WO1998013684A1 - Appareil et procede destines a l'analyse chimique - Google Patents

Appareil et procede destines a l'analyse chimique Download PDF

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Publication number
WO1998013684A1
WO1998013684A1 PCT/GB1997/002661 GB9702661W WO9813684A1 WO 1998013684 A1 WO1998013684 A1 WO 1998013684A1 GB 9702661 W GB9702661 W GB 9702661W WO 9813684 A1 WO9813684 A1 WO 9813684A1
Authority
WO
WIPO (PCT)
Prior art keywords
reaction chamber
centrifuge
chamber
analysis
sample
Prior art date
Application number
PCT/GB1997/002661
Other languages
English (en)
Inventor
Alastair Sibbald
Original Assignee
Central Research Laboratories Limited
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 Central Research Laboratories Limited filed Critical Central Research Laboratories Limited
Priority to EP97943064A priority Critical patent/EP0935745A1/fr
Priority to JP10515430A priority patent/JP2001502793A/ja
Publication of WO1998013684A1 publication Critical patent/WO1998013684A1/fr

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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
    • 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
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N21/00—Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
    • G01N21/01—Arrangements or apparatus for facilitating the optical investigation
    • G01N21/03—Cuvette constructions
    • G01N21/07—Centrifugal type cuvettes
    • 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
    • B01L2200/0621—Control of the sequence of chambers filled or emptied
    • 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
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2300/00—Additional constructional details
    • B01L2300/08—Geometry, shape and general structure
    • B01L2300/0861—Configuration of multiple channels and/or chambers in a single devices
    • B01L2300/0864—Configuration of multiple channels and/or chambers in a single devices comprising only one inlet and multiple receiving wells, e.g. for separation, splitting
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2300/00—Additional constructional details
    • B01L2300/08—Geometry, shape and general structure
    • B01L2300/0861—Configuration of multiple channels and/or chambers in a single devices
    • B01L2300/087—Multiple sequential chambers
    • 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
    • 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

