WO2012063011A2 - Chauffage et refroidissement de cuves à réaction biologique à faible volume - Google Patents

Chauffage et refroidissement de cuves à réaction biologique à faible volume Download PDF

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Publication number
WO2012063011A2
WO2012063011A2 PCT/GB2011/001565 GB2011001565W WO2012063011A2 WO 2012063011 A2 WO2012063011 A2 WO 2012063011A2 GB 2011001565 W GB2011001565 W GB 2011001565W WO 2012063011 A2 WO2012063011 A2 WO 2012063011A2
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WO
WIPO (PCT)
Prior art keywords
vessel
cup assembly
assembly
cooling
reaction
Prior art date
Application number
PCT/GB2011/001565
Other languages
English (en)
Other versions
WO2012063011A3 (fr
Inventor
Nelson Nazareth
Antony Driscoll
David Edge
Original Assignee
Bg Research Ltd
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
Priority claimed from GBGB1018794.6A external-priority patent/GB201018794D0/en
Priority claimed from GBGB1100625.1A external-priority patent/GB201100625D0/en
Application filed by Bg Research Ltd filed Critical Bg Research Ltd
Priority to GB1308226.8A priority Critical patent/GB2501011A/en
Priority to US13/261,654 priority patent/US20150144299A1/en
Priority to EP11796763.8A priority patent/EP2637789A2/fr
Priority to JP2013537198A priority patent/JP5892709B2/ja
Priority to CN201180060968.8A priority patent/CN103260760B/zh
Publication of WO2012063011A2 publication Critical patent/WO2012063011A2/fr
Publication of WO2012063011A3 publication Critical patent/WO2012063011A3/fr

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Classifications

    • F—MECHANICAL ENGINEERING; LIGHTING; HEATING; WEAPONS; BLASTING
    • F25—REFRIGERATION OR COOLING; COMBINED HEATING AND REFRIGERATION SYSTEMS; HEAT PUMP SYSTEMS; MANUFACTURE OR STORAGE OF ICE; LIQUEFACTION SOLIDIFICATION OF GASES
    • F25B—REFRIGERATION MACHINES, PLANTS OR SYSTEMS; COMBINED HEATING AND REFRIGERATION SYSTEMS; HEAT PUMP SYSTEMS
    • F25B21/00—Machines, plants or systems, using electric or magnetic effects
    • F25B21/02—Machines, plants or systems, using electric or magnetic effects using Peltier effect; using Nernst-Ettinghausen effect
    • 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
    • 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
    • B01L9/06—Test-tube stands; Test-tube holders
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B65—CONVEYING; PACKING; STORING; HANDLING THIN OR FILAMENTARY MATERIAL
    • B65D—CONTAINERS FOR STORAGE OR TRANSPORT OF ARTICLES OR MATERIALS, e.g. BAGS, BARRELS, BOTTLES, BOXES, CANS, CARTONS, CRATES, DRUMS, JARS, TANKS, HOPPERS, FORWARDING CONTAINERS; ACCESSORIES, CLOSURES, OR FITTINGS THEREFOR; PACKAGING ELEMENTS; PACKAGES
    • B65D81/00—Containers, packaging elements, or packages, for contents presenting particular transport or storage problems, or adapted to be used for non-packaging purposes after removal of contents
    • B65D81/38—Containers, packaging elements, or packages, for contents presenting particular transport or storage problems, or adapted to be used for non-packaging purposes after removal of contents with thermal insulation
    • 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
    • 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
    • B01L2300/0832—Geometry, shape and general structure cylindrical, tube shaped
    • 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
    • B01L2300/1822—Conductive heating, heat from thermostatted solids is conducted to receptacles, e.g. heating plates, blocks using Peltier elements
    • 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
    • B01L2300/00—Additional constructional details
    • B01L2300/18—Means for temperature control
    • B01L2300/1894—Cooling means; Cryo cooling

