WO2004045772A2 - Recipients de reaction et appareil de reaction utilise avec lesdits recipients - Google Patents

Recipients de reaction et appareil de reaction utilise avec lesdits recipients Download PDF

Info

Publication number
WO2004045772A2
WO2004045772A2 PCT/GB2003/005041 GB0305041W WO2004045772A2 WO 2004045772 A2 WO2004045772 A2 WO 2004045772A2 GB 0305041 W GB0305041 W GB 0305041W WO 2004045772 A2 WO2004045772 A2 WO 2004045772A2
Authority
WO
WIPO (PCT)
Prior art keywords
vessel
reaction
vessels
thermopile
outer layer
Prior art date
Application number
PCT/GB2003/005041
Other languages
English (en)
Other versions
WO2004045772A3 (fr
Inventor
James Howell
Ben Webster
Roderic Fuerst
Original Assignee
Bg Research 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 Bg Research Limited filed Critical Bg Research Limited
Priority to AU2003286253A priority Critical patent/AU2003286253A1/en
Publication of WO2004045772A2 publication Critical patent/WO2004045772A2/fr
Publication of WO2004045772A3 publication Critical patent/WO2004045772A3/fr

Links

Classifications

    • 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
    • G01N21/0332—Cuvette constructions with temperature control
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J19/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
    • B01J19/0093—Microreactors, e.g. miniaturised or microfabricated reactors
    • 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
    • B01L3/508—Containers for the purpose of retaining a material to be analysed, e.g. test tubes rigid containers not provided for above
    • B01L3/5085—Containers for the purpose of retaining a material to be analysed, e.g. test tubes rigid containers not provided for above for multiple samples, e.g. microtitration plates
    • B01L3/50851—Containers for the purpose of retaining a material to be analysed, e.g. test tubes rigid containers not provided for above for multiple samples, e.g. microtitration plates specially adapted for heating or cooling samples
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L7/00—Heating or cooling apparatus; Heat insulating devices
    • B01L7/52—Heating or cooling apparatus; Heat insulating devices with provision for submitting samples to a predetermined sequence of different temperatures, e.g. for treating nucleic acid samples
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L9/00—Supporting devices; Holding devices
    • B01L9/52—Supports specially adapted for flat sample carriers, e.g. for plates, slides, chips
    • B01L9/523—Supports specially adapted for flat sample carriers, e.g. for plates, slides, chips for multisample carriers, e.g. used for microtitration plates
    • 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
    • G01N21/15—Preventing contamination of the components of the optical system or obstruction of the light path
    • 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
    • G01N21/17—Systems in which incident light is modified in accordance with the properties of the material investigated
    • G01N21/25—Colour; Spectral properties, i.e. comparison of effect of material on the light at two or more different wavelengths or wavelength bands
    • G01N21/251—Colorimeters; Construction thereof
    • G01N21/253—Colorimeters; Construction thereof for batch operation, i.e. multisample apparatus
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J2219/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
    • B01J2219/00781—Aspects relating to microreactors
    • B01J2219/00788—Three-dimensional assemblies, i.e. the reactor comprising a form other than a stack of plates
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J2219/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
    • B01J2219/00781—Aspects relating to microreactors
    • B01J2219/00873—Heat exchange
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J2219/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
    • B01J2219/00781—Aspects relating to microreactors
    • B01J2219/0095—Control aspects
    • B01J2219/00952—Sensing operations
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J2219/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
    • B01J2219/00781—Aspects relating to microreactors
    • B01J2219/0095—Control aspects
    • B01J2219/00952—Sensing operations
    • B01J2219/00954—Measured properties
    • B01J2219/00961—Temperature
    • 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
    • B01L2200/02—Adapting objects or devices to another
    • B01L2200/025—Align devices or objects to ensure defined positions relative to each other
    • 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
    • B01L2200/14—Process control and prevention of errors
    • 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
    • B01L2300/04—Closures and closing means
    • B01L2300/041—Connecting closures to device or container
    • B01L2300/042—Caps; Plugs
    • 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
    • B01L2300/0654—Lenses; Optical fibres
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2300/00—Additional constructional details
    • B01L2300/08—Geometry, shape and general structure
    • B01L2300/0809—Geometry, shape and general structure rectangular shaped
    • B01L2300/0829—Multi-well plates; Microtitration plates
    • 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
    • B01L2300/0848—Specific forms of parts of containers
    • B01L2300/0858—Side walls
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2300/00—Additional constructional details
    • B01L2300/08—Geometry, shape and general structure
    • B01L2300/0887—Laminated structure
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2300/00—Additional constructional details
    • B01L2300/18—Means for temperature control
    • B01L2300/1805—Conductive heating, heat from thermostatted solids is conducted to receptacles, e.g. heating plates, blocks
    • B01L2300/1827—Conductive heating, heat from thermostatted solids is conducted to receptacles, e.g. heating plates, blocks using resistive heater
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L7/00—Heating or cooling apparatus; Heat insulating devices
    • B01L7/54—Heating or cooling apparatus; Heat insulating devices using spatial temperature gradients
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B29—WORKING OF PLASTICS; WORKING OF SUBSTANCES IN A PLASTIC STATE IN GENERAL
    • B29C—SHAPING OR JOINING OF PLASTICS; SHAPING OF MATERIAL IN A PLASTIC STATE, NOT OTHERWISE PROVIDED FOR; AFTER-TREATMENT OF THE SHAPED PRODUCTS, e.g. REPAIRING
    • B29C45/00—Injection moulding, i.e. forcing the required volume of moulding material through a nozzle into a closed mould; Apparatus therefor
    • B29C45/16—Making multilayered or multicoloured articles
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B29—WORKING OF PLASTICS; WORKING OF SUBSTANCES IN A PLASTIC STATE IN GENERAL
    • B29K—INDEXING SCHEME ASSOCIATED WITH SUBCLASSES B29B, B29C OR B29D, RELATING TO MOULDING MATERIALS OR TO MATERIALS FOR MOULDS, REINFORCEMENTS, FILLERS OR PREFORMED PARTS, e.g. INSERTS
    • B29K2995/00—Properties of moulding materials, reinforcements, fillers, preformed parts or moulds
    • B29K2995/0003—Properties of moulding materials, reinforcements, fillers, preformed parts or moulds having particular electrical or magnetic properties, e.g. piezoelectric
    • B29K2995/0005—Conductive
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B29—WORKING OF PLASTICS; WORKING OF SUBSTANCES IN A PLASTIC STATE IN GENERAL
    • B29K—INDEXING SCHEME ASSOCIATED WITH SUBCLASSES B29B, B29C OR B29D, RELATING TO MOULDING MATERIALS OR TO MATERIALS FOR MOULDS, REINFORCEMENTS, FILLERS OR PREFORMED PARTS, e.g. INSERTS
    • B29K2995/00—Properties of moulding materials, reinforcements, fillers, preformed parts or moulds
    • B29K2995/0003—Properties of moulding materials, reinforcements, fillers, preformed parts or moulds having particular electrical or magnetic properties, e.g. piezoelectric
    • B29K2995/0007—Insulating
    • 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
    • G01N21/15—Preventing contamination of the components of the optical system or obstruction of the light path
    • G01N2021/158—Eliminating condensation