Definitions

  • the present invention relates to an apparatus for, and a method of, chemical analysis, and more particularly, but not exclusively, to bio-chemical analysis.
  • a growing trend in chemical analysis is the development of assay methods and analysis means which are intended for "one-shot" use.
  • the analysis means is disposed of after the analysis has been performed, together with the biological sample itself. This is convenient from an operator's point of view, in that there is no equipment to maintain and calibrate, and it is especially important in respect of hygiene.
  • a further advantage is the elimination of cross-contamination between sequential samples, an important issue in DNA testing.
  • a common feature of wet chemistry analysis systems is that an analyte, together with one or more reagents, passes sequentially through a series of various procedures, such as mixing, filtering, decanting, metering and dividing. More advanced assay methods, such as polymerase chain reaction (PCR) amplification of DNA, require samples to be thermally cycled a number of times, and it is common to use optical means for detecting end products of the reaction or assay.
  • PCR polymerase chain reaction
  • US Patent No. US-A-5, 160,702 (Molecular Devices Corp) describes an analyser wherein a sample for analysis is introduced into a small cell in a synthetic plastics disc. The sample is then moved through a series of adjacent cells by a varying combination of capillary action and centrifugal force, the latter created by spinning the disc about its centre point. Adjacent cells are configured to perform various functions such as separating out solids and differing density materials from the analyte solution. In practice, however, there are several drawbacks when using capillaries formed in moulded plastic devices. Some of these are listed below:
  • Narrow channels are very susceptible to blockage.
  • the wettability of synthetic plastics surfaces (and hence capillary properties) may vary.
  • Multi-part capillary cell assemblies are difficult to join together without creating lateral leakage as a result of capillary action in pathways. 6. Visual observation of any reaction process is difficult because the disc is spinning. 7. There are limitations in the storage and introduction of reagent fluids, because the use of centrifugal forces to release fluids is not selective. For example, if two or more rupturable seals, (which seal volumes of reagent), are activated at a certain g-force, were deployed, then all the seals would be ruptured at the same time. This is because it is not practical to arrange seals which are triggered at different g-forces.
  • centrifugal action to provide a variable g-force has drawbacks, in that the control of electrical power to the motor is difficult and expensive, and requires a relatively large, bulky electric motor.
  • US Patent No.US-A-5, 162,237 discloses a rectangular cassette, into which a blood sample is introduced for mixing with one or more reagents. Mixing is followed by a visual inspection or optical measurement.
  • the cassette is concerned with efficiently mixing the various fluids by oscillating an assembly containing fluid-obstructers back and forth, so that the fluids are intermixed.
  • An object of the present invention is to provide a compact apparatus and method for carrying out wet chemistry assays having a plurality of processing stages, which apparatus and method can be configured for a wide variety of assay types. Additionally, the apparatus is desirably low-cost, easy to operate and suitable for use away from the laboratory bench.
  • apparatus for chemical analysis comprising: a member having formed therein a reaction chamber, which is in fluid communication with at least one analysis cell, at least one reservoir and at least one centrifuge chamber, the at least one centrifuge chamber is adapted to receive a sample via an inlet port, so that, in use, a sample passes from the centrifuge chamber into the reaction chamber when the member is placed in a first orientation; the sample flows from the reaction chamber into a first reservoir when the member is placed in a second orientation; and the sample flows from a reservoir to the reaction chamber when the member is placed in a third orientation; and the sample flows from the reaction cell to at least one analysis cell when the member is placed in a fourth orientation.
  • the first and third orientations are substantially identical, thus the sample is caused or permitted to return to a previous chamber.
  • the member is rotatable in opposite senses at an angular velocity which is less than the angular velocity of a centrifuge which supports the member.
  • the aforementioned apparatus may be used to analyse chemicals and/or in diagnosing diseases.
  • the reservoirs, chambers and pathways may be defined so that they lie at different heights from a base level on the member.
  • Interconnecting fluid pathways or conduits may be sloped or all features may be formed so that they lie on one level.
  • apparatus for chemical analysis comprising: a rotatable member having formed therein a sample inlet port communicating with a centrifuge chamber, a reaction chamber communicating with the centrifuge chamber by a fluid pathway, and at least one analysis cell communicating with the reaction chamber by a fluid pathway, wherein the rotatable member is spun, in use, in order to centrifuge a sample to be analysed within the centrifuge chamber, and wherein the rotatable member may subsequently be stepped for rotation at least partly in a vertical plane through fixed and predetermined arcs of circles so that the sample for analysis flows into the reaction chamber under the influence of gravity for reaction with one or more reagents, and the products of the reaction chamber subsequently flow into the at least one analysis cell.