Definitions

  • the invention relates to apparatus for biological or chemical reactions where thermal cycling is employed in the reaction. It is particularly concerned with reactions such as polymerase chain reactions (PCR), although isothermal reactions will also be quite possible.
  • PCR polymerase chain reactions
  • 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 8 X 1 2 array.
  • the apparatus includes means to monitor the temperature and to control the heating power applied to the reaction vessel contents.
  • the cooling part of the cycle may be effected using water or non-electrically conducting fluids like 'Fluid XP' or a cooling block, powered by peltier devices, and/or a fan blowing cooled air over the vessei or vessels.
  • the cooling is continuously present and the heating part of the cycle is carried out against a background of the constant cooling
  • heating is effected using a direct heater eg thermal mats and cooling by either forced air or actively by thermo electric heat pumps.
  • heating and cooling are effected by shuttling between blown hot air and blown cold air.
  • a block based system will inevitably have a relatively high thermal mass while a forced air system will have a low thermal mass. This can militate against rapid heating and cooling.
  • apparatus performing thermal cycling with 96 vessel arrays may be arranged to offer the vessel arrays to apparatus vessel stations for the cycling, and on completion thereof to remove them.
  • the thermal cycle will be the most efficiently and rapidly effected the more intimate is the contact between each vessel and the heating and cooling systems the more likely is there to be a mechanical fatigue issue for the vessel stations, wrought by constant repeated emplacement and withdrawal of vessels, exacerbated by the thermal cycling. Disintegration of one or more vessel stations may thus occur. The replacement of the components of the vessel receiving station can be a costly exercise.
  • the present invention provides apparatus wherein thermal cycling in biological or chemical reactions is maintained at a desirable rate whilst at the same time the integrity of each vessel station is maintained for at least an acceptable period of use.
  • a further consideration for rapid detection of DNA species, such as pathogens, is the ability to accurately test for multiple species in a single test within a minimum timeframe.
  • Apparatus capable of independent control and monitoring of each vessel in for example a 96n vessel array would allow multiple tests to be completed simultaneously, thus in itself providing a relatively short timeframe, whilst also conferring the important benefit of greater veracity due to the independent monitoring ability.
  • Such a system would then be capable of completing the PCR process in under 20 minutes, for a commonly accepted 3 step, 30 cycle protocol (zero seconds at 95°C, one second at 55°C and five seconds at 72°C - as an example) and is therefore highly suited to rapid detection of pathogens. Additionally it would be highly advantageous for such technology to be applied to any number of vessels and also to be used portably at the point of care.
  • standard i 96 vessel thermal cyclers of modern design and construction can cycle at average speeds of up to one and a half degrees Celsius per second in the liquid using standard consumables.
  • Reduction in the energy requirements of the thermal cycling process is also a pre-requisite for thermal cycling at rates exceeding 5°C/s in the fluid.
  • a thermal storage system as demonstrated for example in US12/381 ,953 can reduce the energy requirements for such thermal cycling apparatus.
  • the apparatus therein described is unable to drive the vessel to a temperature below that allowed by the Dt max of the attached thermoelectric cooler (TEC).
  • TEC thermoelectric cooler
  • the heat removal module described in that document of necessity operated at temperatures above the required lowest temperature so that a high cooling rate could not be achieved.
  • varying thermal diffusion rates across the block are possible as the outside edges may lose more temperature to ambient for example. This could be compensated for by the control electronics, but with greater thermal cycling rates the problem is potentially exacerbated.
  • the present invention provides apparatus wherein thermal cycling in biological or chemical reactions is performed at cycling rates greatly above those achievable by existing technology and wherein each reaction vessel is controlled independently.
  • a vessel cup assembly for receiving a chemical and/or biological reaction process vessel containing reactants and processing the reaction therein and the vessel cup assembly comprising:
  • a chemical and/or biological reaction apparatus arranged for the reception of a vessel cup assembly as set forth above.
  • a chemical and/or biological reaction process utilising the vessel cup assembly and the apparatus set for above.
  • the vessel cup assembly may be of integral construction.
  • the cooling portion may be constructed as an anchor member to anchor the assembly into a reaction vessel receiving station in a cooler assembly in or for a chemical and/or biological reaction apparatus.
  • the reaction vessel receiving portion may comprise a cup for receiving snugly a reaction vessel.
  • a snug reception of a reaction vessel into a vessel cup implies both substantial contiguity and separability.
  • the heater portion may at least partially overlap the reaction vessel and be surrounded by a heater which may be in the form of a wire coil wound thereupon.
  • the coil may be encased in a paint, such as an enamel paint, which can be 'cooked' to stabilise the coil and insulate it exteriorly.
  • a glue such as an ultra-violet curable glue, is employed which also has the property of retaining the wire in place.
  • the wire may be nickel chrome 0.21 mm diameter driven with a voltage of 24 volts and capable of drawing a maximum current of 2.2 amps.
  • the length of the wire in the context of the microtitre vessel having a capillary reaction chamber as herein proposed, is of the order of 36cm. Other reaction vessels will likely have different requirements.
  • the heater may be a sheath of electrically conductive polymer (ecp) (comprising electrically conductive particles such as graphite or metal or similar in an inert plastic carrier such as polypropylene or similar) or of metal film.
  • ecp electrically conductive polymer
  • inert plastic carrier such as polypropylene or similar
  • the vessel receiving portion may have a constant wall thickness so as to avoid hotspots - temperature variation along the length thereof or therearound.
  • a cup wall which tapers down towards the open end provides an effective control to the flow and even distribution of heat whilst also facilitating installation, snug fitting and removal of a mating reaction vessel.
  • the cup entry wall thickness is of the order of 0.35 to 0.45, preferably 0.4 mm and the cup base wall thickness is of the order of 0.9 to 1 .1 , preferably 0.95mm
  • the wall thickness is sufficient at a convenient intermediate station along the length of the cup for the formation of a temperature sensor receiving recess.
  • a thermal sensor such as a thermistor, for thermal control.
  • Measurement Specialties Ltd have supplied a suitable bare thermistor having a length under 3mm and a mean diameter of the order of 0.2mm.
  • the tail wire may be wound around the vessel receiving portion a couple of times.
  • the thermistor is preferably located a short distance above the heater so as not to read heater temperature but the temperature of the cup. In this way the thermistor can be arranged or calibrated to operate in a predictive mode, that is it can indicate that the temperature of the reactants will be such and such at a known number of milliseconds later.