Definitions

  • the invention relates to an improved reaction vessel and apparatus for heating such vessels and monitoring reactions within such vessels and is applicable with particular advantage to temperature dependant biological or chemical reactions, and even more particularly to reactions such as the polymerase chain reaction (PCR).
  • PCR polymerase chain reaction
  • reaction vessels are in the form of a tray, known as a microtitre plate, made up of an array of vessels. . In one standard microtitre plate, 96 vessels are formed in one array.
  • the apparatus includes means to monitor the temperature and to control the heating power applied to the reaction vessel contents.
  • Many reactions, especially biological reactions such as PCR, can be monitored by optical interrogation or detection. This optical detection may be colorimetric or fluorometric (including techniques such as time-resolved fluorescence).
  • Reaction vessels particularly suited to reduced volume biological reactions heated by electrically conducting polymers are described in International Patent Application Publication No PCT/GB97/03187 and a particular such vessel is described in GB Patent specification 2333250.
  • An array of such vessels are introduced into reaction apparatus which includes means to allow heating of the vessels, and means to observe reactions occurring in the vessels.
  • the vessel may be made of an electrically conducting polymer or surrounded by a sheath of electrically conducting polymer and be accordingly heated by an electrical current flowing through the electrically conducting polymer.
  • the electrical current can be supplied via connection points from an electrical supply.
  • the vessel has a cap which extends into the body of the vessel to form a space of consistent cross section of capillary dimensions.
  • the lid or base of the vessel may be transparent to provide a light guide/window through which the reactions within the vessel can be monitored.
  • a problem which is apt to occur with such a window arises from a temperature differential between the reaction contents and the inner surface of the light guide or window (which is in contact with the vapour from the reaction contents).
  • vapour produced by the hot reaction contents cools on the cooler inner surface of the window and condenses, thus obscuring the contents from the monitor means
  • a possible arrangement also includes a cap having a channel into which a thermocouple, thermistor, or other contact-based temperature sensor may be inserted to monitor the temperature within a particular reaction vessel, to allow individual temperature control.
  • thermometric system A problem that may occur with such a thermometric system is that there can be a large latent period between the application of power to the ECP by the heating control system and the detection of resultant heating by the temperature sensor.
  • the ECP responds quickly to energy input, as a result the ECP can heat excessively during the latent period. This excessive heating may result in irreversible damage to the vessel and/or vessel contents.
  • PCR reactions for example, are sensitive to inaccuracies in temperature control.
  • a reaction vessel for containing a chemical or biochemical reaction and incorporating heating means for effecting the reaction and having a lid, the lid having a window whereby the contents of the vessel can be interrogated, the arrangement being such that the heating means also operates to ensure that the window is kept vapour-free for the interrogation.
  • the heating means for effecting the reaction may comprise a layer, preferably an outer layer, which may be composed of an electrically conducting polymer.
  • the lid may have a nose which projects into the vessel, the tip of the nose defining a window through which light may pass for optical monitoring of the vessel contents and the heating means surrounds the vessel and the lid so that the lid window is heated.
  • 'window' is intended to encompass any barrier partially or completely transparent to light and includes light guides.
  • the outer layer may comprise an open ended tube surrounding the elongate surfaces of the inner layer preferably the outer layer itself is in the form of an elongate vessel so that the base of the inner layer is also covered by electrically conducted polymer to form a contact area.
  • the inner layer is preferably constructed from a polymer which provides a suitable surface for contact with the liquid contents, allows for biological/chemical reactions to take place optimally and provides optimal thermal coupling between the contents and the ECP heating layer.
  • a polymer which provides a suitable surface for contact with the liquid contents, allows for biological/chemical reactions to take place optimally and provides optimal thermal coupling between the contents and the ECP heating layer.
  • such material may comprise polypropylene, polythene, polyvinylpropylene, glass or other materials that can be used in biological/chemical reaction processes. The choice of such material is readily apparent to the skilled addressee of the specification
  • the outer layer preferably constructed from a material allowing the vessel to be heated by application of an electrical voltage differential with resultant heat produced evenly and predictably so as to heat the liquid contents evenly and predictably.
  • the material provides a low resistance electrical contact.
  • a suitable material is a polypropylene containing carbon fibre and carbon black. It can however be any electrically conducting material with conductive particles such as carbon, metal, within an inert base resin such as polypropylene, polyvinylpropylene or nylon.
  • the outer layer is black to provide a vessel having black body external surface properties, which is a good radiating source. This is particularly suited to systems where non-contact temperature measurement is required (for instance in accordance with the fourth aspect of the invention).
  • the vessel is designed to contain the entire body of heated liquid in a minimally tapered cylinder, the taper angle being chosen for the optical application and ease of moulding if the vessel is produced by a moulding method.
  • the taper angle is of the order of 1-2° and the thickness of the outer layer is between 0.1 and 1 mm.
  • the liquid heating region is apt to be the region of most stringent manufacturing tolerance and is carefully calibrated and compensated for the variation in the vessel radius to give even heating without hot spots. This means that the liquid at each depth in the vessel is then subjected to conditions as close as possible to those at any other depth.
  • the vessel has advantageously the smallest radius practical given the taper angle, to reduce to a minimum the maximum distance from any point in the vessel contents to the nearest heated internal surface, hence reducing temperature lag between the outer layer and vessel contents while heating or cooling.
  • the maximum radius of the working portion of the vessel may accordingly be 1 to 4mm.
  • the vessel is heated at the same power per unit area at all depths, to produce even heating by means of the method of 'Tube Radius Compensation'.
  • the outer layer is arranged so as to provide an even heating power per unit area of contact with the inner layer across the interface between the outer and inner layers. This in turn will produce an even heating of the liquid contents, providing optimal heating characteristics. This characteristic is important to the success of processes like PCR.
  • the thickness of the outer layer may be varied so as to precisely maintain a given cross sectional area of the outer layer, perpendicular to the direction of flow of electrical current through the outer layer.
  • the reaction vessel is constructed for use in apparatus in accordance with a fourth aspect of the invention (set out below) with the base of the vessel and an upper region thereof providing electrical contact areas.
  • the outer layer is constructed so as to integrate two contact areas, allowing a low resistance reliable contact to be formed from a pair of external contacts to the outer layer. These areas are advantageously arranged to reduce heating at the contact point, due to contact resistance, to a minimum, and to allow for electrical contact to be made to both areas by pressing the vessel vertically downwards into a suitably constructed contact pack. In this way an array of vessels can also be easily and simultaneously connected to an array of contacts, including but not limited to a microtitre plate application.
  • the base of the vessel forms the lower contact region.
  • the outer layer at the base of the vessel may thus be thicker than the heating regions to reduce possible heating at contact points to a minimum, and to provide for robust contact.
  • the upper contact region is located above the heating regions, consisting of a thicker horizontal ridge in the outer layer. This allows for an upper electrical contact to press vertically against the contact region for assured contact with minimum heating at the contact point.
  • the vessel may include sections of different radius, in which case the vessel may include at least one transition area where the inner and outer layers are thicker.
  • One application for this is to provide a larger radius section for insertion of the lid.
  • the transition areas may be given a thicker inner and outer layer.