  • a method of chemical analysis comprising: providing a rotatable member mounted for rotation having at least a component in a vertical plane, the rotatable member having formed therein a centrifuge chamber, a reaction chamber communicating with the centrifuge chamber by a fluid pathway, and at least one analysis cell communicating with the reaction chamber by a fluid pathway, introducing a sample for analysis into the centrifuge chamber and spinning the rotatable member to effect a centrifuge operation on the sample; stopping the member spinning and rotating the member through a first predetermined arc of circle so that centrifuge products are caused or permitted to flow, via a fluid pathway, under the influence of gravity to the reaction chamber, treating the centrifuge products in the reaction chamber with one or more reagents, and rotating the member through a second predetermined arc of circle in order to cause or permit the contents of the reaction chamber to flow under the influence of gravity into the at least one analysis cell.
  • the member experiences a plurality of steps of rotation and counter-rotation so as to cause or permit a sample in the reaction chamber to experience a repeated set of reactions and/or processes.
  • An example of this may be where a sample has bound chemically to a substrate, for example supported on a surface of beads, and repeated steps of washing or rinsing of the beads is effected.
  • a controlled sequence of processing stages can be performed. Samples may be moved under the influence of gravity, through fluid pathways which are of sufficiently large diameter that capillary forces do not obstruct fluid flow. Generally the pathways are approximately 1 mm in diameter. More specifically the pathways are greater than 0.5 mm diameter.
  • the rotatable member is preferably in the form of a flat disc, formed from a synthetic plastics material having at least one surface which is substantially transparent to radiation in the visible waveband.
  • the transparent surface permits visual inspection and facilitates monitoring of progress of reactions.
  • the member is disposable after a single analysis so as to avoid contamination.
  • the reaction chamber contains an aggregate of small glass or ceramic beads, which have been coated with a reagent, for example an antibody, or onto which a reagent may be applied during operation.
  • a reagent for example an antibody
  • a reagent for example an antibody
  • the beads induces natural turbulence when fluids are passed into the reaction chamber and percolate through the matrix defined by the beads.
  • the beads expose a large surface area of reagent to the sample fluid.
  • the inter-bead separation is of the order of tens of microns.
  • the invention provides apparatus for chemical analysis comprising a rotatable member having formed therein a reaction chamber including an aggregate of beads for receiving on their surface a reagent, and at least one analysis cell communicating with the reaction chamber by a fluid pathway, wherein the rotatable member can be stepped for rotation through fixed and predetermined arcs of circle so that the products of the reaction chamber subsequently flow into the at least one analysis cell.
  • liquid reagents are introduced into the reaction chamber by providing in the rotatable member one or more compressible, open-cell, structures, such as sponges, in which a liquid reagent is stored.
  • a piston or other means of receiving and storing liquids may be provided for compressing the open-cell member in order to squeeze therefrom a liquid (which may be a reagent or a rinsing medium) into a fluid pathway communicating with the reaction chamber.
  • a liquid which may be a reagent or a rinsing medium
  • first and second open-cell members are provided in separate cylinders, each containing a different liquid reagent from the other, and both being independently operable by first and second pistons.
  • apparatus for chemical analysis comprising: a rotatable member having formed therein a reaction chamber, at least one analysis cell communicating with the reaction chamber by a fluid pathway and storage means for introducing into the reaction chamber one or more liquids for acting on a sample, the storage means comprising a compressible, open-cell member adapted to be mounted within a chamber, the storage means, in use, contains a liquid, so that on compression the liquid is released into a fluid flow path communicating with the reaction chamber.
  • the invention extends to an adaptor for connecting the member to a centrifuge, the invention also extends to a centrifuge system which is adapted to receive the aforementioned disc member and is capable of being controlled so as to be able to operate selectively in a high speed centrifuge mode and also a relatively low speed stepping mode, thereby enabling relatively slow clockwise and slow counter clockwise rotation of the member.
  • the centrifuge system has a stepper motor which may be directly linked to a main, centrifuge rotor or may be connected thereto by way of a gear system.
  • Control of the system may be manual or by way of a computer.
  • Figure 1 is a plan view of a rotatable disc member
  • Figure 2 shows details of a compressible member for receiving a fluid, together with illustrative views of the principle of operation thereof;
  • Figures 3 and 4 show different views of the method of operation of the apparatus, employing the embodiment shown in Figure 1 ;
  • Figure 5 is a sectional, exploded view showing the disc member, a cap member and a rotor mounting of a centrifuge.
  • FIG. 1 shows the apparatus in the form of a disc member 1.
  • the disc member 1 includes an inlet port 2 communicating with a centrifuge chamber 4, coupled by a fluid pathway 6 to a reaction chamber 8.