  • a vessel cup assembly as herein set forth has the peculiar advantage that when the heater portion heats up and heat necessarily flows both downwards and upwards, the downward flow acts as a barrier to the operation of the cooler portion whilst the vessel receiving portion is in heating mode.
  • the sensor should ideally be positioned such that its physical temperature exactly matches that of the reagent fluids, and secondly be constructed such that it imposes a reproducible and calculable thermal lag commensurate with that experienced by the fluid itself.
  • the overaii dimensions of a vessel cup assembly in accordance with the invention are of the order of 2 to 4 cm long by 0.4 to 0.7 mm diameter. Effectively the bulk of the vessel cup assembly being quite small heat can be inputted and removed very quickly, that is the ramping rates can be practically as high as the reaction can accept.
  • a vessel cup assembly formed for example of machinable aluminium alloy the above dimensions are sufficient for repeated insertion and withdrawal of a reaction vessel. Copper or silver may be used in place of aluminium but the latter is particularly suitable being inexpensive, readily machinable and receptive of anodisation . Anodisation reduces the possibility of shorting across the coil and inhibits corrosion. Where the vessel cup assembly thus comprises a conductive core this latter may constitute the return path for electrical power to the heater.
  • the vessel receiving portion and the heater portion comprise a right cylinder, and are formed from a rod, thus facilitating manufacture and the winding of the heating coil where such is used.
  • the heater portion has an external screw-thread-like groove for seating the wire. This both facilitates emplacement and retention of the coil and increases the surface areas of the heater portion and the wire which contact each other.
  • the thread profile is rounded to match the wire profile, a V thread profile has been found acceptable. Insofar as the wire has no insulative coating and the heater portion is insulated, for example by anodisation, then the thread profile will be such that adjacent coils of wire do not touch one another.
  • a method of forming the vessel cup assembly may accordingly comprise: taking a metal, preferably aluminium rod of appropriate dimensions;
  • the glue may be applied as a spot at the beginning and end of the wire.
  • a heat insulative glue or jacket may be applied to the coil assembly and cured subsequently.
  • the manufacturing process may be assisted by retaining a spigot below the designated cooler portion of the assembly by which spigot the rod may be held for the drilling, turning, milling if required, gluing and wire winding and curing steps, the spigot then being removed. If the cooling portion is to project into the coolant then the spigot may constitute the projecting member or, if fins are to be formed on the projecting member the spigot may be below the projecting member for subsequent removal.
  • the manufacturing process includes the step of turning a rod of the outside diameter of the stop flange down at the cup receptor, heater, and cooler portions.
  • the heat transfer portion may accordingly comprise a pin which will protrude into a cooling liquid channel in the cooling assembly.
  • the pin may be perforated or ribbed so as to maximise the heat transfer surface thereof. If the pin has a transverse hole for the passage of cooling fluid then the vessel cup assembly may incorporate an indicator, if not a keyway, wherewith to ensure alignment. The intrusion of the pin into the cooling fluid passage, in conjunction with the liquid flow rate is advisedly such that, where several such pins intrude in series array the liquid temperature is substantially the same at each.
  • the cooler portion is preferably formed to be an interference and sealing fit in the intended cooling assembly and may accordingly incorporate the above mentioned annular anchor stop for ensuring correct insertion thereof into a cooling assembly.
  • the arrangement is accordingly preferably such that the vessel cup assembly may be pressed into a cooling assembly, perhaps employing a mandrel shaped to engage the interior base of the vessel receiving portion.
  • the interference fit of course assists heat transfer by conduction.
  • the cooling portion and the cooling assembly are formed from the same material, preferably machinable aluminium.
  • expansion and contraction due to heat should not affect the fit, which preferably remains continuous around and beneath the cooling portion, in other words with the cooling portion not contacting the cooling fluid except insofar as a hole may be formed in the cooling assembly to allow air to bleed from between the cooling portion and the cooling assembly.
  • the air bleed hole may be blind and formed either upwards in the cooling portion or downwards in the cooling assembly.
  • the cooling assembly may comprise a matrix having therein a channel adapted for the flow of a coolant liquid.
  • the matrix may be formed from subassemblies arranged to mate at a half channel plane.
  • the channel will be labyrinthine and serpentine.
  • cooling assembly For the context of a cooling assembly whose cooling liquid contacts the cooling portion the fitment of the vessel station it is even more important for the assembly of cooling portion to cooling assembly to be in a sealed manner. It is also advantageous that replaceable sealing devices such as O-rings and sealing gels are avoided thus minimising cost and complexity and so that their emplacement cannot be forgotten.
  • the cooling assembly may be accordingly constructed from polypropylene, resin or other such flexible material and is preferably, in the case of a 96 well array, a single block. It should be noted that the pin assembly need not intrude into the liquid channel, the passage of the fluid through the block itself being able to remove the excess thermal energy at the required rate.
  • apparatus for effecting such reactions and incorporating a cooling assembly according to the invention may also have a heater for heating the coolant to the desired temperature. This has the added advantage of preventing condensation from forming on the exterior of the module.
  • Cooling of these assemblies may therefore be provided by a liquid coolant, which in the preferred embodiment is a non-charge carrying fluid such as Fluid XP.
  • a liquid coolant which in the preferred embodiment is a non-charge carrying fluid such as Fluid XP.
  • the fluid may be arranged into a circuit incorporating a radiator whereby excess heat can be vented to atmosphere.
  • this radiator may be controlled so that only the required amount of heat is removed and then this fluid is returned to a reservoir.
  • the temperature of the fluid entering the block is typically arranged, via a heat exchanger, to be of the order of 20 to 40°C preferably room temperature, ie around 25°C.
  • the temperature can in fact also be any below the lowest in the cycle; however a higher temperature reduces the energy requirements generally.
  • thermal cycling is performed via means of increasing current to the heating coil wrapped intimately around the vessel receiving portion and that this is against the constant cooling of the liquid.
  • the power is removed from the heater and the rod will very rapidly drop to the temperature of the coolant fluid.
  • the temperature sensor inserted immediately below the reaction chamber is used to control how much current is required to be supplied to the coil. It is an important feature of the construction of a preferred embodiment of the invention that heat from the heater spreads both downwards and upwards at given and controlled rates with the result that a thermal blanket is formed above the cooling portion whilst heat is permeating uniformly upward into the vessel receiving portion and thence into the reaction vessel.
