WO2005058501A1 - Chauffage d'echantillons dans un porte-echantillons - Google Patents

Chauffage d'echantillons dans un porte-echantillons Download PDF

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Publication number
WO2005058501A1
WO2005058501A1 PCT/GB2004/005298 GB2004005298W WO2005058501A1 WO 2005058501 A1 WO2005058501 A1 WO 2005058501A1 GB 2004005298 W GB2004005298 W GB 2004005298W WO 2005058501 A1 WO2005058501 A1 WO 2005058501A1
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WO
WIPO (PCT)
Prior art keywords
temperature
carrier
sensors
current
trpower
Prior art date
Application number
PCT/GB2004/005298
Other languages
English (en)
Inventor
Ian Alan Gunter
Original Assignee
Bjs Company 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 AU2002324154A external-priority patent/AU2002324154B2/en
Priority claimed from GB0329356A external-priority patent/GB0329356D0/en
Application filed by Bjs Company Ltd filed Critical Bjs Company Ltd
Publication of WO2005058501A1 publication Critical patent/WO2005058501A1/fr

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Classifications

    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • 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
    • B01L7/00—Heating or cooling apparatus; Heat insulating devices
    • B01L7/54—Heating or cooling apparatus; Heat insulating devices using spatial temperature gradients
    • G—PHYSICS
    • G05—CONTROLLING; REGULATING
    • G05D—SYSTEMS FOR CONTROLLING OR REGULATING NON-ELECTRIC VARIABLES
    • G05D23/00—Control of temperature
    • G05D23/19—Control of temperature characterised by the use of electric means
    • G05D23/1927—Control of temperature characterised by the use of electric means using a plurality of sensors
    • G05D23/193—Control of temperature characterised by the use of electric means using a plurality of sensors sensing the temperaure in different places in thermal relationship with one or more spaces
    • G05D23/1932—Control of temperature characterised by the use of electric means using a plurality of sensors sensing the temperaure in different places in thermal relationship with one or more spaces to control the temperature of a plurality of spaces
    • 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
    • B01L2200/143—Quality control, feedback systems
    • B01L2200/147—Employing temperature sensors
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2300/00—Additional constructional details
    • B01L2300/08—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
    • B01L2300/18—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

Definitions

  • This invention relates to methods and apparatus for heating samples carried in wells in a specimen carrier.
  • the methods and apparatus may be used for thermally cycling an array of small contained specimens such as may be used in a thermal cycler for performing polymerase chain reaction (PCR) processes.
  • PCR polymerase chain reaction
  • apparatus for heating samples comprising: a specimen carrier in the form of a metallic sheet, in which sheet a matrix of sample wells is incorporated; and a temperature control arrangement for controlling the temperature of the carrier, the temperature control arrangement comprising a plurality of electrical current sources for applying electrical heating current through the carrier, each current source connected across the carrier and the current sources together providing a variety of different possible current flow paths whereby localised regions of the carrier may be selectively heated, a control unit for controlling the current sources, and an array of temperature sensors for sensing the temperature of the carrier at a plurality of spaced locations, wherein the temperature control arrangement is arranged to control the temperature of the carrier in dependence on the outputs of the array of sensors in such a way as to cause the temperature of the plurality of spaced locations of the carrier to tend towards a target temperature distribution and is further arranged so that a distribution specific offset is applied to the output of at least one of the temperature sensors in the process of controlling the temperature of the carrier to cause the temperature of the plurality of
  • the expression distribution specific offset is used to refer to an offset which is applied in the present apparatus or method in order to cause the temperature of the carrier to head towards the desired temperature distribution. As such it is distinct from any general offset that may be applied to the output of a temperature sensor for the purpose of calibration etc.
  • the target temperature distribution may correspond to a generally uniform temperature gradient across a working area of the carrier.
  • the target temperature distribution may correspond to a non-uniform temperature as seen by the sensors which is chosen with the aim of obtaining a uniform temperature in each of the wells of the carrier.
  • the target temperature distribution may include one or more generally uniform temperature gradient.
  • the target temperature distribution may be one where the target temperature as seen by the sensors around the periphery of the carrier is higher than the target temperature as seen by the sensors away from the periphery of the carrier.
  • a distribution specific offset is applied to the outputs of a plurality of the temperature sensors.
  • the distribution specific offset may be applied to a subset of the plurality of the temperature sensors.
  • a second distribution specific offset may be applied to the output of at least one respective other sensor.
  • the second distribution specific offset may be applied to a second subset of the plurality of temperature sensors.
  • the second distribution specific offset may be of different magnitude and/or opposite sign to the first distribution specific offset.
  • a plurality of distribution specific offsets may be used and each applied to a respective subset of the plurality of temperature sensors.
  • the temperature control arrangement may be arranged for calculating a mean value based on the outputs of a plurality of the temperature sensors.
  • the mean value may be a weighted mean.
  • the or each distribution specific offset may be applied to a respective mean value calculated from the outputs of the respective temperature sensors.