  • the reaction chamber 8 is coupled by various fluid pathways 10 to different reservoirs which include: a waste depot chamber 12, an array of analysis cells 16, and first and second liquid injection chambers 18, 20. Breather tubes 22 are also provided.
  • Index mark 24 is a start position from which the sense of rotation of the disc 1 is defined at various angular positions. The purpose of this is explained below.
  • Each analysis cell 16 (fixed-volume metering cell) contains a particular enzyme which reacts with an antigen present in the test sample, causing either a colour change in a solution which supports a sample, or inhibition of induced fluorescence of the solution.
  • Various methods of colorimetric analysis are known, both for visual inspection, and for automated detection and measurement.
  • Pathway 10b to the analysis cells 16 is wide- bore, but outlet bores 25 to the waste depot 14 are narrow-bore, for reasons explained below.
  • Disc 1 subjects an introduced sample (the analyte) to one or more wet-chemistry processing stages, involving wet reagents, dry reagents, or both, so that the sample is processed using similar methods and materials as would be present in a conventional laboratory. This is achieved entirely within the apparatus.
  • the apparatus confers several major benefits, including flexibility of operation, hygienic operation, freedom from cross-contamination between samples, and long shelf-life.
  • the apparatus is in the form of a 70 mm diameter disc, 5 mm thick, although other shapes are equally viable (such as squares or hexagons). Fluid pathways 10a and
  • Injection chambers for storing liquids and dispensing liquids are, (described in detail below with reference to Figure 2), are 3 mm diameter and 10 to 20 mm in length. The dimensions are consistent with processing sample sizes in the range approximately 30 to 500 microlitres.
  • reaction chamber 8 includes an aggregate of glass beads 26 whose diameter is approximately 0.6 mm. This diameter ensures the beads are large enough not to be flushed from the chamber in which they reside, but small enough to provide a reasonably large surface area, accessible easily by diffusion processes within the sample fluid. Ideally all locations in the fluid are within 100 microns of the nearest bead surface. Beads 26 are a convenient vehicle to immobilise chemicals on, because they can be "poured" into place, and also machine-counted. The extreme practical range for bead diameter is 0.1 mm to 3.0 mm. Preferably the diameter of the beads is in the range 0.5 to 1.5 mm.
  • Injection chambers 18 and, 20 each contain a cylindrical reservoir 30 which acts as an injector device. Inside each chamber there is located a foam material 32 having impervious upper and lower faces 34.
  • An absorbent foam plastic, sponge-like material is preferred for the piston body 32: Such material is defined as having an open-pore structure. This means the material absorbs and retains fluids.
  • the upper and lower faces 34 of the piston 32 can also be formed from foam plastic.
  • the upper and lower faces 34 of the piston 32 are impervious so as to prevent evaporation or leakage of any fluid absorbed when the piston body is charged.
  • upper and lower faces comprise silicone rubber materials, or wax/grease impregnated materials. These materials also ensure a good conformal fit to the inside surfaces of the apparatus which define the cylinders).
  • Pistons 32 of this type are made by coating a sheet of absorbent foam material (having a thickness equal to the length of the required pistons) with the impervious materials on the upper and lower surfaces, and then punching out the cylinders with a rotating, hollow drill-type system (not shown).
  • Actuator rods 36 are optionally provided for compressing pistons 32.
  • Alternative actuators means may be provided.
  • the disc 1 has a transparent plate 50 bonded to the body of the disc 1.
  • the lower surface of the disc 1 has a central hemispherical alignment guide 52 and an alignment dog 54 disposed in it's periphery.
  • Guide 52 and dog 54 mate with corresponding guides 62, 64 of disc mount adapter plate 60, adapted to be mounted onto a main rotor element 70 of an electric motor (not shown) by bolts 72 and bolt holes 74.
  • Adapter plate 60 has two diametrically opposed flexible members 66.
  • members 66 can be moved outwardly by finger pressure to allow the disc to be engaged in position in the adapter plate 60, and then allowed to snap back over the disc to retain the disc in position.
  • the rotor is mounted at an angle of 45 degrees to the vertical, so that the disc is also at a similar angle.
  • FIGs 2a to d illustrate diagrammatically the concept of operation of the reservoir 30 and piston 32.
  • a cell is shown containing a foam piston 32, as described above, and a chamber "A", into which reagent is to be injected at a particular time.
  • the piston 32 is partially inserted into the cylinder 30, leaving a short section of the body of the foam piston 32 exposed.
  • a fixed, metered quantity of liquid reagent is added via an automated titrator (not shown) to the exposed foam piston 32.
  • the foam absorbs the reagent, and the piston 32 is then pushed into the cylinder 30, so that the upper, impervious face 34 is flush with (or slightly below) the cell surface, as shown in Figure 2a.
  • the pushrod When the piston has been entirely compressed, the pushrod is withdrawn, and then either the piston remains collapsed, or springs back, absorbing air via breather tube 35 and upper region of chamber "A". This is dependent on materials and cell configuration. In either event, a precise amount of reagent has been injected into the requisite compartment at the chosen time.