  • an important advantage of the invention may lie in the removability and replaceability of the vessel cup assembly in relation to the cooling assembly.
  • an insertion tool may be provided for driving a vessel cup assembly home in the cooling assembly.
  • a failed assembly may be removed with a suitable gripping device such as pliers or, more likely, by drilling through the failed vessel cup assembly.
  • the cooling assembly may incorporate a manifold or mount for contacts such as those for electrical supply to the heater and for the thermal sensor.
  • the manifold or mount may conveniently comprise a printed circuit board (PCB).
  • the apparatus may be of a type employing a single station - for a single reaction vessel.
  • the apparatus may be of the type employing a multiplicity of stations.
  • the apparatus may be arranged to receive in stations a standard array of 96, or an integer multiple thereof, microtitre reaction vessels in a rectangular array, usually comprising 12 x 8 such stations.
  • the apparatus may be a thermocycling apparatus for performing, for example, polymerase chain reactions (PCR).
  • the reaction vessel as such for the 96n array context is typically a microtitre vessel of by now somewhat standard construction.
  • the vessel having overall dimensions of the order of 2cm long and 0.7cm maximum diameter, has a reaction portion which tapers down from about 0.45cm to about 0.3cm and a funnel entry portion for accepting a transparent lid.
  • the vessel is sealed with a cap for the duration of a reaction and such a cap may be translucent or even transparent for at least a part thereof adjacent the sample whereby the progress of the reaction can be monitored by an optical system external to the reaction vessel.
  • the reaction vessel may be formed of a plastic loaded with carbon particles for thermal conductivity.
  • reaction vessel may be formed simply of polypropylene, indeed moulded as a 12 X 8 well block. This is considerably cheaper of manufacture than the individual, carbon loaded well above described and a PCR process conducted with it will be somewhat longer than the 20 minutes. This of course implies a bank of 96 vessel cup assemblies. It will be appreciated that these assemblies will be rooted in a cooling assembly; also that this can be the case for individually formed reaction vessels as above described. These latter are usually mounted in a preformed tray.
  • the vessel cup assembly cooling portion may be arranged for attachment to a TEC or Peltier cell.
  • the cooling portion may be of frusto-conical shape, with a broad base which can be soldered to the face of the TEC.
  • a low temperature indium based solder is preferred which will be adhered to a TEC face in a vapour phase oven to achieve an even temperature distribution across the base.
  • the TEC can be rendered inert during the heating part of the cycle so that very little heat goes other than into the cup.
  • the cooling portion may comprise a pedestal of a metal such as copper attached to the aluminium, for example by swaging, thereafter to the TEC by soldering.
  • An alternative is to have a mechanical frame to hold the vessels onto the TECs or to screw the copper to the aluminium.
  • each of the vessels may have its own individual heat removal module, with masses and construction optimised to further reduce energy requirements of thermal cycling.
  • These modules may be entirely independent of each other but arranged so that several may be ganged for an identical reaction process as required.
  • Discrete elements can also constitute an array of up to either 4 or to 16 vessels, this being a two by two or four by four array. This arrangement has the further advantage that elements can be removed individually for routine maintenance purposes.
  • a single vessel cycling unit may use an 8mm by 8mm TEC device, the 4 and 16 vessels using devices with dimensions of 17mm by 17mm and 35mm by 35mm respectively.
  • a TEC While use of a TEC in this way can greatly increase the cooling rates achievable by this system it may concurrently reduce the ability of the system to heat rapidly This problem can be overcome by the provision of a second heating circuit connected in series with the peltier elements allowing additional heating to be supplied to the system as and when required.
  • the additional heating circuit may be printed onto the top of the TEC device or indeed sandwiched between 2 ceramic plates acting as the top surface of the TEC.
  • the TECs in particular may be prone to failure.
  • Materials possessing a high modulus of elasticity may be particularly useful to minimise the effects of thermally induced mechanical stress.
  • the top and bottom surfaces of the TEC may accordingly be attached using Indium based solders or other such materials possessing high thermal conductivity and a high modulus of elasticity.
  • the preferred construction method is an indium based solder to both surfaces of the TEC with the assembly constructed in a vapour phase oven using a gallium based liquid whose temperature can be controlled to reach the liquidus point of the solder.
  • To facilitate this TEC devices should preferably be "metallised” by pre-tinning to provide a surface capable of keying the indium based solder to.
  • the entire assembly or any of its component parts can be covered in a conformal coating, preferably parylene in order to prevent failure due to atmospheric conditions, in particular condensation of water which could cause shorts in the TEC pillars and or corrosion/cracks during thermal changes.
  • a conformal coating preferably parylene in order to prevent failure due to atmospheric conditions, in particular condensation of water which could cause shorts in the TEC pillars and or corrosion/cracks during thermal changes.
  • the mould for the reaction vessels might therefore be highly polished as well as the interior surface of the reaction vessel receiving portion.
  • a ramp rate in excess of 5°C/s can be achieved with a reaction vessel wall thickness below 0.3mm, bearing in mind construction techniques known in the art such as plastic moulding, and constructed of a material possessing thermal conductivity of minimally 1 W/MK.
  • the vessels are formed of highly loaded polypropylene containing 60% carbon w/v and with a wall thickness of 0.2mm.
  • the entirety of the reactant fluid column is preferably encapsulated in the vessel holder portion.
  • the cups themselves may be gold plated for optimum performance. This and the elasticity provided by Indium solder reduces failure rates of the component parts of the cycling system.
  • a further level of control can be provided by the addition of an independently controlled heated compression ring at the top of the apparatus, this provides two functions. Firstly, it ensures that the vessel is compressed into the tapered fitting ensuring thermal contact and secondly it provides means to add additional heat, whether to ensure no condensation can form on the lid of the tube or to prevent thermal gradients forming when larger volumes such as over 100 ⁇ are used in the apparatus
  • An additional diode sensor may be built into the centre of each TEC to facilitate temperature measurement and control.
  • the apparatus employs electronic control circuits capable of individually addressing each of the vessels and controlling them at the desired ramping to achieve temperature accuracies of less than +/- 0.5, possibly even 0.2°C.
  • the control gear can incorporate diodes in its circuitry arranged so as to provide feedback on the thermal performance of the TEC devices, for example to determine if a failure has occurred and assess whether minimum requirements for heating/cooling power are being met by every TEC device in the array.