  • the or each distribution specific offset may be applied to the outputs of the sensors before the mean value is calculated.
  • the sensors may be provided in rows on the carrier and the distribution specific offset may be applied to the outputs of a plurality of sensors in one of the rows.
  • the offset may be applied to a mean value calculated from the outputs of the sensors in said one of the rows.
  • the second distribution specific offset may be applied to the outputs of a plurality of sensors in another of the rows. Further respective distribution specific offsets may be applied to the outputs of sensors in further rows.
  • At least one control offset may be applied to the output of at least one of the temperature sensors.
  • the control offset may be used for purposes other than influencing the temperature distribution achieved.
  • the control offset may be used to control which heating pattern is selected.
  • the control offset may be a zone offset.
  • the temperature control arrangement may further comprise at least one fan for cooling the carrier.
  • the temperature control arrangement may be arranged for using the at least one fan for selectively cooling a respective localised region of the carrier.
  • the temperature control arrangement may comprise a plurality of fans for cooling the carrier, each fan may be arranged for cooling at least one respective localised region of the carrier.
  • Ducting may be provided for directing air flow at said localised regions of the carrier. In some circumstances cooling the central region of the carrier can be problematic. Ducting may be provided for directing air at the central region of the carrier. The central region at which air is directed can be small.
  • a tube which may have a diameter of in the order of 2.5 mm may be provided for directing airflow to the central region.
  • cooling and/or heating may be used.
  • the temperature control arrangement may be arranged for
  • the control unit may be arranged to control the at least one fan.
  • the control unit may have inputs that are connected to the temperature sensors.
  • the control unit may be arranged under the control of software.
  • the software comprises a portion which is arranged to receive temperature values which are dependent on the outputs of the sensors, and
  • the temperature control arrangement is arranged so that at least one of said received values includes said distribution specific offset.
  • This set of embodiments has the advantage that an algorithm which is written with the primary aim of obtaining uniform temperature in a working area of the carrier may also be used in an apparatus which is intended to provide a different temperature distribution. It is particularly useful for obtaining gradient distributions.
  • the distribution specific offset may be applied in software to values input into the control unit from the sensors. Again the offset may be applied to a mean value calculated from the outputs of a subset of the sensors.
  • the temperature control arrangement may be arranged for selectively controlling the temperature of the carrier in such a way as to cause the temperature of the plurality of spaced locations of the carrier to tend towards a respective selected one of a plurality of target temperature distributions.
  • At least one of the target temperature distributions may require no distribution specific offset to be applied to the output of any sensor.
  • one of the plurality of target temperature distributions corresponds to the temperature of a working area of the carrier being generally uniform.
  • the temperature control arrangement may be arranged for dynamically varying the or each control offset and/or distribution specific offset during operation.
  • the offsets used in heating may be different to the offsets used in cooling.
  • the apparatus may be arranged for thermally cycling samples and may be further arranged for dynamically varying the or each offset during cycling.
  • the temperature control arrangement may comprise a plurality of bus bars for
  • the carrier may comprise an interface region which surrounds a working region of the carrier.
  • the bus bars may be connected to the interface region.
  • the interface region may be continuous.
  • the working region of the carrier may be substantially square and two bus bar portions may be connected towards each corner of the square
  • Each current source may have an associated pair of bus bar portions by which it is connected to the carrier. There may be four current sources. Each current sources may be connected between a respective adjacent
  • a method for heating samples comprising: providing a specimen carrier in the form of a metallic sheet, in which sheet a matrix of sample wells is incorporated; loading samples into a plurality of the wells; applying current to the specimen carrier, which current is applied by a plurality of sources of current, each source connected across the carrier and together providing a variety of different possible current flow paths whereby localised regions of the carrier may be selectively heated; monitoring the temperature of the carrier at a plurality of spaced locations using an array of temperature sensors; controlling the temperature of the carrier in dependence on the outputs of the array of sensors in such a way as to cause the temperature of the plurality of spaced locations of the carrier to tend towards a target temperature distribution; and applying a distribution specific offset to the output of at least one of the temperature sensors in the process of controlling the temperature of the carrier to cause the temperature of the plurality of spaced locations of the carrier to tend towards the target temperature distribution.
  • the method of heating samples may comprise the step of thermally cycling the samples.
  • different distribution specific offsets may be used at different points in the cycle. This can allow the effects of different heating patterns to be studied and/or help to achieve desired heating patterns.
  • a computer program for use with apparatus for heating samples comprising: a specimen carrier in the form of a metallic sheet, in which sheet a matrix of sample wells is incorporated; and a temperature control arrangement for controlling the temperature of the carrier, the temperature control arrangement comprising a plurality of electrical current sources for applying electrical heating current through the carrier, each current source connected across the carrier and the current sources together providing a variety of different possible current flow paths whereby localised regions of the carrier may be selectively heated, a control unit for controlling the current sources, and an array of temperature sensors for sensing the temperature of the carrier at a plurality of spaced locations, and the program comprising code portions for arranging the temperature control arrangement to control the temperature of the carrier in dependence on the outputs of the array of sensors in such a way as to cause the temperature of the plurality of spaced locations of the carrier to tend towards a target temperature distribution and so that a distribution specific offset is applied to the output of at least one of the temperature sensors in the process of controlling the temperature of the carrier to
  • the computer program may be carried on at least one computer readable data carrier such as a signal, a floppy disk, a hard disk, a CD-ROM , a DND-ROM and so on.