  • the thicker inner layer allows margin for some erosion of the inner layer during the moulding process. This margin prevents contamination as a result of the transfer of material from the outer layer to the inner surface of the vessel.
  • a thicker outer layer in the transitional regions ensures that the current density (current per unit cross-sectional area) flowing through the region is lower than in heating regions, producing less heating and avoiding hot spots.
  • a method of manufacture of a reaction vessel comprising the steps of: a) injection moulding an inner tubular vessel having a base thicker than the walls of the tube in cross section; and b) injection moulding an outer layer of an electrically conducting polymer about the inner tubular vessel, with the outer layer also having a base thicker than its walls.
  • the materials used for the inner tubular vessel formed in accordance with this second aspect of the invention may be any injection mouldable polymer, preferably they comprise one of a polypropylene, polythene, polyvinylpropylene, or other materials suitable for use in biological and/or chemical reaction processes.
  • the outer layer is a polypropylene containing carbon fibre and carbon black. It can be any electrically conducting material with conductive particles such as carbon, metal, within an inert base resin such as polypropylene, polyvinylpropylene or nylon. In the case where carbon fibres are used, preferably these are milled or otherwise processed to produce an optimal fibre length. Use of shorter fibre length facilitates moulding by reducing the tendency of the fibres to block the moulding apparatus.
  • Moulding of the inner layer first followed by moulding of the outer layer greatly reduces the probability of contamination of the inner layer by the outer layer material, especially when the vessel design is optimised to prevent the outer layer moulding process from damaging the inner surface. Moulding in the reverse order may result in washing of the surface contaminants or material from the outer layer by the inner layer material, which can contaminate the inner layer and hence the liquid contents within the reaction vessel.
  • the thicker inner and outer layers ensure that if erosion of the inner layer occurs during outer layer moulding, the inner layer will still be sufficient to prevent contamination of the liquid contents. Erosion of the inner layer can be worse at the base of the reaction vessel, near the injection point.
  • the vessel includes sections of different radius as proposed in relation to the first aspect of the invention.
  • the radius change region has a thicker cross section both at the inner and outer layer. This allows for some erosion of the inner vessel as the outer layer material flows around the increased radius of inner layer material.
  • the thicker cross section also reduces possible breakage/ shearing of the carbon fibres. Since the final layer thickness is hard to predict, the thicker outer layer ensures that minimal heating will occur. This protects against the possibility of the outer layer becoming thinner in this region than in the region surrounding the main body of the inner vessel forming the liquid heating region, which could produce an undesirably high temperature.
  • reaction apparatus in which a plurality of reaction vessels are received and the reactions within monitored, including a plurality of vessel receiving stations, each for receiving a reaction vessel and for each receiving station a sensor, preferably a thermopile sensor, arranged spaced from the station so that when a vessel is at the station the sensor measures the temperature of the vessel, but is not in contact with the vessel.
  • a sensor preferably a thermopile sensor
  • thermopiles are preferably equidistant from surrounding vessels to minimise the chance of physical contact.
  • the maximum distance can be determined by the sensitivity of the thermopile and its field of view. The further away the thermopile is placed, the less radiation is received from the vessel.
  • the distance of the thermopile sensor to the vessel is between 0.5mm and 30mm. In the context of microtitre vessels having a maximum diameter of 1 cm, this distance is under 1 cm.
  • the reaction vessels are in accordance with the first aspect of the invention and include an outer layer which provides black body external surface properties which facilitates the non-contact temperature measurement.
  • the reaction apparatus receives a standard array of reaction vessels in a microtitre plate, usually 96 vessels, or integer multiples thereof, wherein the reaction vessels may be arranged in an array which may be square/rectangular or other geometric shape that allows for optimum conditions to be met.
  • the plurality of the thermopile sensors of the apparatus are also arranged in an array with their axes aligned, so that when the vessels are in their stations, the thermopile sensor for that station is pointed at the outer surface of the corresponding vessel, but not in direct physical contact with any vessel.
  • the axis of the centre of the field of view of each sensor is inclined at 45° to the major axis of the microtitre plate and lies in a horizontal plane. This allows the thermopile sensors themselves to fit into the spaces between the vessels in the array with a minimum of interference to airflow over the surface of the vessels.
  • such thermopile sensors are mounted upon a printed circuit board including bores through which the reaction vessels pass.
  • thermopile sensor comprises a thermopile encapsulated in a 'can' with a window in the can allowing a specific wavelength range of radiation particularly infra-red radiation to enter the can window from the measured reaction vessel only, causing the thermopile to -produce a signal.
  • the signal from the thermopile is read via a pair of electrical contacts. This provides a reading related to the amount of infrared radiation being absorbed by the thermopile.
  • each thermopile sensor package also includes an internal embedded temperature sensor, which allows measurement of the local temperature of the thermopile and encapsulation, via further electrical contacts. This provides for compensation of the reading to produce an accurate final temperature.
  • the thermopile sensor could alternatively have an external temperature sensor, say externally bonded to the can. In some cases the thermopiles could have their temperatures regulated in some way that they did not require individual thermistors.
  • each thermopile sensor has a field of view restricted to a portion of the outer surface of the vessel whose temperature is to be measured.
  • This may be provided by an aperture, preferably made from a material which is a good IR reflector, including but not limited to copper or aluminium, shaped with a window allowing access of infra red radiation to the thermopile sensor only from the desired region of the specific reaction vessel whose temperature is being measured by the sensor.
  • the size of the aperture depends upon the size and position of the sensor and vessel but it is preferably arranged so that its field of view covers only the heated part of the vessel and specifically blocks the view of everything else, particularly other vessels at different temperatures.
  • the aperture may be separated from the thermopile or in mechanical contact with the device, for example being fixed onto the thermopile can as a cap.
  • reaction apparatus for receiving and to allow heating of a plurality of reaction vessels in a plurality of vessel receiving stations, including a foraminous upper contact sheet having a plurality of bores, each bore defining the position of a receiving station and a set of foramens for providing air pathways, and a foraminous lower contact sheet having a set of foramens for providing air pathways and having mounted upon it a plurality of electrical contact pads, each pad aligned with a bore of the upper contact sheet, such that a reaction vessel inserted into and contacting a bore of the upper contact sheet will be pushed through to contact an underlying pad on the lower contact sheet to provide means for passing current through the reaction vessel to heat it.
  • the upper contact sheet can be constructed in various ways.
  • a flexible compressible sheet may be covered with a conducting layer to form a surface which forms around the vessel contact areas and affords a good electrical contact, which is maintained even at low contact pressure.
  • the flexible material may be silicon foam, neoprene, sheet rubber or various foams.
  • the flexible/compressible nature of this sheet allows for vessel misalignment to be tolerated.
  • the lower contact pads can be constructed from pieces of the same type of flexible sheet to afford the same benefits.
  • the conductive surface of the contact sheets may be formed by woven metal fabrics including nickel copper alloy woven with rip stop nylon. The choice of other suitable materials is apparent to the skilled addressee.
  • the outer layer of the vessel may be shaped, or treated with a coating or preparation to decrease the resistance of contacts to the vessel surface.
  • the apparatus is applicable with particular advantage to reaction vessels in accordance with the first aspect of the invention.
  • the reaction apparatus includes means to apply a independent and distinct voltage to each reaction vessel station across its pair of contacts. Conveniently this is achieved by including a circuit upon the lower contact sheet allowing the voltage to be applied to the conductive pads to be controlled independently. In this case typically the upper contact sheet is coupled to one voltage only.