  • the TEC uses a larger base ceramic arranged for mounting 2, 4, 8, 16 or more individual die sets thereupon, each TEC die set having its own isolated upper ceramic plate separate from its adjacent TEC.
  • the TECs thus form an easily locatable group that can be mounted more accurately than individual TECs.
  • Each TEC keeps its own individual thermal profile.
  • Wires for connections can be either threaded through holes in the lower ceramic base plate or through vias formed using PCB through hole plating techniques. This enables compression and solder fixing to a sub assembly that provides both electrical and thermal connection. If a requirement for additional heating exists then these TEC devices may similarly be modified by constructing a TEC using an additional top ceramic tile incorporating a heating element. The two top tiles can then be bonded together in a sand wedge so that the heating element is protected between the ceramic sand wedge. The heating element can be etched or silk screen printed on to the surface of the ceramic.
  • this larger TEC device can incorporate an additional top ceramic tile incorporating a temperature measurement element, the two top tiles forming a sand wedge that encapsulates a temperature measurement element such as a thermistor or diode junction. This can provide temperature feedback on the operation of the TEC itself including indicating failure.
  • HRM heat transfer module
  • it is preferably individual to a unique reaction vessel or at most to a small group thereof, such as an array of four. In this way, particularly in the 96n vessel context, cooling of a particular vessel or group of vessels occurs in parallel with that of another vessel or group and is consequently somewhat more consistent and perhaps quicker than if a larger group were cooled in series by a single heat reduction module.
  • a suitable heat transfer module may comprise a jacket having cooling liquid (water) inlet and outlet, and a core fitting within the jacket, the core having a rugose, ridged or finned surface to a cooling liquid chamber therearound.
  • the jacket may resemble a waffle, having a plurality of cooling liquid inlets, one per vessel or small group of vessels, and one or more liquid outlet manifolds.
  • the core may resemble a bolt with a cylindrical shank and, for example, a square head, the shank sealably locatable and removable from the jacket and having the rugose, ridged or finned surface formed thereon and the head comprising a base for a single reaction vessel or group of perhaps four such vessels.
  • the core may be made of a highly thermal conductive metal such as copper or aluminium and the fins or the like may be the more pronounced toward the end thereof distal from the head thereby to assist in drawing heat away from the head.
  • the core may have a bore therein, perhaps axial, for electrical conduits and may further carry at the shank distal end a printed circuit board (pcb) carrying various electrical command, control and communications elements.
  • pcb printed circuit board
  • the core in the 96n microtitre vessel context has a head 2cm square and a total length not exceeding about 3cm.
  • a peitier cell may be mounted upon the core head and arranged to be initiated cyclically to assist in the removal of heat from the reaction vessel during a cooling part of a cycle and, with polarity perhaps reversed, to resist the downward flow of heat in a heating part of the cycle.
  • the peitier cell may, particularly in the 96n microtitre vessel context, comprise a group of four discrete cells or perhaps a single cell having a common base plate and one operative upper plate per vessel, ie. perhaps four operative upper plates. Typically in that context the peltier cell may measure 8mm square per reaction vessel.
  • the peltier cell may further be formed with one or more holes in the base plate thereof to enable the electrical conduits thereto to pass directly downward rather than out at edges thereto. This can be particularly useful if the peltier cell is mounted upon a pcb in turn mounted upon a core head as the conduits can be soldered directly to the pcb.
  • the depth of the peltier cell may be relatively unimportant, though the deeper it is the more readily it resists delamination due to thermal expansion and contraction. Typically however the depth may be of the order of 2 - 3 mm, with the plates having a thickness of the order of 0.3 - 0.5 mm .
  • a heater plate may be interposed between the core head and the heater cup, or form part of the heater cup, above the peltier cell when the latter is employed.
  • the heater plate may comprise a ceramic sheet.
  • a heater element in the form of an electrical conduit may take a serpentine path between a like serpentine path of adhesive holding the heater plate in situ.
  • the heater plate may be unique to one vessel or group of, for example, four vessels.
  • a temperature sensor may be disposed centrally below the heater plate. Whilst sensors are available which are very thin, eg less than 2mm, even 1 mm, a recess or hole in the heater plate may allow location of the sensor.
  • the sensor may be connected to the pcb below the core shank. In an alternative construction the sensor is mounted in the heater cup or on the heater plate just below the vessel, where there is, as mentioned above, preferably a hot spot reduction void.
  • the pcb may incorporate an H bridge for controlling the direction of current to the peltier cell and means for controlling the heat cycle, including reference to the sensor.
  • the peltier cell is mounted on a pcb there may be a void in the pcb, or between pcb's allowing the more rapid transfer of heat to the core.
  • the pcb may incorporate voids containing thermally conductive material.
  • the attachment of the various elements one to another may be effected using indium based solders, this constituting a highly thermally conductive but mechanically flexible medium.
  • the vessel receiving portion may comprise a tray, perhaps substantially flat, and perhaps rectangular, with low side walls. It may thus be adapted to receive a slide or a capsule carrying the reactants.
  • the vessel receiving portion may define a slot adapted to receive a reaction chamber formed on part of a slide, the slide being perhaps of credit card dimensions and, perhaps, structure.
  • a slide may incorporate enclosed channels wherein reactants are propelled from one station to another to undergo successive stages in a biological, chemical or bio-chemical process.
  • a particular advantage of the vessel cup assembly according to the present invention is that it, or an array thereof, can readily be incorporated into apparatus for carrying out a chemical, biological or biochemical process.
  • the apparatus comprises a platform upon which the vessel cup array may be installed, the platform then raised to a process station and lowered therefrom upon completion of the process.
  • the platform may incorporate the cooling station or part of the cooling system where the vessel cup assembly also comprises part of a cooling system, in particular an attached pettier cell or TEC.
  • Figure 1 is a schematic side elevation of first embodiment of a vessel cup assembly in accordance with the invention
  • Figure 2 is a section on ll-ll in figure 1 but showing a reaction vessel in place.
  • Figure 3 is a schematic side view of a second embodiment of a vessel cup assembly in accordance with this invention.
  • Figure 4 is a section on IV-IV in figure 3;
  • Figure 5 is a side elevation of a further vessel cup assembly embodiment
  • Figure 6 is a section on VI-VI in figure 5;
  • Figure 7 is a side view of a vessel cup assembly adapted for reception of a reaction vessel in the form of a flat faced capsule or slide;
  • Figure 8 is a section on VIII-VIII in figure 7;
  • Figure 9a is an exploded isometric view of a peltier cell
  • Figure 9b is an exploded side view of the cell of figure 9a;