  • apparatus for heating samples comprising: a specimen carrier in the form of a metallic sheet, in which sheet a matrix of sample wells is incorporated; and a temperature control arrangement for controlling the temperature of the carrier, the temperature control arrangement comprising a plurality of electrical current sources for applying electrical heating current through the carrier, each current source connected across the carrier and the current sources together providing a variety of different possible current flow paths whereby localised regions of the carrier may be selectively heated, and a control unit for controlling the current sources, wherein a working region of the specimen carrier is generally square and the working region of the carrier is surrounded by a continuous interface region via which the current sources are connected to the carrier.
  • each current source may be connected between a respective adjacent pair of corners of the generally square working region, such that one current source is connected between each adjacent pair of corners.
  • apparatus for heating samples comprising: a specimen carrier in the form of a metallic sheet, in which sheet a matrix of sample wells is incorporated; and a temperature control arrangement for controlling the temperature of
  • the temperature control arrangement comprising a plurality of electrical current sources for applying electrical heating current through the carrier, each current source connected across the carrier and the current sources together providing a variety of different possible current flow paths whereby localised regions of the carrier may be selectively heated, a control unit for controlling the current sources, and an array of temperature sensors for sensing the temperature of the carrier at a plurality of spaced locations, wherein the temperature control arrangement is arranged to control the temperature of the carrier in dependence on the outputs of the array of sensors in such a way as to cause the temperature of the plurality of spaced locations of the carrier to tend towards a target temperature distribution which corresponds to a generally uniform temperature gradient across a working area of the carrier.
  • apparatus for heating samples comprising: a specimen carrier in the form of a metallic sheet, in which sheet a matrix of sample wells is incorporated; and a temperature control arrangement for controlling the temperature of the carrier, the temperature control arrangement comprising a plurality of electrical current sources for applying electrical heating current through the carrier, each current source connected across the carrier and the current sources together providing a variety of different possible current flow paths whereby localised regions of the carrier may be selectively heated, a control unit for controlling the current sources, and an array of temperature sensors for sensing the temperature of the carrier at a plurality of spaced locations, wherein the temperature control arrangement is arranged to selectively control the temperature of the carrier in dependence on the outputs of the array of sensors in such a way as to cause the temperature of the plurality of spaced locations of the carrier to tend towards a first temperature distribution corresponding to a working area of the carrier having a generally uniform temperature and in such a way as to cause the temperature of the plurality of spaced locations of the carrier to tend
  • Figure 1 schematically shows the physical arrangement of part of an apparatus for heating samples
  • Figure 2 schematically shows the functional arrangement of the components forming the part of the apparatus for heating samples shown in Figure 1;
  • FIG. 3 is a block diagram schematically showing the electronic control system of the apparatus for heating samples shown in Figures 1 and 2;
  • FIG 4 schematically shows part of the cooling system of the apparatus for heating samples shown in Figures 1 to 3;
  • FIGs 5 to 12 schematically show current flow patterns through the specimen carrier of the apparatus shown in Figures 1 to 4 when being subjected to different modes of zonal heating;
  • Figure 13 is a flow chart showing, in outline, the operation of a computer program used to control the apparatus for heating samples shown in Figures 1
  • the present apparatus and method may be used for heating samples disposed in a specimen carrier 1 (see Figure 1) which forms part of the apparatus for heating samples.
  • the apparatus and method may be used in PCR processes.
  • the apparatus comprises means for heating the specimen carrier, means for cooling the specimen carrier and means for controlling these heating and cooling operations in order to achieve a desired temperature distribution in a working area la of the specimen carrier.
  • temperature control is achieved by using software to control the heating and cooling means.
  • the desired outcome is achieving thermal uniformity within the working area la of the specimen carrier and the software is arranged to do this by monitoring the temperature of the carrier 1 at a plurality of different points and controlling the heating and cooling means so as to heat and/or cool localised regions of the specimen carrier.
  • the specimen carrier as a whole will typically be being subjected to thermal cycling to subject the carried samples to a desired pattern of heating.
  • the program cycle As such, at any moment in time there will be a target programmed temperature for the specimen carrier dictated by the program cycle.
  • a core of the software is operating so as to tend to cause the temperature seen by each of the sensors to be the same as that seen by each of the other sensors and moreover, to be at the programmed temperature dictated by the cycle. In general terms, this is achieved by the software controlling the heating and cooling means in response to the sensed temperatures.