  • the injection process can be either fast or slow, depending on requirements, and it can also be carried out in stages (e.g. four, 25% titrations).
  • a blood sample (30 ⁇ l approx.) is injected into centrifuge chamber 4 via the inlet port 2, with disc 1 set to position 180°. In this position, the axis of centrifuge chamber 4 is vertically downwards and liquids tend to remain in the centrifuge chamber.
  • the fixed-volume analysis cells 16 comprise a relatively large-bore inlet port 10b leading to each fixed- volume cell.
  • a relatively narrow-bore outlet tube leads from each cell to a common waste reservoir 14.
  • Such a structure has a fluid impedance which is dependent on its level of fill. Fluid can flow relatively easily into each cell 16 until the narrow-bore section is reached, at which stage the force needed to continue driving the fluid into the cell rises greatly. At this point, the fluid, which flows most readily along the path of lowest resistance, effectively diverts to the conduit leading to an adjacent cell, and so on.
  • each of the cells 16 fills efficiently, one by one. This sequential filling of cells ensures. Very little additional fluid flows in to each cell once it has been filled, and hence the effective volume residing in the cell is well-defined. This may be important from a qualitative measurement point of view.
  • the pathways can be formed so as to define a fluid logic circuit so that, for example, a sample may be divided into two or more volumes and one sub- sample may be directed along a pathway directly to a reaction chamber; whilst another sub-sample may be sent via a delay line to a different chamber in order that it is subjected to a different reaction at a different, predetermined instant.
  • Breather tubes 22 ensure that fluids can move freely by, expelling air ahead of themselves. Breather tubes 22 are configured so that they link non-critical volumes, ensuring any excess fluid does not interfere with the chemical analysis.
  • the disc-shaped embodiment of the invention may be conveniently manufactured in the form of two synthetic plastics mouldings, representing an upper-half and lower-half of the final assembly.
  • the lower-half moulding contains indentations and recesses which define chambers, reservoirs, cells, conduit pathways and lower halves of injection cylinders.
  • the upper-half moulding contains only indentation defining the upper halves of the injection cylinders. Additional elements can be located in the appropriate cavities in either lower-half.
  • the upper-half of the disc is bonded to the lower-half.
  • Foam piston injectors either pre-loaded with reagent or dry for subsequent loading prior to distribution.
  • Absorber material for waste reservoirs or depots, such as porous paper pads.
  • Bonding of the upper and lower halves may be achieved either using a porous-gasket technique described in the Applicant's granted US Patent No US-A-4,865,716, or modification thereof.
  • a gasket of tissue paper or polymer is impregnated with a wax or low-temperature thermal glue, and punched to shape, such that apertures are created in areas to be kept free from glue.
  • the gasket is sandwiched between upper- and lower-halves of disc 1, by snapping the two halves together.
  • the assembly is then thermally cycled above the melt point of the wax (typically 55 °C) or glue (typically 110 G C), thereby sealing the arrangement.
  • Mechanical registration features moulded into both halves of the disc assembly ensure very accurate alignment, and a "snap-fit".
  • the present invention at least in the preferred embodiment, has the following advantages:
  • the invention can be tailored to a wide variety of different assays, and is not specific to a single type.
  • Hand-held (machine-free) versions of the invention are possible (for field- work and third-world use), wherein a credit-card sized version in the form of a square, pentagon or hexagon or the like can be stood on any of its edge(s), thus allowing manual rotation and positioning for the appropriate time periods and/or appropriate orders.
  • Internal fluid-dispensing means is selective: thus several different reagents can be administered at different times, and at different rates.
  • the internal fluid-dispensing means is accurate.
  • the internal fluid-dispensing means is hermetically secure, thus providing a long shelf-life.
  • Corners of pathways are rounded or curved so as to prevent build-up of substances at or around sharp corners. This also improves removal of articles from moulds during manufacture. 1 1.
  • the wettability of surfaces of pathways can be improved by coating them with a fine layer of sugar or similar substance.
  • the apparatus may be formed from a material which is transparent to a band of radiation.
  • An optical reader may be positioned adjacent analysis cells 16 so that a colour change in cell may be monitored or detected. The signal indicative of any colour change may be absorbed or reflected by the sample in the cell.
  • Optical readers such as an optical fibre, can be arranged to sample and detect colour variations, convert them into an electrical signal for display, analysis or transmittal to a remote laboratory for analysis. In the latter case transmittal may be, for example, via a telephone link or via a GSM connection.
  • a system comprising the disc member, a reader and means for converting signals obtained by the reader into electronic signals, may be connected to a high speed electronic data link such as a modem.
  • a high speed electronic data link such as a modem.
  • the system could be used to transmit signals to a remote laboratory for an export opinion of the analysis.
  • a remote analysis may be performed using a computer, programmed to receive signals from the analysis cells.
  • the computer thus programmed may be capable of performing hundreds of analysis or diagnosis.

