EP2369324A1 (fr) 2010-03-23 2011-09-28 F. Hoffmann-La Roche AG Procédé de fabrication d'un élément de test analytique, élément de test analytique, utilisation d'un élément de test analytique ainsi que système de test analytique
JP5728217B2 (ja) 2010-12-14 2015-06-03 ローム株式会社 マイクロチップおよびそれを用いた検査または分析方法
US9604213B2 (en) 2012-02-13 2017-03-28 Neumodx Molecular, Inc. System and method for processing and detecting nucleic acids
AU2013221701B2 (en) 2012-02-13 2017-02-02 Molecular Systems Corporation Microfluidic cartridge for processing and detecting nucleic acids
US9637775B2 (en) 2012-02-13 2017-05-02 Neumodx Molecular, Inc. System and method for processing biological samples
US11648561B2 (en) 2012-02-13 2023-05-16 Neumodx Molecular, Inc. System and method for processing and detecting nucleic acids
US11485968B2 (en) 2012-02-13 2022-11-01 Neumodx Molecular, Inc. Microfluidic cartridge for processing and detecting nucleic acids
WO2014059134A1 (fr) * 2012-10-11 2014-04-17 Siemens Healthcare Diagnostics Inc. Porteur de maintenance d'automatisation
DK2912174T3 (da) 2012-10-25 2019-08-26 Neumodx Molecular Inc Fremgangsmåde og materialer til isolering af nukleinsyrematerialer
CA3026548C (fr) 2013-04-15 2022-01-04 Becton, Dickinson And Company Dispositif medical pour le prelevement d'un echantillon biologique
CA2909355C (fr) 2013-04-15 2018-07-10 Becton, Dickinson And Company Dispositif de prelevement de fluide biologique et systeme d'analyse et de separation de fluide biologique
AP2016009089A0 (en) * 2013-08-23 2016-03-31 Daktari Diagnostics Inc Microfluidic metering of fluids
CA2932269C (fr) * 2013-12-06 2022-01-25 Ortho Clinical Diagnostics, Inc. Dispositif d'analyse dote d'un orifice de nettoyage
EP2944965A1 (fr) 2014-05-13 2015-11-18 Roche Diagnostics GmbH Cartouche rotative pour mesurer une propriété d'un échantillon biologique
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EP2952258A1 (fr) 2014-06-06 2015-12-09 Roche Diagnostics GmbH Cartouche rotative pour analyser un échantillon biologique
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US11255852B2 (en) 2014-10-30 2022-02-22 Cytiva Sweden Ab Method to determine solvent correction curves
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US11433390B2 (en) * 2017-12-07 2022-09-06 Ion Llc Methods and systems for a capillary device
JP6846388B2 (ja) * 2018-06-26 2021-03-24 シスメックス株式会社 測定用カートリッジおよび送液方法
CN110614126B (zh) * 2018-06-28 2021-04-09 北京中科生仪科技有限公司 一种实现光学检测的微流控芯片及其制作方法
SE542462C2 (en) * 2018-09-20 2020-05-12 Astrego Diagnostics Ab Sample loading cartridge for a microfluidic device
CN111207242B (zh) 2020-04-18 2020-09-01 博奥生物集团有限公司 流体驱动控制阀及使用方法
KR102433675B1 (ko) * 2020-07-02 2022-08-18 주식회사 클리노믹스 입자 여과 장치 및 입자 여과 방법
BE1029228B1 (fr) * 2021-03-22 2022-10-18 Unisensor Dispositif microfluidique

Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5242606A (en) * 1990-06-04 1993-09-07 Abaxis, Incorporated Sample metering port for analytical rotor having overflow chamber
WO1999058245A1 (fr) * 1998-05-08 1999-11-18 Gyros Ab Dispositif microfluidique
US20040265171A1 (en) * 2003-06-27 2004-12-30 Pugia Michael J. Method for uniform application of fluid into a reactive reagent area
WO2005009581A2 (fr) * 2003-07-15 2005-02-03 Nagaoka & Co. Ltd. Procedes et appareil de separation et d'analyse du sang utilisant des membranes sur un biodisque optique