  • the apparatus operates such as to generate a generally uniform temperature gradient from one side of the working area la of the specimen carrier to the other. This temperature difference is maintained whilst the mean temperature of the block is following a program cycle over a range of temperatures.
  • the transition between gradient temperature mode and uniform temperature mode is made entirely in software.
  • the core of the software mentioned above can remain substantially the same for both modes by virtue of the use of distribution specific offsets which are applied to the outputs of the temperature sensors.
  • Figures 1 to 4 together show an apparatus for heating samples. It should be noted that various parts of the apparatus are omitted from some of the figures to aid clarity.
  • the apparatus comprises a specimen carrier (or block) 1 which comprises a generally square working area la including a plurality of sample wells lb.
  • the block 1 also comprises an interface region 2 which surrounds the working area la and is continuous.
  • the block 1 is connected via its interface region 2 to a plurality of bus bars 3.
  • Each of the bus bars 3 has two ends and passes through a respective toroidal transformer core 4 which carries a respective dual primary winding.
  • Each bus bar 3 acts as a single turn secondary winding of the respective transformer core 4 through which it passes.
  • the core, primary winding and bus bar 3 together make up a transformer.
  • each bus bar 3 is connected to the interface region 2 at a respective corner such that the pair of ends of each bus bar 3 are connected to a respective pair of adjacent corners of the interface region 2.
  • each corner of the interface region 2 has connected to it, two bus bars and each bus bar 3 is in effect connected across one edge of the working area la of the block 1.
  • the block 1 comprises a sheet of silver which is 0.35 mm thick.
  • the square working area la is 75 mm x 75 mm and the wells lb are arranged in an 8 x 8 anay having a 9 mm pitch.
  • Each of the wells is conical with a 5.5 mm diameter at the surface of the block 1 and has a depth of 11 mm.
  • a perforated silver baseplate (not shown) which is 0.5 mm thick is soldered to the tips of each of the conical wells and to the interface region 2. This results in a very rigid three dimensional structure.
  • the interface region 2 is shaped so as to project further from the working area la in the regions where it meets the bus bars 3.
  • the interface region 2 thus projects least from the working area 1 at locations towards the mid-point of each side of the working area and there is a smooth arcuate sweep in the edge of the interface region 2 between these mid-points and the vertices where the bus bars 3 are connected.
  • Each of the bus bars 3 is of high conductivity copper and has a cross-sectional area of 154mm 2 .
  • the bus bars 3 are soldered to the interface region 2 at the appropriate locations.
  • thermocouples 5 are located on the underside of the block 1 to sense the temperature of the block 1 in a plurality of spaced locations. It will be noted that the thermocouples 5 are arranged in three rows of three forming a grid which is in register with the edges of the working area la. As alluded to above each of the toroidal cores 4 form part of a transformer which is used for applying heating cmxent to the block 1 via the bus bars 3. Each of these transformers is individually controllable to alter the amount of current which is fed into the block 1. In Figure 2, the electrical arrangement of these transformers 4 with regard to the block 1 and interface region 2 is more clearly shown and each of the transformers 4 is given a separate designation
  • TR1, TR2, TR3, TR4 to aid in understanding of the controllable heating patterns which may be produced and which are described in more detail further below.
  • FIG 4 shows two fans 8 and their associated ducting or nozzles 21 which are provided to assist in controlled cooling of the block 1.
  • the apparatus comprises four such fans 8 but two of these are omitted from Figure 4 for the sake of clarity.
  • a single fan could be used for cooling the block, it is preferred to use a plurality of fans since in general terms such a plurality of small fans can respond more quickly to demands for changes in rates of airflow than can a single large fan.
  • four 80 mm square radial blowers with integral d.c. motors are used.
  • the nozzle 21 of each fan 8 directs the air it generates at high velocity onto one section of the underside of the block 1.
  • each nozzle 21 is arranged so that air is directed from the respective fan to what can be termed an edge portion of the block 1.
  • the fan 8 shown at the left hand edge of the block 1 provides cooling air to the frontmost edge of the block 1
  • the fan 8 shown towards the front in Figure 4 provides cooling air to the right hand edge of the block 1.
  • the two fans not shown in the drawings provide cooling air to the other two edges.
  • the bus bars 3 are heated to an extent by the passage of the currents for heating the block 1. A much greater heating effect on the bus bars 3 is the effect of thermal conduction from the interface region 2 acting to heat the bus bars 3.
  • the bus bars 3 When the bus bars 3 are below the mean temperature of the block 1 they act as heat sinks cooling the comers of the interface region 2. This cooling of the comers will be automatically compensated for, as the heating system will automatically increase the heat input to comers of the block 1 as required.
  • the bus bars 3 are at a temperature above the mean temperature of the block 1 they act as unwanted heat sources.
  • the bus bars 3 are cooled continuously by passing air over fins (not shown) attached to the bus bars 3 adjacent to their connection to the interface region 2.
  • bus bars 3 need to be maintained at a temperature below the lowest temperature at which the block 1 is required to operate.