  • the upper contact assembly consists of a flexible contact sheet bonded to a substrate using electrically conductive adhesive.
  • An example of a suitable adhesive includes a silver loaded epoxy.
  • the contact pads of the lower PCB may cover at least some areas of the lower surface of the contact sheet to provide an electrical contact with the conductive adhesive.
  • Another example of the contact mounting method is to use contact retention pieces which may be metal and may readily be electrically and physically bonded to the lower PCB or substrate, by a process such as soldering, and which then accept the flexible contact pads.
  • contact arrangements include flexible wire forms, such as helical springs, rings and fingers to achieve the upper and lower contacts; spikes or clamps.
  • reaction vessels include a flange of larger cross section, the flange being part of the outer layer of the vessel such that the flange bears against the outer layer of the upper flexible contact sheet to provide a contact area ridge.
  • the apparatus preferably includes means to provide cooling via airflow. Airflow perpendicular to the plane of the array of vessels provides effective cooling for the reaction vessels. The foramens in the contact apparatus enable such airflow to be readily achieved.
  • thermopile PCB is foraminous with a series of bores through which reaction vessels may pass and a series of foramens for providing air pathways or, preferably, substantially the only bores are those through which the vessels pass but the leave a space around said vessels whereby cooling air is directed over the vessel surface.
  • the foramens may be holes of varying size to allow "tuning" of airflow across each vessel.
  • the airflow may be a fast flowing "jacket" of air near the surface of each vessel providing for rapid cooling. The fast flow rate improves cooling rate, and if the air flows parallel to the surface of the vessel it reduces heating effects on the neighbouring thermopile sensors.
  • the jacket can be used to produce uniform predictable cooling over the entire surface of the vessel.
  • thermopile sensors are more distant from the vessel.
  • the means for providing the airflow may comprise a fan capable of maintaining good airflow at high pressure. This characteristic is suited to forcing air through a convoluted path.
  • reaction vessels are either part of a microtitre plate or are fitted thereto and the plate is offered to the apparatus after the wells have been charged with the reactants and sealed with their caps.
  • a microtitre plate incorporating stations for receiving reaction vessels in accordance with the invention and having foramens surrounding the receiving stations, whereby cooling air can in use be ducted up therethrough adjacent the reaction vessels.
  • microtitre plate is arranged, in relation to the size of the reaction vessels, to grip the latter once these have been offered into their respective receiving stations.
  • microtitre plates according to this feature of the invention may be arranged to provide one or even both of the electrical contacts to the reaction vessels.
  • these microtitre plates may well be disposable items, not least for reasons of maintaining effectiveness and minimising contamination, it is preferred that they are not thus encumbered.
  • an optical monitoring system for a reaction apparatus where the reaction apparatus defines a plurality of receiving stations, each such station receiving a reaction vessel in which a reaction may take place.
  • the optical monitoring system may comprise at least one radiation source. Also provided is a scanning apparatus for directing radiation to vessels in the receiving stations, and for directing radiation emitted by the reaction vessel contents into photometric apparatus.
  • the photometric apparatus directs received radiation to a diffraction grating, and thence to a photomultiplier tube assembly, preferably operating in photon counting mode.
  • the photomultiplier tube assembly may comprise a series of single channel multi-anode photomultiplier tubes but preferably the assembly comprises a multi-channel multi-anode photomultiplier tube (MAPMT).
  • MAPMT multi-channel multi-anode photomultiplier tube
  • Radiation emitted by the vessel contents is dispersed over the pixels of the MAPMT by use of a diffraction grating such that the range of wavelengths of radiation impinging upon a photocathode of the multi-anode photomultiplier tube correlates with the position of the photocathode in the MAPMT.
  • the MAPMT is a 32 pixel linear array over which radiation from around 510-720 nm is dispersed.
  • the optical monitoring system provides for the use of a broad range of fluorophores emitting radiation at wavelengths between about 51 Onm and about 720nm without the need to change filter sets as required in other instrumentation.
  • the use of the PMT and operating it in photon counting mode provides for sensitive detection of radiation facilitating the measurements of low levels of incident fluorescence associated with high sampling frequencies. Measurements using a PMT operating in photon counting mode are less affected by changes in the electromagnetic environment, than if the PMT is operated in analogue mode.
  • the optical monitoring means is preferably an integral part of the reaction apparatus.
  • the light source is a single light source, typically a laser.
  • the laser is a diode pumped solid-state laser (DPSSL) in contrast to the gas lasers used in conventional reaction apparatus and optical monitoring systems.
  • DPSSL diode pumped solid-state laser
  • Preferably means are provided for monitoring the reactions within a plurality of tubes, by directing radiation from a single excitation source to the tubes, and collecting the resultant radiation from the tubes to be measured by a single photometric system.
  • This means may comprise one or more rotatable mirrors, where the configuration of mirrors can be controlled to direct light to and from any specific tube. An array of two mirrors is preferred. The size and bulk of mirror is arranged to be such as to achieve efficient radiation collection with maximum scanning frequency.
  • the acquisition of a full spectrum from each vessel at each sampling point (and same temperature) facilitates the concurrent use of multiple different fluorophores in the array of reaction vessels in the apparatus (including use of multiple different fluorophores within a single vessel) as required by some fluorometric applications.
  • This spectrum may also be acquired in a single operation reading all channels of the MAPMT concurrently, in contrast to systems where readings at different wavelengths must be acquired consecutively, for example by use of a filter wheel or other means. This affords higher sampling rates, and removes effects related to variation in signal due to the acquisition of different wavelengths at different times and/or temperatures.
  • a Fresnel lens may be used in the path of the laser.
  • a Fresnel lens is light, cost- effective and very compact compared to a standard lens of the same diameter and optical properties.
  • the Fresnel lens ensures that the radiation from the excitation source is always directed substantially vertically when it enters each vessel.
  • the rotating mirrors cause the beam to be reflected at an angle, such that it hits the Fresnel lens at a point above the vessel to be illuminated, the Fresnel lens refracts the beam from this point to enter the vessel vertically.
  • the resultant emitted radiation from the vessel is refracted from vertical travel to the correct angle to return to the rotating mirrors and hence to the photometric system.
  • Figure 1 is a section through part of the reaction apparatus holding a reaction vessel
  • Figure 2 is a schematic plan view of the reaction apparatus illustrating a plurality of reaction vessels with their temperature sensor and control means; and Figure 3 is a schematic view of the steps of the method and apparatus for monitoring the optical effects of the reaction. Description of the Preferred Embodiment
  • FIG. 1 can be seen a section of a reaction vessel 10 for receiving reagents in a reaction cavity 10a and having a lid 20 for sealing the vessel.
  • the vessel 10 comprises an inner tubular layer 1 1 having a base 12 and an open top through which reagents are introduced and an outer layer 13 of electrically conducting polymer.
  • the lid 20 has a nose 21 which projects into the body of the vessel 10, the tip of the nose defining a window 22 through which light may pass for optical monitoring of the vessel contents.
  • the outer layer 13 extends from the base 12 of the inner tubular vessel 11 to beyond the level of the outer surface of the lid window 22 such that the lid window 22 is heated. This minimises the possibility of condensation formation, and thus allows for accurate and reproducible optical monitoring of the reactions occurring within the vessel.
  • the inner and outer layers 1 1 and 13 are formed by two shot injection moulding with the two layers of different polymers.
  • the inner layer is polypropylene that provides an optimal surface for contact with the reaction contents to be expected in many biological reactions and also provides good thermal coupling between the outer layer 13 and the contents.