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  • Chemical & Material Sciences (AREA)
  • Health & Medical Sciences (AREA)
  • Analytical Chemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Immunology (AREA)
  • Biochemistry (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • General Physics & Mathematics (AREA)
  • Physics & Mathematics (AREA)
  • Pathology (AREA)
  • Hematology (AREA)
  • Clinical Laboratory Science (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Dispersion Chemistry (AREA)
  • Automatic Analysis And Handling Materials Therefor (AREA)
  • Investigating Or Analysing Biological Materials (AREA)
  • Centrifugal Separators (AREA)

Abstract

L'invention concerne un appareil et un procédé destinés à l'analyse chimique. Dans un mode de réalisation préféré, l'invention comprend un élément en forme de disque (1) qui possède une chambre (8), des voies (10a et b), un réservoir (12) ainsi que des cellules d'analyse (16) intégralement formés à l'intérieur de l'élément. On introduit un échantillon sanguin dans l'appareil, qui le centrifuge dans le but de séparer les globules sanguins de sérum. On soumet ensuite le sérum à un certain nombre d'opérations et/ou de tests par exemple, afin de déterminer l'état du sérum. L'invention résout certains problèmes présents dans les systèmes existant dans l'état actuel de la technique, grâce à sa capacité de répéter certains opérations, par exemple un test ou des réactions cycliques, en provoquant ou en permettant l'écoulement d'un échantillon dans une région ou un espace, puis en le faisant s'en déverser, et en l'y faisant entrer à nouveau. Ainsi, le lavage et le rinçage sont possibles. Eventuellement des pistons étanches (32) logés dans le disque (1) contiennent des solvants ou des réactifs liquides ou de l'eau. On peut disposer dans une chambre de réaction une matrice de billes (26) dont la surface aura été recouverte avec un réactif.
PCT/GB1997/002661 1996-09-28 1997-09-29 Appareil et procede destines a l'analyse chimique WO1998013684A1 (fr)

Priority Applications (2)

Application Number Priority Date Filing Date Title
EP97943064A EP0935745A1 (fr) 1996-09-28 1997-09-29 Appareil et procede destines a l'analyse chimique
JP10515430A JP2001502793A (ja) 1996-09-28 1997-09-29 化学分析用の装置及び方法

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
GB9620278.3 1996-09-28
GBGB9620278.3A GB9620278D0 (en) 1996-09-28 1996-09-28 Apparatus for chemical analysis

Publications (1)

Publication Number Publication Date
WO1998013684A1 true WO1998013684A1 (fr) 1998-04-02