  • the temperature of the bus bars 3 need to be maintained below the minimum temperature in a PCR cycle which is typically of the order of 50° C.
  • PCR reagents often require thermal activation by holding them at a controlled elevated temperature for several minutes. During such long periods at a constant temperature it has been found in practice that the localised temperature of a small region at the centre of the block 1 will tend to drift up relative to the rest of the block. As described in more detail below, the block 1 will be actively controlled to maintain a constant and even temperature and heat will be applied to compensate for heat losses to ambient air and to conduction into the bus bars 3.
  • the small region at the centre of the block is unique in being completely surrounded by material at a constant temperature and equidistant from regions of significant heat loss (i.e. the sides and comers). There will therefore be no significant heat flow through this small central region under conditions of constant temperature.
  • a separate fan could be provided for supplying air to the central region to give this cooling
  • a more practical solution is to bleed off a small amount of air from a fan provided for another purpose, in this case the bus bar cooling fan.
  • a small tube of say 2.5 mm diameter may be used to direct cooling air at the centre (preferably the exact centre) of the underside of the block 1.
  • FIG 3 schematically shows the control system for controlling heating and cooling of the block 1 by making use of the currents which may be driven through the block 1 by the transformers 4 and the cooling which may be provided by the fan 8.
  • a computer 10 which operates under the control of software 9.
  • the computer 10 is connected to an analogue to digital converter 17 via a digital I/O port 12.
  • a nine channel thermocouple amplifier 18 is connected to the analogue to digital converter 17 and, in turn, the nine thermocouples 5 attached to the working area la of the block are connected to the nine channel thermocouple amplifier 18.
  • Also connected to the analogue to digital converter 17 is a thermistor amplifier 11 which amplifies values received from four thermistors 16 which are suitably placed so as to measure ambient air temperature and bus bar 3 temperature.
  • the data inputs to the computer 10 therefore comprise the temperature readings taken by the nine thermocouples 5 (after cold junction compensation in the thermocouple amplifier 18) and the temperature values sensed by the thermistors 16. Based on calculations and decisions made by the software in response to the temperature sensor inputs, the computer is able to control the transformers 4 and fans 8 as will be described in more detail below.
  • the computer 10 is connected via the digital I/O port 12 to four phase angle trigger circuits 13.
  • Each phase angle trigger circuit 13 is connected via a respective trial selection circuit 14 to a respective pair of triacs 15.
  • Each pair of triacs 15 is arranged to control the supply of mains voltage 19 to a respective transformer 4.
  • the digital I/O port 12 is also connected directly to each of the four trial selection circuits 14.
  • each of the toroidal cores forming part of the respective transformer 4 includes dual primary windings such that the four transformers may be driven in either a forward sense or a reverse sense (0 or 180° out of phase) relative to one another.
  • One of the triacs 15 associated with each transformer 4 is arranged for driving one set of primary windings and the other trial 15 associated with that transformer 4 is arranged to supply current to the other primary winding.
  • the computer 10 is able to control the sense in which each of the transformers 4 is driven by selecting the appropriate trial 15 by sending appropriate signals to the respective trial selection circuit 14.
  • the computer 10 may send control signals via the digital I/O port 12 to the respective proportional phase angle trigger circuit 13 to control whether a particular transformer 4 is operated at all.
  • the triacs 15 are arranged to proportionally control the supply of mains power 19 to the respective transformer primary windings. This in rum controls the amount of heating current which is applied via the respective bus bar 3 to the specimen carrier 1. Again the computer 10 can control the magnitude of current which the selected trial 15 supplies to the respective transformer.
  • the current supplied to the transformer primary windings will typically be in the range of 0 to 1 Amps RMS.
  • the current thereby produced in the respective bus bar 3 and connected to the block then typically ranges from 0 to 1,000 Amps RMS due to the number of turns included in the primary windings.
  • the high secondary loop currents i.e. the current in the bus bars 3 are inherently safe as only very low voltages (0.25 volts RMS) may be measured between any two points on any secondary loop.
  • the computer 10 is further connected via the digital I/O port 12 to four respective proportionally controlled power supplies 7 each of which drives a respective one of the cooling fans 8. Again under the control of software 9 the computer 10 may issue control signals via the digital I/O port 12 to control the speed of the fans 8 and hence the cooling effect which they produce.
  • each of the four transformers can be in one of three different states, i.e. off, driven in a forward sense, or driven in a reverse sense.
  • the resistive heating effect is only dependent on the shape and magnitude of the net current flow. The direction is irrelevant. Half the possible permutations may be eliminated from use on this basis. Further, some particular current flow patterns may be produced by several different permutations. Some permutations will have a transformer on, but not significantly contributing to current flow through the block. In practice, with the geometry described in the present application there are 20 different and useful current flow regimes which together with the condition where all transformers are off, gives 21 practically useable states.
  • Heating zones can be defined by the geometry of the current flow paths through and around the block 1. Definitions of the 20 individual zones used in the present embodiment are included in Table 1 below and example zones are shown in Figures 5 to 12.