  • Figure 9c is a section on JX-IX in figure 9b.
  • Figure 9d is a plan view of the cell shown in figure 9b.
  • Illustrated in figures 1 and 2 is a vessel cup assembly having, in order from top to bottom a vessel receiving portion 100, a heater portion 101 and a cooling portion 102. There is an annular anchor stop 103 between the cooling portion 102 and the heater portion 101 .
  • the vessel receiving portion 00 is in the form of a cup for receiving snugly a reaction vessel.
  • the wall of the cup wall tapers down towards the open upper end with a taper angle of about 4°.
  • the cup entry wall thickness is about 0.4 mm and the cup base wall thickness is about 0.95mm.
  • At the base of the vessel receiving portion 100 an allowance is made for a gap 100a between the base and the bottom of the reaction vessel.
  • the gap 100a will be of the order of 2 to 4 mm deep.
  • a temperature sensor receiving recess 104 At a convenient intermediate station along the length of the cup 100 is a temperature sensor receiving recess 104. In this recess is located a thermistor 105.
  • Measurement Specialties Ltd have supplied a suitable bare thermistor having a length under 3mm and a mean diameter of the order of 0.2mm. To ensure safe anchorage of this thermistor 105 into its recess 104 the thermistor tail wire is wound around the vessel receiving portion 1 00 a couple of times. The thermistor 105 is located a short distance above the heater so as not to read heater temperature but the temperature of the cup. The thermistor is arranged to operate in a predictive mode.
  • the heater portion 101 has an external spiral screw-thread-like groove 101 a of V profile for seating a heater wire coil 106 (shown in figure 5).
  • the wire is nickel chrome 0.21 mm diameter arranged to be driven with a voltage of 24 volts and capable of drawing a maximum current of 2.2 amps.
  • the length of the wire in this micro-titre vessel context is 36 cm.
  • An ultra-violet curable glue is employed in retaining the wire 1 06 in place.
  • the groove 1 01 a is formed so that when the rod is anodised adjacent wire coils do not contact one another.
  • the cooling portion 1 02 is constructed as an anchor member to anchor the assembly into a reaction vessel receiving station in a cooler assembly in or for a chemical and/or biological reaction apparatus.
  • the cooling portion 1 02 is formed in relation to the cooler assembly so as to be contiguous therewith both at periphery and at base .
  • a 1 .0mm blind hole at the base of the cooling assembly cooling portion receiving well serves to contain air compressed during fitment of one to the other.
  • the annular anchor stop 1 03 controls the depth of the cooling portion to visibly assure that the cooling portion is home.
  • Figure 2 demonstrates the fitting of a reaction vessel 200 in the cup 100.
  • the vessel is a microtitre reaction vessel comprising a reaction chamber 201 and a funnel portion 202.
  • the reaction chamber portion is a snug fit in the vessel receiving portion 100, leaving the gap 100a between them at the bottom of the reaction vessel.
  • the funnel portion 202 receives a lid of a transparent material.
  • a further probe or pip may extend from the base of the cooling portion 102 and project into coolant, the cooling assembly being arranged, of course, for such projection to occur.
  • a probe or pip may serve as a spigot whilst winding the wire coil, after which it may be removed.
  • the vessel cup assembly shown in figures 1 and 2 is formed by turning from a rod of aluminium alloy which is anodized, after machining, for electrical insulation purposes. It is accordingly of integral construction.
  • the embodiment of the invention illustrated in Figures 3 and 4 has a vessel receiving portion 300 and a heater portion 301 similar to those of the embodiment described with respect to figures 1 and 2.
  • the cooling portion 302 is of frustoconical form with the base broader than the apex so as to maximize the surface of contact with cooling apparatus, in this case a peltier cell 303, to the upper plate 304 of which it is attached.
  • At least the base of the cooling portion (the shoe 305) is formed from copper the more readily to attach it with solder.
  • the copper shoe 305 is swaged to the cooling portion 302.
  • the vessel cup assembly illustrated in figures 3 and 4 is otherwise formed from machinable aluminium rod.
  • the cooling block 307 is constructed to fit tightly into a heat reduction module which, in this instance, will stabilise the temperature of the lower plate 306.
  • the vessel cup assembly illustrated in figures 5 and 6 is similar to that illustrated in figures 3 and 4 except that the cooling block 307 has formed thereon a probe 308.
  • the probe 308 is formed with fins 309 thereon adapted for projection into a coolant liquid duct in a heat reduction module (HRM).
  • HRM heat reduction module
  • Indium based solder is used for the attachment of the shoe 305 to the peltier cell upper plate 304 and of the lower plate 306 to the secondary cooling block 307.
  • the vessel cup assembly illustrated in figures 7 and 8 is similar to those illustrated in figures 3 and 4 except that the vessel receiving portion 700 is frustoconical in form.
  • the portion 700 has a shallow tray 701 formed therein and adapted to receive a reaction vessel in the form of a flat capsule or slide.
  • the peltier cell (TEC) shown in figures 9a - 9d can be the cell 303 shown in figures 3 to 6. It comprises the basic peltier cell 900 with a ceramic heater plate 901 and a serpentine heater element 902 sandwiched between the plate 901 and the cell 900 itself.
  • the vessel cup assembly illustrated in figures 1 to 4 has an overall length of 26 mm, a cup external diameter (vessel receiving portion 100, 300) of 5.0 mm and a cooling portion 102 of 6.0 mm diameter. If a pip remains with the cooling portion 102 its dimensions are typically 4.0 mm long and 3.0 mm diameter.
  • HRM heat reduction module
  • the receiving stations are in square array on 1 .0 cm centres.
  • the heat reduction module is a machinable aluminium block incorporating a labyrinth of channels for coolant liquid. It is formed as separate blocks mating at half channel depth.
  • the heat reduction module is mounted in a reaction apparatus which houses also a reservoir of coolant liquid and means for controlling the temperature thereof. Entry and exit manifolds of the heat reduction module are connected to this reservoir.
  • the HRM forms part of a platform arranged in reaction apparatus to be available for the reception of an array of reaction vessels containing reactants and to which their lids have been fitted, the platform also having an associated sprung lift device.
  • the apparatus is thus constructed to raise the platform and press the reaction vessels via the lids thereof against a pressure plate to maintain the reaction vessels in even snug contact with the vessel cup assemblies during the reaction process.
  • the pressure plate is perforated adjacent the centre of the lids to assist visibility of the reactants to apparatus optical equipment.
  • the HRM is mounted on an elevator toward the top of which is a heater plate, foraminous coincidental with the reaction vessel lids.
  • the compression plate ensures that the reaction vessels are in snug contact with the cup receiving portions of their corresponding vessel cup assembly.
  • Optical interrogation apparatus is sited above the compression plate. The reaction can then commence.
  • the reactants in the vessels are brought to the upper temperature for denaturing the DNA in the reactants, held briefly at that temperature, cooled to the intermediate, annealing temperature and held briefly there, then cooled to the lower temperature where denatured DNA extends and held briefly there, this cycle being repeated several times until a change of colour is detected in the reactants.