  • the outer layer is polypropylene containing carbon fibre and carbon black, which heats on application of a voltage differential with the heat produced evenly and predictably. In this case the carbon fibres are milled carbon fibres so that the fibres are of optimal length for the manufacturing process for the vessels.
  • the outer layer 13 varies in thickness so that the heat applied to the contents is even.
  • the inner vessel 11 comprises three regions of different radius, namely a lower region 14 in the base region of least radius, a mid region 15 of slightly larger radius and an upper region 16 of greatest radius in the region to the open neck of the vessel 7.
  • a shoulder 17 formed between lower region 14 and mid region 15 provides a seat upon which the lid 20 sits in position.
  • a shoulder 18 between mid region 15 and upper region 16 supports a contact ridge 13c for providing an electrical connection to the vessel.
  • the outer layer 13 extends about the lower region 14 and mid region 15 of the inner vessel and thus itself comprises a lower region 13a of smaller radius than upper region 13b of larger radius.
  • the inner layer 1 1 is heated at the same power per unit area at all depths in regions 14 and 15 to produce even heating of the reaction cavity 10a and window 22 with the thickness of the outer layer being varied to precisely maintain the cross sectional area of the outer layer perpendicular to the direction of flow of electrical current through the outer layer.
  • Both the inner vessel and outer layer have a thicker cross section of in each of the transitional areas formed at shoulders 17 and 18, and at the base 12 of the vessel.
  • the method of manufacture of the reaction vessel comprises the steps of injection moulding an inner tubular vessel 1 1 having a base 12 thicker than the walls of the vessel in cross section, and then injection moulding an outer layer 13 of an electrically conducting polymer about the inner tubular vessel 1 1 , with the outer layer 13 also having a base thicker than its wallsMoulding of the inner vessel 11 first, followed by moulding of the outer layer 13, reduces the possibility of contamination of the inner surface of vessel 11 by the outer layer material.
  • the moulding of the outer layer may cause erosion of the inner layer.
  • the inner layer is provided with thicker regions where erosion of the inner layer is expected to be worst, specifically around the base 12 of the vessel, and at the shoulder 17 where the outer layer moulding flows around the inner layer. This ensures that the outer layer material never penetrates the inner layer, hence avoiding contamination of the reaction cavity 10a by outer layer materials.
  • the outer layer also contains thicker sections in these regions, to give a low current density when heating, and hence a low heating power, avoiding undesirable heating effects.
  • the inner surface of the upper region 16 of the inner vessel 1 1 includes a flange 19 which interfits with a corresponding flange 23 on the exterior surface of lid 20 to provide a snap fit.
  • Figure 1 also illustrates a single reaction vessel receiving station 30 in a reaction apparatus in which a plurality of reaction vessels 10 are received and the reactions within monitored. It has an array of 96 receiving stations 30, four of which are illustrated in figure 2.
  • microtitre plate of standard dimensions comprises a plate 40 having reaction vessel receiving stations 41 and cooling air flow foramens 42. interspersed between each station 41.
  • the stations 41 are arranged for gripping the reaction vessels fitted therein sufficiently tightly to prevent relative movement thereof during reactions.
  • the plate 40 has side members, not shewn, which project therefrom and provide both means for maintaining the plates 40 substantially rigid and for locating the plate accurately within the reaction apparatus.
  • FIG. 1 The spatial relationship between the plate 40 carrying a reaction vessel 10 and the reaction apparatus is illustrated in figure 1 , where the microtitre plate 40 is shewn above various elements of the reaction apparatus which have functions in relation to the reaction vessels 10.
  • the temperature sensing arrangement is illustrated in figure 2.
  • This shows a foraminous pcb 50 having receiving stations 51 and temperature sensing units 52, for each receiving station 51 a temperature sensor unit 52 arranged spaced from the station.
  • each reaction vessel 10 has its temperature monitored independently of the other reaction vessels within the reaction vessel matrix. There is no contact between the sensor unit 52 and the vessel 10 and thus there is accurate and consistent temperature measurement, with no risk of cross contamination between different vessels due to transfer of vessel contents via the sensor, for example to subsequent received vessels.
  • the sensor unit 52 comprises a thermopile 53 encapsulated in a 'can' 54 with a window 55 through which a specific frequency range of radiation, from a specific field of view, may enter the can 54 to cause the thermopile to produce a signal which is then passed to temperature control means (not shewn) via the pcb 50.
  • temperature control means not shewn
  • the radiation passes through an Infra red filter (not shown) before reaching the thermopile.
  • the sensor unit 52 also includes (not shown) a local temperature sensor to provide an accurate final temperature.
  • the can 54 is provided with an aluminium aperture which blocks access of infra red radiation to the thermopile from any objects other than the specific reaction vessel that is being measured by the sensor.
  • the reaction apparatus includes a foraminous upper contact sheet 60 having a plurality of bores defining the position of a receiving station 30 and a set of foramens 61 for providing air pathways, and a foraminous lower contact sheet 70 having a set of foramens 71 for providing air pathways and having mounted upon it a plurality of electrical contact pads 72, each pad 72 aligned such that a reaction vessel 10 inserted into a station 30 will contact an underlying pad 72 for passing current through the reaction vessel 10 to heat it.
  • the upper contact sheet 60 comprises a flexible compressible sheet covered with a conducting layer, in this case a conducting fabric. This sheet is adhered by silver loaded epoxy electrically conductive adhesive to a substrate, in this case a foraminous steel sheet.
  • the upper section of the outer layer 13 overlies the shoulder 18 between the mid and upper sections of the inner vessel 11 to form an upper contact ridge 61.
  • a reaction vessel 10 is pushed through bore 30 in the upper contact sheet 60 until base of outer layer 13 comes into contact with lower contact pad 72, and upper contact ridge 13c sits against and in contact with upper contact sheet 60.
  • the foramens 61 and 71 provide ventilation and therefore ducted cooling of the reaction vessels.
  • the foramen providing the station 51 in the pcb 50 is somewhat larger than the vessel 10 and is accordingly arranged to ensure that cooling air passes close to the vessel 10 at its base and in the region of the reaction cavity 10a.
  • the voltage difference applied across each vessel can be controlled independently. In this case the voltages applied to the lower contact pads 72 are controlled independently whilst the upper contact sheet 60 is coupled to one voltage only.
  • the optical monitoring system for the reaction apparatus is illustrated in figure 3.
  • the system comprises at least one light source 80, scanning apparatus 81 , 82 for directing the light to the reaction vessels 10 in the receiving stations 30, and for receiving radiation emitted by the reaction vessels 10 and directing the radiation via a lens 83 and diffraction grating 84 to a multi-anode photomultiplier tube assembly 85 operating in a photon counting mode.
  • the mirror 81 contains a foramen at 45 degrees to the plane of the mirror, permitting laser light to pass through it to the vessels. The majority of diverging emitted light from the vessels is reflected to the diffraction grating 84, since at this point the emitted light beam is of much greater diameter than the foramen.
  • the multi-anode photomultiplier tube assembly 85 here comprises a multi-anode photomultiplier tube (MAPMT) with a 32-pixel array over which radiation from around 510 to 720 nm is dispersed. Radiation emitted by the reaction vessel contents is dispersed over the pixels of the MAPMT by the diffraction grating 84 such that the wavelength range of the radiation impinging on a photocathode of the MAPMT correlates with the position of the photocathode in the MAPMT
  • MAPMT multi-anode photomultiplier tube
  • the light source 80 is a diode pumped solid state laser (DPSS Laser) which is smaller and lighter than conventional gas lasers typically used in optical monitoring systems.
  • DPSS Laser diode pumped solid state laser
  • mirrors 82 There is a plurality of mirrors 82, or which for clarity only one is illustrated
  • the mirrors 82 are motor driven to rotate and are controlled by means (not shewn) to direct the light from the laser to any receiving station 30. Radiation emitted is returned to the foraminous mirror 81 which reflects the majority of the emitted radiation through lens 83 which focuses the radiation upon diffraction grating 84.
  • a Fresnel lens 86 is interposed between the rotatable mirrors, e.g. mirror 81 , and the receiving stations 30 to ensure that the light entering each reaction vessel 10 is substantially vertical.