  • each of the zones is given a number between 1 and 20 and for each of these numbered zones the state of each of the transformers TR1 - TR4 shown in Figures 2 and 5 to 12 is shown.
  • “for” is used to mean forward sense
  • “rev” is used to mean reverse sense
  • "off” is used to indicate that that transformer is not in use.
  • the actual sense of the transformers is not of relevance, it is the relative sense of one transformer relative to the others which is of importance. However, for the sake of convenience, in the present description, the sense in which a current flow as depicted in Figures 4 to 11 passes through a transformer in a clockwise direction around the block 1 has been described as forward and anticlockwise as reverse.
  • zone and heating patterns may be equally generated using d.c. power supplies or a.c. transformers.
  • transformers are used and therefore the +/- indication of polarity shown in Figures 5 to 12 can be interpreted as the relative phasing of a particular transformer.
  • each transformer may be driven either in phase with, or 180° out of phase with any other transformer.
  • the depiction of current flow direction and relative phasing of a particular transformer is interpreted as a snapshot taken at the peak of a single mains half cycle.
  • the shape of the current flowing is shown as shading and is an approximation to the major current flow occurring.
  • the direction of instantaneous current is shown by the arrows.
  • Table 1 also indicates those thermocouples Tl - T9 which are considered to be representative of the temperature of the respective heating zones.
  • one step is to determine a temperature which is representative of each of the 20 heating zones so that a decision can be made as to whether it is appropriate to apply heating to such a zone.
  • the heating zones do not necessarily match clearly and precisely with the position of any one or any plurality of the thermocouples 5. Therefore a temperature which is used to represent the temperature of a particular heating zone is determined by calculating a weighted mean of the readings of a selected group of thermocouples.
  • thermocouples Tl to T9 the weightings applied to each of the readings from the respective thermocouples Tl to T9 is given and as such it will be clear that where a 0% weighting is given this thermocouple is not taken into consideration at all for determining the temperature of the respective zone.
  • FIG. 5 shows the current flow path corresponding to zone 1.
  • TR1 the transformer namely TR1
  • T2 and T3 are used to calculate a temperature for zone 1 and that slightly more weighting is given to the readings from Tl and T3. It will be noticed from Figure 5 that the location of thermocouples Tl, T2 and T3 reasonably accurately corresponds to the main current flowpath associated with the zone 1.
  • Zones 2, 3 and 4 are very similar to zone 1, the only difference being that zones 2, 3 and 4 correspond to transformers TR2, TR3 and TR4 respectively being driven alone. Thus, the same sort of pattern will result and Table 1 shows the thermocouples which may be used to determined a temperature for these
  • Zones 5 and 6 are defined by the heating current flow occurring across the block 1 from comer to comer. This pattern is obtained by driving any two adjacent transformers in the same sense. There are 8 different transformer drive patterns to achieve comer to comer current flow but only two different current flow patterns.
  • Figure 6 shows the current flow pattern defining zone 5. Current is flowing from the bottom right comer to the top left comer. In the case of zone 6 current flows from the bottom left comer to the top right comer. Again the appropriate thermocouples for determining a temperature representative of these zones can be seen from Table 1.
  • Zones 7, 8, 9 and 10 are defined by a current flow pattern where current flows between one comer and its two adjacent comers. This has the useful effect of producing enhanced heating at any selected comer. This current flow pattern is produced by driving any two adjacent transformers in opposite sense.
  • Figure 7 shows the current flow pattern defining zone 7. Current is flowing from the top right comer of the block and dividing to flow to the top left and bottom right comers. Similar effects but with different orientations are obtained in zones 8, 9 and 10.
  • Zones 11 and 12 are defined by dual heating currents passing simultaneously along any two opposite edges of the block 1. This is achieved by driving any two opposite transformers in opposite sense.
  • Figure 8 shows the current flow pattern defining zone 11. Two heating currents are flowing, one across the top edge and one across the bottom edge of the block 1. Again, by referring to the Table 1 the appropriate thermocouples for use in determining a temperature for this zone can be seen as is the case for all the zones.
  • Zone 12 is similar to zone 11 but the currents flow along the other two edges of the block, i.e. the vertical edges in the orientation shown in Figure 8.
  • Zone 13 is defined by heating current flowing simultaneously along all four edges of the block 1. This provides simultaneous heating of all four edges and all four comers. This may be achieved by driving any two opposite transformers in the same sense.
  • Figure 9 shows the current flow patterns found in zone 13. In this case currents are flowing into the top right and bottom left comers of the block and out of the top left and bottom right comers.
  • Zones 14 to 20 in general terms repeat the major current flow geometries of zones 1 to 4, 5, 6 and 13 but with greatly increased magnitude of current flow.
  • zones 14 to 17 three transformers in series are used to pass current along a single edge of the block 1. This is achieved by driving any three adjacent transformers in the same sense. The edge of the block 1 connected to the transformer which is in the off state will be heated by a large current.