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  • Chemical & Material Sciences (AREA)
  • Health & Medical Sciences (AREA)
  • Clinical Laboratory Science (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Engineering & Computer Science (AREA)
  • Biochemistry (AREA)
  • Molecular Biology (AREA)
  • General Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Mechanical Engineering (AREA)
  • Physics & Mathematics (AREA)
  • Thermal Sciences (AREA)
  • General Engineering & Computer Science (AREA)
  • Apparatus Associated With Microorganisms And Enzymes (AREA)
  • Measuring Or Testing Involving Enzymes Or Micro-Organisms (AREA)

Abstract

L'invention concerne un ensemble de cupule à cuve destiné à recevoir une cuve à réaction chimique et/ou biologique contenant des réactifs et á y traiter la réaction, et comprenant : une partie de réception de cuve à réaction ; une partie d'élément chauffant ; et une partie de refroidissement ; l'ensemble étant construit d'un seul tenant.
PCT/GB2011/001565 2010-11-08 2011-11-08 Chauffage et refroidissement de cuves à réaction biologique à faible volume WO2012063011A2 (fr)

Priority Applications (5)

Application Number Priority Date Filing Date Title
GB1308226.8A GB2501011A (en) 2010-11-08 2011-11-08 Heating and cooling low volume biological reaction vessels
US13/261,654 US20150144299A1 (en) 2010-11-08 2011-11-08 Apparatus including a vessel cup assembly for heating and cooling low volume biological reaction vessels and methods associated therewith
EP11796763.8A EP2637789A2 (fr) 2010-11-08 2011-11-08 Chauffage et refroidissement de cuves à réaction biologique à faible volume
JP2013537198A JP5892709B2 (ja) 2010-11-08 2011-11-08 低容量生物学的反応容器の加熱及び冷却
CN201180060968.8A CN103260760B (zh) 2010-11-08 2011-11-08 加热和冷却小体积生物反应容器

Applications Claiming Priority (4)

Application Number Priority Date Filing Date Title
GB1018794.6 2010-11-08
GBGB1018794.6A GB201018794D0 (en) 2010-11-08 2010-11-08 Heating and cooling low volume biological reaction vessels
GB1100625.1 2011-01-14
GBGB1100625.1A GB201100625D0 (en) 2011-01-14 2011-01-14 Reaction vessel receiving station

Publications (2)

Publication Number Publication Date
WO2012063011A2 true WO2012063011A2 (fr) 2012-05-18
WO2012063011A3 WO2012063011A3 (fr) 2012-08-02

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US (1) US20150144299A1 (fr)
EP (1) EP2637789A2 (fr)
JP (1) JP5892709B2 (fr)
CN (1) CN103260760B (fr)
GB (1) GB2501011A (fr)
WO (1) WO2012063011A2 (fr)

Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2015114296A1 (fr) * 2014-01-29 2015-08-06 Bg Research Ltd Appareil et procédé permettant d'effectuer des réactions biochimiques par thermocycleur
EP3476482A1 (fr) * 2017-10-25 2019-05-01 Stratec SE Appareil de cycle thermique
EP3887050A4 (fr) * 2018-11-26 2022-10-12 Terrabio spolka z ograniczona odpowiedzialnoscia Dispositif pour conduire des réactions d'amplification biologique