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PCT/GB1997/002661 WO1998013684A1 (fr) 1996-09-28 1997-09-29 Appareil et procede destines a l'analyse chimique

Country Status (5)

Country Link
EP (1) EP0935745A1 (fr)
JP (1) JP2001502793A (fr)
KR (1) KR20000048669A (fr)
GB (1) GB9620278D0 (fr)
WO (1) WO1998013684A1 (fr)

Cited By (22)

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US10539582B2 (en) 2014-06-30 2020-01-21 Phc Holdings Corporation Substrate for sample analysis, sample analysis device, sample analysis system, and method for removing liquid from liquid that contains magnetic particles
CN111122893A (zh) * 2018-10-31 2020-05-08 天亮医疗器材股份有限公司 检测卡匣、检测方法及检测装置
US11467069B2 (en) 2017-01-05 2022-10-11 Shimadzu Corporation Sampling chip dividing instrument
EP4124385A1 (fr) * 2021-07-26 2023-02-01 Helaxy Inc. Arrangement et procede pour la purification et l'amplification combinees d'acides nucleiques

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JP5459265B2 (ja) * 2011-05-30 2014-04-02 ブラザー工業株式会社 検査対象受体、その検査対象受体を備えた液体混合システム、及びその液体混合システムを用いる液体混合方法
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EP1188483A2 (fr) * 2000-08-30 2002-03-20 Wardlaw Partners LP Récipient pour contenir des liquides biologiques pour l'analyse
EP1188483A3 (fr) * 2000-08-30 2002-10-16 Wardlaw Partners LP Récipient pour contenir des liquides biologiques pour l'analyse
WO2002087762A1 (fr) * 2001-04-30 2002-11-07 The Secretary Of State For Defence Systeme de distribution de reactifs
US9067209B2 (en) 2001-04-30 2015-06-30 The Secretary Of State For Defense Reagent delivery system
US8815181B2 (en) 2001-04-30 2014-08-26 The Secretary Of State For Defence In Her Britannic Majesty's Government Of The United Kingdom Of Great Britain And Northern Ireland Reagent delivery system
US8778283B2 (en) 2001-04-30 2014-07-15 The Secretary Of State For Defence Reagent delivery system
US7638097B2 (en) 2001-04-30 2009-12-29 The Secretary Of State For Defence Reagent delivery system
US8298497B2 (en) 2001-04-30 2012-10-30 The Secretary Of State For Defence Reagent delivery system
US7749442B2 (en) 2001-12-14 2010-07-06 Arkray, Inc. Sample measuring device
US7384602B2 (en) 2002-05-08 2008-06-10 Hitachi High-Technologies Corporation Chemical analysis apparatus and genetic diagnostic apparatus
EP1669733A4 (fr) * 2003-10-03 2012-11-21 Nat Inst For Materials Science Procede utilisant une puce et puce d'essai
EP1669733A1 (fr) * 2003-10-03 2006-06-14 National Institute for Materials Science Procede utilisant une puce et puce d'essai
US7955863B2 (en) 2003-12-08 2011-06-07 Applied Biosystems, Llc Microfluidic device and material manipulating method using same
US7329391B2 (en) 2003-12-08 2008-02-12 Applera Corporation Microfluidic device and material manipulating method using same
WO2005056188A1 (fr) * 2003-12-08 2005-06-23 Applera Corporation Dispositif microfluidique et procede de manipulation de matieres utilisant un tel dispositif
US8431384B2 (en) 2004-05-24 2013-04-30 Genvault Corporation Stable protein storage and stable nucleic acid storage in recoverable form
EP2175278A4 (fr) * 2007-07-27 2011-05-18 Panasonic Corp Dispositif pour analyse, et appareil et procédé d'analyse utilisant le dispositif
EP2175278A1 (fr) * 2007-07-27 2010-04-14 Panasonic Corporation Dispositif pour analyse, et appareil et procédé d'analyse utilisant le dispositif