Landscapes

  • Chemical & Material Sciences (AREA)
  • Health & Medical Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Physics & Mathematics (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Analytical Chemistry (AREA)
  • Biochemistry (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Physics & Mathematics (AREA)
  • Immunology (AREA)
  • Pathology (AREA)
  • Clinical Laboratory Science (AREA)
  • Spectroscopy & Molecular Physics (AREA)
  • Molecular Biology (AREA)
  • Organic Chemistry (AREA)
  • Hematology (AREA)
  • Engineering & Computer Science (AREA)
  • Plasma & Fusion (AREA)
  • Apparatus Associated With Microorganisms And Enzymes (AREA)
  • Physical Or Chemical Processes And Apparatus (AREA)
  • Investigating Or Analyzing Materials Using Thermal Means (AREA)
  • Automatic Analysis And Handling Materials Therefor (AREA)

Abstract

L'invention concerne un récipient de réaction, en général un récipient à microtitration, dans lequel sont incorporés des moyens de chauffage permettant d'effectuer la réaction, et comprenant un couvercle avec une fenêtre permettant de surveiller le contenu du récipient, cette configuration permettant également aux moyens de chauffage de garantir que la fenêtre est maintenue sans vapeur. L'appareil dans lequel sont placés lesdits récipients de réaction au cours de la réaction comprend un réseau de capteurs à thermopile servant à mesurer la température du récipient.
PCT/GB2003/005041 2002-11-19 2003-11-19 Recipients de reaction et appareil de reaction utilise avec lesdits recipients WO2004045772A2 (fr)

Priority Applications (1)

Application Number Priority Date Filing Date Title
AU2003286253A AU2003286253A1 (en) 2002-11-19 2003-11-19 Reaction vessels and reaction apparatus for use with such vessels

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
GB0226863.9 2002-11-19
GB0226863A GB0226863D0 (en) 2002-11-19 2002-11-19 Improvements in and relating to reaction vessels and reaction apparatus for use with such vessels

Publications (2)

Publication Number Publication Date
WO2004045772A2 true WO2004045772A2 (fr) 2004-06-03
WO2004045772A3 WO2004045772A3 (fr) 2004-09-16

Family

ID=9948041

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/GB2003/005041 WO2004045772A2 (fr) 2002-11-19 2003-11-19 Recipients de reaction et appareil de reaction utilise avec lesdits recipients

Country Status (3)

Country Link
AU (1) AU2003286253A1 (fr)
GB (5) GB0226863D0 (fr)
WO (1) WO2004045772A2 (fr)

Cited By (23)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
GB2404883A (en) * 2003-08-01 2005-02-16 Biogene Ltd Reaction vessels employing electroconductive coatings
WO2005118144A1 (fr) * 2004-06-04 2005-12-15 Abacus Diagnostica Oy Contrôle de la température de cuve de réaction, système avec cuve de réaction, logiciel pour système et utilisation du système
GB2435624A (en) * 2006-03-01 2007-09-05 Vapourtec Ltd Chamber Heater
GB2441833A (en) * 2006-05-26 2008-03-19 Biogene Ltd Reaction Vessel
WO2008065423A1 (fr) * 2006-11-30 2008-06-05 Enigma Diagnostics Limited Cycleur thermique
WO2009019454A1 (fr) 2007-08-03 2009-02-12 Enigma Diagnostics Limited Récipient de réaction comprenant une couche conductrice et une couche non métallique interne
WO2009030908A2 (fr) * 2007-09-06 2009-03-12 It-Is International Ltd Appareil de régulation thermique pour réactions chimiques et biochimiques
WO2010012494A1 (fr) * 2008-08-01 2010-02-04 Eppendorf Ag Appareillage d'équilibrage de la température avec possibilité d'essai, et procédé pour essayer un appareillage d'équilibrage de la température
WO2010084237A1 (fr) * 2009-01-26 2010-07-29 Wallac Oy Instrumentation et procédé de mesure optique d'échantillons
WO2010146339A1 (fr) 2009-06-15 2010-12-23 Bg Research Ltd Détection d'acides nucléiques
CN102313594A (zh) * 2011-05-18 2012-01-11 福建师范大学 不同衍射角光强分布的探测装置
US8322918B2 (en) 2008-08-01 2012-12-04 Eppendorf Ag Tempering apparatus with testing device and method for testing a tempering apparatus
US8372353B2 (en) 2007-08-03 2013-02-12 Enigma Diagnostics Limited Sample processor
WO2014143191A1 (fr) * 2013-03-13 2014-09-18 Taunk Dale Singh Capuchon de microtube
WO2015114294A1 (fr) * 2014-01-29 2015-08-06 Bg Research Ltd Identification d'agents pathogènes sur le terrain
CN105263627A (zh) * 2013-01-18 2016-01-20 生米公司 分析设备
WO2016091344A3 (fr) * 2014-12-10 2016-08-04 Fraunhofer-Gesellschaft zur Förderung der angewandten Forschung e.V. Corps de régulation de température pour plaque multipuits et procédé et dispositif pour congeler et/ou décongeler des échantillons biologiques
CN107041129A (zh) * 2014-12-12 2017-08-11 微量热技术有限公司 用于以无密封的方式对毛细管调温的系统和方法
CN108085246A (zh) * 2011-03-25 2018-05-29 娴熟的解决方案公司 用于一次性生物反应器的复合传感器组件
WO2019071232A1 (fr) * 2017-10-06 2019-04-11 Wyatt Technology Corporation Procédé et appareil permettant d'atténuer l'évaporation dans des mesures à haut débit
US11767552B2 (en) 2019-03-21 2023-09-26 Biomeme, Inc. Multi-function analytic devices
US11827875B2 (en) 2006-08-02 2023-11-28 Finesse Solutions, Inc. Method for manufacturing a composite sensor
US11892461B1 (en) 2020-09-18 2024-02-06 Biomeme, Inc. Portable devices and methods for analyzing samples