  • Figure 10 shows the cunent flow pattern defined in zone 14. Here transfer TR2 is in the off state and current is therefore flowing down the corresponding (right hand) edge of the block 1.
  • Zones 18 and 19 are defined by current flows from comer to comer of the block using two parallel sets of two transformers in series. This is achieved by turning all four transformers on with opposite transformers driven in opposite sense. Current will flow between the two comers at which adjacent transformers are driven in opposite sense.
  • Figure 11 shows the current flow pattern defining zone 18. Current is flowing from the top right comer to the bottom left comer of the block 1 in the orientation shown in Figure 11. Zone 19 on the other hand has current flowing from the top left comer to the bottom right comer of the block 1.
  • Zone 20 is defined by current flows passing along all four edges of the block simultaneously heating all four edges of all four comers. This is achieved by turning all transformers on with opposite transformers driven with the same sense and adjacent transformers driven in opposite sense.
  • Figure 12 shows the current flow patterns defining zone 20. Currents are flowing from the top right and bottom left comers, dividing, and flowing to the top left and bottom right comers of the block 1 in the orientation shown in Figure 12.
  • thermocouples 1 to 20 do not map on a simple one to one basis to either the well grid or to the thermocouple array.
  • the software 9 controlling the computer 10 is written in such a way that groups of thermocouples are defined, each of which groups represents the temperature of a specific heating zone. Any individual thermocouple is found in several different groups. Further, since an individual heating zone may not be contiguous the thermocouples grouped to represent the temperature of a zone may not be adjacent to each other.
  • the shape of the heating effect of a particular current flow pattern defines a zone.
  • the heating effect may not be the same at all points in the zone.
  • the temperature of the zone is determined by taking a weighted mean of the thermocouples 5 within the zone.
  • Table 1 gives the weighting applied to each of the thermocouples 5 when determining the mean temperature of each zone for control purposes.
  • the mean temperature of the block 1 is measured as the non weighted mean of all of the nine thermocouple 5 readings.
  • the apparatus includes a cooling system comprising four independently controllable fans 8 which are arranged for cooling localised areas. Again a zone control system is used with regard to cooling. There are four cooling zones corresponding to the respective areas of the block at which the nozzles 21 are directed. Again a temperature representative of the cooling zone is derived from a group of thermocouple readings.
  • a cooling zone 1 temperature is derived from thermocouples Tl, T2, T3 and T5
  • a cooling zone 2 temperature is derived from thermocouples T3, T5, T6 and T9
  • a cooling zone 3 temperature is derived from thermocouples T5, T7, T8 and T9
  • a cooling zone 4 temperature is derived from thermocouples Tl, T4, T5 and T7.
  • a mean of the four temperatures sensed by the respective group of thermocouples is used to represent the temperature of the corresponding cooling zone.
  • the operation of the cooling fans 8 is controlled making use of these temperatures which represent the four cooling zones.
  • the fans 8 are proportionally controlled as mentioned above and the magnitude of the voltage applied to each fan motor 8 is calculated based on a difference between the calculated cooling zone temperature and the desired temperature of the block 1 based on the program time/temperature profile. The calculation is refined using data on ambient air temperature, mean absolute block temperature and bus bar temperature making use of inputs from the thermocouples 5 and thermistors 16.
  • Figure 13 shows the basic control loop of the software 9 used to control the computer 10 to give the desired heating and cooling effects.
  • step 1 temperature data from the thermocouples 5 is gathered.
  • step 2 if a gradient heating pattern is to be used, temperature distribution specific offsets are applied to the outputs from the appropriate temperature sensors. If, on the other hand, uniform heating of the block 1 is required then this step may be omitted.
  • step 3 the temperature readings are sorted into zones and used to calculate representative temperatures of each of the heating and cooling zones described above.
  • step 4 the coolest heating zone is identified, that is to say that zone which has the lowest representative temperature as calculated according to the weightings shown in Table 1.
  • the appropriate heating requirement for heating that zone is determined in step 5 making reference to the program's thermal profile (i.e. the cycling regime which is to be followed) and making use of ambient air and bus bar temperature readings.
  • step 6 the appropriate transformer drive pattern is determined based on the zone which needs to be heated and in step 7 in response to this the appropriate transformers 4 are driven in the appropriate sense using the appropriate amount of power to produce the desired heating effect in the requisite zones.
  • steps 4 to 6 are being conducted for determining the appropriate heating requirement if any, the other branch of the process is used to determine if any cooling is appropriate.
  • step 8 the hottest cooling zone is identified.
  • step 9 the appropriate cooling requirement is determined making reference to the program's thermal profile and the temperature sensed by the ambient air and bus bar sensors.
  • step 10 the appropriate fan drive pattern is determined whereupon the process recombines with the heating control process such that appropriate power is applied to appropriate fans 8 in step 7.
  • step 7 where power is applied to the transformers 4 and fans 8, the step of synchronising the drive to the transformers with the mains cycle is taken.
  • thermocouple 5 signals and in the system overall are the heating currents. These are modulated symmetrically and in synchronism with the mains waveform.