Family Cites Families (14)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE3445816C1 (de) 1984-12-15 1986-06-12 Behringwerke Ag, 3550 Marburg Flaechenfoermiges diagnostisches Mittel
US5160702A (en) * 1989-01-17 1992-11-03 Molecular Devices Corporation Analyzer with improved rotor structure
US5061381A (en) 1990-06-04 1991-10-29 Abaxis, Inc. Apparatus and method for separating cells from biological fluids
US5591643A (en) * 1993-09-01 1997-01-07 Abaxis, Inc. Simplified inlet channels
US6235531B1 (en) * 1993-09-01 2001-05-22 Abaxis, Inc. Modified siphons for improved metering precision
IL108159A (en) * 1993-12-23 1998-02-08 Orgenics Ltd Apparatus for separation, concentration and detection of target molecules in liquid sample
US20020076354A1 (en) 2000-12-01 2002-06-20 Cohen David Samuel Apparatus and methods for separating components of particulate suspension
EP1390144A2 (fr) * 2001-03-19 2004-02-25 Gyros AB Unites structurelles definissant des fonctions fluidiques
AU2003293399A1 (en) * 2002-12-04 2004-06-23 Spinx, Inc. Devices and methods for programmable microscale manipulation of fluids
US20050014249A1 (en) 2003-02-21 2005-01-20 Norbert Staimer Chromatographic analysis on optical bio-discs and methods relating thereto
WO2004095034A1 (fr) 2003-04-23 2004-11-04 Nagaoka & Co., Ltd. Bio-disques optiques comprenant des circuits fluidiques spiraux pour la realisation de dosages
US7390464B2 (en) * 2003-06-19 2008-06-24 Burstein Technologies, Inc. Fluidic circuits for sample preparation including bio-discs and methods relating thereto
WO2005001429A2 (fr) 2003-06-27 2005-01-06 Nagaoka & Co., Ltd. Circuits de fluides et procedes et appareil d'utilisation d'echantillons de sang entier dans des analyses colorimetriques
JP4646204B2 (ja) * 2005-01-27 2011-03-09 ブラザー工業株式会社 検査対象受体、分取装置、及び分取方法

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5242606A (en) * 1990-06-04 1993-09-07 Abaxis, Incorporated Sample metering port for analytical rotor having overflow chamber
WO1999058245A1 (fr) * 1998-05-08 1999-11-18 Gyros Ab Dispositif microfluidique
US20040265171A1 (en) * 2003-06-27 2004-12-30 Pugia Michael J. Method for uniform application of fluid into a reactive reagent area
WO2005009581A2 (fr) * 2003-07-15 2005-02-03 Nagaoka & Co. Ltd. Procedes et appareil de separation et d'analyse du sang utilisant des membranes sur un biodisque optique

Cited By (14)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2010006668A1 (fr) * 2008-07-18 2010-01-21 Roche Diagnostics Gmbh Élément de test pour l'analyse d'un analyte présent dans un échantillon de liquide corporel, système d'analyse et procédé de commande du déplacement d'un liquide contenu dans un canal d'un élément de test
EP2145682A1 (fr) * 2008-07-18 2010-01-20 Roche Diagnostics GmbH Elément de test destiné à l'analyse d'un analyte contenu dans un échantillon de liquide corporel, système d'analyse et procédé de commande du mouvement d'un liquide contenu dans un canal d'un élément de test
EP2198964A1 (fr) 2008-11-06 2010-06-23 F. Hoffmann-Roche AG Procédé destiné à la préparation d'un réactif séché dans un système microfluidique et système microfluidique
CN102239410A (zh) * 2008-12-03 2011-11-09 霍夫曼-拉罗奇有限公司 具有合并的对照和校准区的测试元件
CN102239410B (zh) * 2008-12-03 2015-05-20 霍夫曼-拉罗奇有限公司 具有合并的对照和校准区的测试元件
WO2011027147A1 (fr) * 2009-09-03 2011-03-10 Vivacta Ltd Dispositif de prélèvement d'échantillons de fluide
GB2473425A (en) * 2009-09-03 2011-03-16 Vivacta Ltd Fluid Sample Collection Device
DE102010013752A1 (de) 2010-03-31 2011-10-06 Roche Diagnostics Gmbh Multifunktionelle Detektionsküvette
WO2011120819A1 (fr) 2010-03-31 2011-10-06 Roche Diagnostics Gmbh Élément microfluidique comprenant une chambre de mesure multifonctionnelle
EP2777499A1 (fr) * 2013-03-15 2014-09-17 Ortho-Clinical Diagnostics Inc Dispositif de collecte d'échantillon de fluide rotatif
US9678069B2 (en) 2013-03-15 2017-06-13 Ortho-Clinical Diagnostics, Inc. Rotatable fluid sample collection device
US10041942B2 (en) 2013-03-15 2018-08-07 Ortho-Clinical Diagnostics, Inc. Rotatable fluid sample collection device
EP3474019A4 (fr) * 2016-06-21 2020-05-06 UNIST (Ulsan National Institute of Science and Technology) Dispositif microfluidique
US11484883B2 (en) 2016-06-21 2022-11-01 Unist (Ulsan National Institute Of Science And Technology) Microfluidic device

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EP2069787A1 (fr) 2009-06-17
CA2664565C (fr) 2014-04-01
ES2933349T3 (es) 2023-02-06
JP2010505096A (ja) 2010-02-18
CN101517413B (zh) 2013-11-06
EP2069787B1 (fr) 2019-03-06
WO2008037469A1 (fr) 2008-04-03
JP5502482B2 (ja) 2014-05-28
US20090191643A1 (en) 2009-07-30
ES2724734T3 (es) 2019-09-13
US8470588B2 (en) 2013-06-25
CN101517413A (zh) 2009-08-26
EP3524982B1 (fr) 2022-10-19
EP3524982A1 (fr) 2019-08-14
CA2664565A1 (fr) 2008-04-03

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