Families Citing this family (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
GB2431006A (en) * 2005-09-12 2007-04-11 Polylogic Ltd Data capture system for microtiter plates
GB2457094A (en) * 2008-02-04 2009-08-05 Univ Dublin City A cuvette assembly for holding milking samples
EP3385720B1 (fr) * 2017-04-05 2020-09-02 F. Hoffmann-La Roche AG Support de récipient destiné à un système d'analyte automatisé
WO2023274859A1 (fr) * 2021-06-29 2023-01-05 Signify Holding B.V. Ensemble photoréacteur

Citations (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5106540A (en) * 1986-01-14 1992-04-21 Raychem Corporation Conductive polymer composition
US5167929A (en) * 1988-07-07 1992-12-01 Walter Sarstedt Geraete Und Verbrauchsmaterial Fuer Medizin Und Wissenshaft Reaction vessel for receiving minimal quantities of fluid samples
US5710381A (en) * 1990-11-29 1998-01-20 The Perkin-Elmer Corporation Two piece holder for PCR sample tubes
GB2333250A (en) * 1998-01-16 1999-07-21 Secr Defence Reduced volume heated reaction vessel
WO2001066254A1 (fr) * 2000-03-08 2001-09-13 The Secretary Of State For Defence Systeme reactionnel permettant d'obtenir des cycles thermiques
US20020028165A1 (en) * 1996-12-06 2002-03-07 Martin A Lee Reaction vessels
US20020055187A1 (en) * 2000-11-03 2002-05-09 Rainer Treptow Method and apparatus for tempering specimens

Family Cites Families (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6469311B1 (en) * 1997-07-16 2002-10-22 Molecular Devices Corporation Detection device for light transmitted from a sensed volume
WO2001004608A1 (fr) * 1999-07-07 2001-01-18 Ljl Biosystems, Inc. Dispositif de detection optique
US6106784A (en) * 1997-09-26 2000-08-22 Applied Chemical & Engineering Systems, Inc. Thawing station
US5851492A (en) * 1997-09-30 1998-12-22 Blattner; Frederick R. Microtiter plate sealing system
US6306658B1 (en) * 1998-08-13 2001-10-23 Symyx Technologies Parallel reactor with internal sensing
WO2002041999A1 (fr) * 2000-11-24 2002-05-30 Novo Nordisk A/S Systeme de decondensation
WO2002047821A1 (fr) * 2000-12-12 2002-06-20 3-Dimensional Pharmaceuticals, Inc. Plaque de microtitrage a dispositif de chauffage integre

Patent Citations (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5106540A (en) * 1986-01-14 1992-04-21 Raychem Corporation Conductive polymer composition
US5167929A (en) * 1988-07-07 1992-12-01 Walter Sarstedt Geraete Und Verbrauchsmaterial Fuer Medizin Und Wissenshaft Reaction vessel for receiving minimal quantities of fluid samples
US5710381A (en) * 1990-11-29 1998-01-20 The Perkin-Elmer Corporation Two piece holder for PCR sample tubes
US20020028165A1 (en) * 1996-12-06 2002-03-07 Martin A Lee Reaction vessels
GB2333250A (en) * 1998-01-16 1999-07-21 Secr Defence Reduced volume heated reaction vessel
WO2001066254A1 (fr) * 2000-03-08 2001-09-13 The Secretary Of State For Defence Systeme reactionnel permettant d'obtenir des cycles thermiques
US20020055187A1 (en) * 2000-11-03 2002-05-09 Rainer Treptow Method and apparatus for tempering specimens