Families Citing this family (10)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN106269014A (zh) * 2016-08-22 2017-01-04 杭州迈的智能科技有限公司 能够实现固化溶液自动转换的试管箱机构及其控制方法
KR20190059289A (ko) * 2016-09-09 2019-05-30 에어월, 엘엘씨 개인용 주변 공기 온도 조절 장치
IT201600121240A1 (it) * 2016-11-30 2018-05-30 O M Z Officina Mecc Zanotti S P A Procedimento per la realizzazione di contenitori per prodotti cosmetici
FR3076395B1 (fr) * 2017-12-28 2020-01-17 Thales Dispositif de controle thermique d'un composant, systeme electronique et plate-forme associes
CN109556929A (zh) * 2018-10-18 2019-04-02 广州安必平医药科技股份有限公司 反应仓、抗原修复仪及其使用方法
DE102018132120B4 (de) * 2018-12-13 2024-04-18 Fraunhofer-Gesellschaft zur Förderung der angewandten Forschung e.V. Probenaufnahmeeinrichtung für biologische Proben mit einer Probenaufnahme aus Kohlenstoff-basiertem Werkstoff
CN110631886A (zh) * 2019-06-26 2019-12-31 金寓润泽(北京)科技有限责任公司 一种质控分析物的储存管
KR20210018761A (ko) * 2019-08-09 2021-02-18 에이에스엠 아이피 홀딩 비.브이. 냉각 장치를 포함한 히터 어셈블리 및 이를 사용하는 방법
CN111403584B (zh) * 2019-12-23 2023-03-10 杭州大和热磁电子有限公司 一种适用于非气密封装的热电模块及其制造方法
CN114669341A (zh) * 2020-12-24 2022-06-28 厦门致善生物科技股份有限公司 反应装置及医疗设备

Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4683195A (en) 1986-01-30 1987-07-28 Cetus Corporation Process for amplifying, detecting, and/or-cloning nucleic acid sequences
US4683202A (en) 1985-03-28 1987-07-28 Cetus Corporation Process for amplifying nucleic acid sequences
US5455175A (en) 1990-06-04 1995-10-03 University Of Utah Research Foundation Rapid thermal cycling device
US6171785B1 (en) 1991-05-02 2001-01-09 Roche Molecular Systems, Inc. Methods and devices for hemogeneous nucleic acid amplification and detector

Family Cites Families (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
ATE62578T1 (de) * 1984-11-09 1991-05-15 Cryologic Pty Ltd Kryogensystem fuer biologisches material.
CN1047330C (zh) * 1993-12-30 1999-12-15 加藤圭一 加热与冷却设备
DE4435107C1 (de) * 1994-09-30 1996-04-04 Biometra Biomedizinische Analy Miniaturisierter Fluß-Thermocycler
US6558947B1 (en) * 1997-09-26 2003-05-06 Applied Chemical & Engineering Systems, Inc. Thermal cycler
US8676383B2 (en) * 2002-12-23 2014-03-18 Applied Biosystems, Llc Device for carrying out chemical or biological reactions
GB0718250D0 (en) * 2007-08-29 2007-10-31 B G Res Ltd Improvements in and relating to reaction apparatus
CN200970527Y (zh) * 2006-11-13 2007-11-07 方针 生化智能温度控制实验仪
GB0813562D0 (en) * 2008-07-24 2008-09-03 Bg Res Ltd Improvements in reactor apparatus

Patent Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4683202A (en) 1985-03-28 1987-07-28 Cetus Corporation Process for amplifying nucleic acid sequences
US4683202B1 (fr) 1985-03-28 1990-11-27 Cetus Corp
US4683195A (en) 1986-01-30 1987-07-28 Cetus Corporation Process for amplifying, detecting, and/or-cloning nucleic acid sequences
US4683195B1 (fr) 1986-01-30 1990-11-27 Cetus Corp
US5455175A (en) 1990-06-04 1995-10-03 University Of Utah Research Foundation Rapid thermal cycling device
US6171785B1 (en) 1991-05-02 2001-01-09 Roche Molecular Systems, Inc. Methods and devices for hemogeneous nucleic acid amplification and detector

Cited By (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2015114296A1 (fr) * 2014-01-29 2015-08-06 Bg Research Ltd Appareil et procédé permettant d'effectuer des réactions biochimiques par thermocycleur
WO2015114295A1 (fr) * 2014-01-29 2015-08-06 Bg Research Ltd Appareil et procédé d'opérations biochimiques thermocycliques
WO2015114297A1 (fr) 2014-01-29 2015-08-06 Bg Research Ltd Procédé et appareil pour réactions
WO2015114294A1 (fr) * 2014-01-29 2015-08-06 Bg Research Ltd Identification d'agents pathogènes sur le terrain
EP3476482A1 (fr) * 2017-10-25 2019-05-01 Stratec SE Appareil de cycle thermique
EP3887050A4 (fr) * 2018-11-26 2022-10-12 Terrabio spolka z ograniczona odpowiedzialnoscia Dispositif pour conduire des réactions d'amplification biologique
US12083522B2 (en) 2018-11-26 2024-09-10 Terrabio Spolka Z Ograniczona Odpowiedzialnoscia Device for conducting biological amplification reactions

Also Published As

Publication number Publication date
GB201308226D0 (en) 2013-06-12
WO2012063011A3 (fr) 2012-08-02
CN103260760B (zh) 2016-10-19
EP2637789A2 (fr) 2013-09-18
GB2501011A (en) 2013-10-09
JP2013544088A (ja) 2013-12-12
US20150144299A1 (en) 2015-05-28
CN103260760A (zh) 2013-08-21
JP5892709B2 (ja) 2016-03-23

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