CN101680906B (zh) * 2007-07-27 2013-10-02 松下电器产业株式会社 分析用仪器和使用该分析用仪器的分析装置及分析方法
US8283165B2 (en) 2008-09-12 2012-10-09 Genvault Corporation Matrices and media for storage and stabilization of biomolecules
US9637513B2 (en) 2008-09-12 2017-05-02 Gentegra Llc Matrices and media for storage and stabilization of biomolecules
US8951719B2 (en) 2008-09-12 2015-02-10 Gentegra, LLC. Matrices and media for storage and stabilization of biomolecules
US10160997B2 (en) 2008-09-12 2018-12-25 Gentegra Llc Matrices and media for storage and stabilization of biomolecules
WO2010107719A1 (fr) * 2009-03-18 2010-09-23 Cardinal Health 207, Inc. Appareil et procédé de mesure de marqueur biométrique de condensat de respiration expirée
US9289764B2 (en) 2010-12-20 2016-03-22 Boehringer Ingelheim Microparts Gmbh Method for mixing at least one sample solution having at least one reagent, and device
US9562262B2 (en) 2011-03-08 2017-02-07 UNIVERSITé LAVAL Fluidic centripetal device
US11123730B2 (en) 2011-03-08 2021-09-21 Universite Laval Fluidic centripetal device
US10427158B2 (en) 2011-03-08 2019-10-01 UNIVERSITé LAVAL Fluidic centripetal device
US10539582B2 (en) 2014-06-30 2020-01-21 Phc Holdings Corporation Substrate for sample analysis, sample analysis device, sample analysis system, and method for removing liquid from liquid that contains magnetic particles
US10539560B2 (en) 2014-06-30 2020-01-21 Phc Holdings Corporation Substrate for sample analysis, and sample analysis apparatus
US10309976B2 (en) 2014-06-30 2019-06-04 Phc Holdings Corporation Substrate for sample analysis, sample analysis device, sample analysis system, and program for sample analysis system
US10520521B2 (en) 2014-06-30 2019-12-31 Phc Holdings Corporation Substrate for sample analysis, sample analysis device, sample analysis system, and program for sample analysis system
US10539583B2 (en) 2014-12-12 2020-01-21 Phc Holdings Corporation Substrate for sample analysis, sample analysis device, sample analysis system, and program for sample analysis system
USD799715S1 (en) 2015-10-23 2017-10-10 Gene POC, Inc. Fluidic centripetal device
EP3399319A4 (fr) * 2015-12-28 2019-01-02 PHC Holdings Corporation Substrat d'analyse d'échantillons, dispositif d'analyse d'échantillons, système d'analyse d'échantillons, et programme pour système d'analyse d'échantillons
CN108431610A (zh) * 2015-12-28 2018-08-21 普和希控股公司 试样分析用基板、试样分析装置、试样分析系统和试样分析系统用程序
US11262356B2 (en) 2015-12-28 2022-03-01 Phc Holdings Corporation Specimen analysis substrate, specimen analysis device, specimen analysis system, and program for specimen analysis system
CN108431610B (zh) * 2015-12-28 2022-04-05 普和希控股公司 试样分析用基板、试样分析装置、试样分析系统和记录介质
US11467069B2 (en) 2017-01-05 2022-10-11 Shimadzu Corporation Sampling chip dividing instrument
CN111122893A (zh) * 2018-10-31 2020-05-08 天亮医疗器材股份有限公司 检测卡匣、检测方法及检测装置
CN111122893B (zh) * 2018-10-31 2024-04-12 天亮医疗器材股份有限公司 检测卡匣、检测方法及检测装置
EP4124385A1 (fr) * 2021-07-26 2023-02-01 Helaxy Inc. Arrangement et procede pour la purification et l'amplification combinees d'acides nucleiques
WO2023006694A1 (fr) * 2021-07-26 2023-02-02 Helaxy Inc. Ensemble et procédé pour la purification et l'amplification d'acides nucléiques combinés

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GB9620278D0 (en) 1996-11-13
EP0935745A1 (fr) 1999-08-18
KR20000048669A (ko) 2000-07-25

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