Cited By (42)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
GB2404883B (en) * 2003-08-01 2008-02-27 Biogene Ltd Improvement in biological, chemical and biochemical processes and apparatus
GB2404883A (en) * 2003-08-01 2005-02-16 Biogene Ltd Reaction vessels employing electroconductive coatings
US7754473B2 (en) 2004-06-04 2010-07-13 Abacus Diagnostica Oy Temperature control of reaction vessel, system with reaction vessel, software product for system and use of system
WO2005118144A1 (fr) * 2004-06-04 2005-12-15 Abacus Diagnostica Oy Contrôle de la température de cuve de réaction, système avec cuve de réaction, logiciel pour système et utilisation du système
GB2435624A (en) * 2006-03-01 2007-09-05 Vapourtec Ltd Chamber Heater
GB2435624B (en) * 2006-03-01 2009-05-27 Vapourtec Ltd Chamber heater
GB2441833A (en) * 2006-05-26 2008-03-19 Biogene Ltd Reaction Vessel
GB2441833B (en) * 2006-05-26 2011-08-10 Biogene Ltd Reaction Vessel & Apparatus
US11060055B2 (en) 2006-08-02 2021-07-13 Finesse Solutions, Inc. Composite sensor assemblies for single use bioreactors
US11827875B2 (en) 2006-08-02 2023-11-28 Finesse Solutions, Inc. Method for manufacturing a composite sensor
WO2008065423A1 (fr) * 2006-11-30 2008-06-05 Enigma Diagnostics Limited Cycleur thermique
US8372353B2 (en) 2007-08-03 2013-02-12 Enigma Diagnostics Limited Sample processor
WO2009019454A1 (fr) 2007-08-03 2009-02-12 Enigma Diagnostics Limited Récipient de réaction comprenant une couche conductrice et une couche non métallique interne
US9138748B2 (en) 2007-08-03 2015-09-22 Enigma Diagnostics Limited Reaction vessel comprising conductive layer and inner non-metallic layer
WO2009030908A3 (fr) * 2007-09-06 2009-08-13 It Is Internat Ltd Appareil de régulation thermique pour réactions chimiques et biochimiques
WO2009030908A2 (fr) * 2007-09-06 2009-03-12 It-Is International Ltd Appareil de régulation thermique pour réactions chimiques et biochimiques
US9492825B2 (en) 2007-09-06 2016-11-15 It-Is International Limited Thermal control apparatus for chemical and biochemical reactions
EP2153901A1 (fr) * 2008-08-01 2010-02-17 Eppendorf Ag Dispositif d'équilibrage de la température avec la possibilité de tester et procédé de test d'un dispositif d'équilibrage de la température
WO2010012494A1 (fr) * 2008-08-01 2010-02-04 Eppendorf Ag Appareillage d'équilibrage de la température avec possibilité d'essai, et procédé pour essayer un appareillage d'équilibrage de la température
US8322918B2 (en) 2008-08-01 2012-12-04 Eppendorf Ag Tempering apparatus with testing device and method for testing a tempering apparatus
WO2010084237A1 (fr) * 2009-01-26 2010-07-29 Wallac Oy Instrumentation et procédé de mesure optique d'échantillons
US8814427B2 (en) 2009-01-26 2014-08-26 Wallac Oy Instrumentation and method for optical measurement of samples
WO2010146339A1 (fr) 2009-06-15 2010-12-23 Bg Research Ltd Détection d'acides nucléiques
CN108085246A (zh) * 2011-03-25 2018-05-29 娴熟的解决方案公司 用于一次性生物反应器的复合传感器组件
CN108085246B (zh) * 2011-03-25 2021-11-09 娴熟的解决方案公司 用于一次性生物反应器的复合传感器组件
CN102313594A (zh) * 2011-05-18 2012-01-11 福建师范大学 不同衍射角光强分布的探测装置
US10457983B2 (en) 2013-01-18 2019-10-29 B Iomeme, Inc. Analytic device
EP2945742A4 (fr) * 2013-01-18 2016-09-21 Biomeme Inc Dispositif analytique
CN105263627A (zh) * 2013-01-18 2016-01-20 生米公司 分析设备
US9579655B2 (en) 2013-01-18 2017-02-28 Biomeme Incorporated Analytic device
US11667963B2 (en) 2013-01-18 2023-06-06 Biomeme, Inc. Analytic device
WO2014143191A1 (fr) * 2013-03-13 2014-09-18 Taunk Dale Singh Capuchon de microtube
WO2015114294A1 (fr) * 2014-01-29 2015-08-06 Bg Research Ltd Identification d'agents pathogènes sur le terrain
CN107257710B (zh) * 2014-12-10 2020-07-31 弗劳恩霍夫应用研究促进协会 用于多孔板的温度控制体及用于冷冻和/或解冻生物样本的方法和设备
US10987673B2 (en) 2014-12-10 2021-04-27 Fraunhofer-Gesellschaft Zur Foerderung Der Angewandten Forschung E. V. Temperature-control element for a multiwell plate and method and device for freezing and/or thawing biological samples
WO2016091344A3 (fr) * 2014-12-10 2016-08-04 Fraunhofer-Gesellschaft zur Förderung der angewandten Forschung e.V. Corps de régulation de température pour plaque multipuits et procédé et dispositif pour congeler et/ou décongeler des échantillons biologiques
CN107257710A (zh) * 2014-12-10 2017-10-17 弗劳恩霍夫应用研究促进协会 用于多孔板的温度控制体及用于冷冻和/或解冻生物样本的方法和设备
CN107041129B (zh) * 2014-12-12 2020-04-17 微量热技术有限公司 用于以无密封的方式对毛细管调温的系统和方法
CN107041129A (zh) * 2014-12-12 2017-08-11 微量热技术有限公司 用于以无密封的方式对毛细管调温的系统和方法
WO2019071232A1 (fr) * 2017-10-06 2019-04-11 Wyatt Technology Corporation Procédé et appareil permettant d'atténuer l'évaporation dans des mesures à haut débit
US11767552B2 (en) 2019-03-21 2023-09-26 Biomeme, Inc. Multi-function analytic devices
US11892461B1 (en) 2020-09-18 2024-02-06 Biomeme, Inc. Portable devices and methods for analyzing samples

Also Published As

Publication number Publication date
GB2424381A (en) 2006-09-27
GB2424199A (en) 2006-09-20
GB0609750D0 (en) 2006-06-28
AU2003286253A1 (en) 2004-06-15
WO2004045772A3 (fr) 2004-09-16
GB0612553D0 (en) 2006-08-02
GB2424380B (en) 2007-06-27
GB2424381B (en) 2007-06-27
GB0226863D0 (en) 2002-12-24
GB2424380A (en) 2006-09-27
GB0612554D0 (en) 2006-08-02
GB2424199B (en) 2007-06-27
GB2404882A (en) 2005-02-16
AU2003286253A8 (en) 2004-06-15
GB0326878D0 (en) 2003-12-24

Similar Documents

Publication Publication Date Title
WO2004045772A2 (fr) Recipients de reaction et appareil de reaction utilise avec lesdits recipients
WO2007138302A1 (fr) problÈmes de performances dans l'utilisation de rÉcipients pour des applications biologiques
US8597937B2 (en) Reaction apparatus
EP2898952B1 (fr) Dispositif de réalisation de réactions chimiques ou biologiques
EP2555873B1 (fr) Système de réactions biochimiques
US20190224684A1 (en) Apparatus and method for segmented thermal cycler
US9180459B2 (en) Devices and methods for thermally-mediated chemical reactions
US9089828B2 (en) Optical system for chemical and/or biochemical reactions
WO2008107683A2 (fr) Appareil et procédé de cyclage thermique
US7670834B2 (en) Gas thermal cycler
EP3126052B1 (fr) Système de réaction biochimique
US9121057B2 (en) Cartridge and device for analyzing biological samples using temperature-controlled biological reactions
US20030102221A1 (en) Multi-capillary electrophoresis apparatus
WO2008035074A2 (fr) Améliorations à un appareil de réaction
US20070194247A1 (en) Compact optical module for fluorescence excitation and detection
US20110136109A1 (en) System And Method For Cycling Liquid Samples Through A Series Of Temperature Excursions
WO2004024330A2 (fr) Appareil de commande
WO2005011834A2 (fr) Ameliorations apportees a des cuves de reaction
WO2010010361A1 (fr) Améliorations dans un appareil réacteur

Legal Events

Date Code Title Description
AK Designated states

Kind code of ref document: A2

Designated state(s): AE AG AL AM AT AU AZ BA BB BG BR BY BZ CA CH CN CO CR CU CZ DE DK DM DZ EC EE ES FI GB GD GE GH GM HR HU ID IL IN IS JP KE KG KP KR KZ LC LK LR LS LT LU LV MA MD MG MK MN MW MX MZ NI NO NZ OM PG PH PL PT RO RU SC SD SE SG SK SL SY TJ TM TN TR TT TZ UA UG US UZ VC VN YU ZA ZM ZW

AL Designated countries for regional patents

Kind code of ref document: A2

Designated state(s): BW GH GM KE LS MW MZ SD SL SZ TZ UG ZM ZW AM AZ BY KG KZ MD RU TJ TM AT BE BG CH CY CZ DE DK EE ES FI FR GB GR HU IE IT LU MC NL PT RO SE SI SK TR BF BJ CF CG CI CM GA GN GQ GW ML MR NE SN TD TG

121 Ep: the epo has been informed by wipo that ep was designated in this application
122 Ep: pct application non-entry in european phase
NENP Non-entry into the national phase in:

Ref country code: JP

WWW Wipo information: withdrawn in national office

Country of ref document: JP