  • the noise produced on the negative half cycle should cancel out the noise produced on the positive half cycle, as long as the signals are sampled and averaged over an exactly even, (as exemplified two), number of consecutive half cycles.
  • the drive to the transformer 4 provides a symmetrical waveform for at least one mains cycle. That is to say the positive and negative half cycle voltage waveforms should be perfectly mirrored about the time axis. The easiest way of ensuring this is to synchronise the drive with the mains cycle.
  • step 1 where temperature data is imported from the thermocouples 5, the software averages each of the recorded values over a period of one mains cycle to minimise the effects of mains hum pickup at the thermocouples 5.
  • 91 readings were achieved on each of the channels in each cycle, i.e. in every 0.02 seconds.
  • thermocouple 5 After the averaging of the input values has been completed, the resulting mean value for the temperature sensed by each thermocouple 5 is converted to a temperature value using stored calibration data.
  • An example portion of code for performing this function is given below and in this case it will be noted that temperature values are expressed as an integer 100 times the temperature in degrees C. This is because integer arithmetic is faster than floating point arithmetic on a PC.
  • step 2 in which gradient offsets are applied, need only be carried out if a gradient mode of heating is to be conducted and further explanation of this process will be given further below to help illustrate how the functioning of the core of the software is independent of whether a uniform mode or a gradient mode of heating is to be applied.
  • the temperature data obtained in step 1 is sorted into zones by producing weighted mean temperatures for each zone in accordance with the values given in Table 1. Further, in this step, small zone offsets are applied to some of the zone temperatures in order to bring all of the zones into use and to allow fine tuning.
  • step 3 the temperature data obtained in step 1 is sorted into zones by producing weighted mean temperatures for each zone in accordance with the values given in Table 1. Further, in this step, small zone offsets are applied to some of the zone temperatures in order to bring all of the zones into use and to allow fine tuning.
  • zone offsets are used because otherwise the best use of the heating zones cannot be achieved. For example, without some mechanism such as zone offsets, heating zones 11 or 12 could never be selected for heating.
  • thermocouples Tl ,T2, T3, T7, T8 and T9 The temperature of zone 11 is measured by thermocouples Tl ,T2, T3, T7, T8 and T9 whereas the temperature of zone 1 is measured by thermocouples Tl, T2 and T3 and the temperature of zone 3 is measured by thermocouples T7, T8 and T9. It will be remembered that the zone to be heated is selected by choosing that zone which is coolest. As a matter of practicality the mean temperature given by thermocouples Tl, T2 and T3 representative of zone 1 will always be different than the mean temperature accorded by thermocouples
  • T7 ,T8 and T9 representative of zone 3. Therefore, the temperature for zone 1 or 3 will always in practice be less than the temperature of zone 11 which in effect will have a temperature which is the average of zones 1 and 3.
  • zone 11 when heating rapidly the use of zone 11 is preferred as the total heat input is twice that which could be provided by zones 1 or 3. On the other hand, when cooling it is desirable to minimise the total heat input into the block and so use of zones 1 and 3 to control thermal uniformity is preferred to using zone 11.
  • zones 11 and 12 the mean temperatures calculated for zones 1, 2, 3 and 4 are offset by +0.1° when the temperature of the block is being raised in accordance with the program time/temperature profile. The offset is removed when the block 1 is required to maintain a constant temperature or to be cooled.
  • zones 14 to 20 are the same shape as zones 1 to 4, 5, 6 and 13 and use the same thermocouple readings but can produce greater heat input into the block.
  • Zones 14, 15, 16 and 17 are normally not preferred to zones 1, 2, 3 and 4 and so their calculated mean temperatures are offset by +0.11°. However, when the gradient function is being used a much higher heat input than normal is required to the side of the block 1 at the high side of the temperature gradient. Therefore, when the gradient function is being applied the calculated mean temperature of the appropriate high temperature side zone only (i.e. one of zones 14, 15, 16 or 17) is offset by -0.01°.
  • Zones 18, 19 and 20 are not normally preferred to zones 5, 6 and 13 so the calculated mean temperatures of these zones are normally offset by +0.01°. However, when very high heating rates are required zone 20 in particular is very effective. Therefore, when the heating rate required to follow the program time temperature profile exceeds 10° per second the calculated mean temperatures of zones 18, 19 and 20 are offset by -0.01°.
  • offsetting the temperature of a zone by a positive amount has the tendency to make this zone less likely to be selected during heating as it is less likely to be the coolest zone.
  • offsetting the temperature of a zone by a negative amount increases the likelihood of it being selected.
  • step 4 the coolest heating zone is identified and below is an example code portion which may be used for carrying out this step.
  • step 5 the magnitude of the heat input required is calculated based on the difference between the mean zone temperature and the desired temperature of the block 1 at the relevant time.
  • the calculation of required heat input is further refined using data on ambient air temperature and bus bar temperature acquired from the thermistors 16.
  • the software then controls the supply of current to the appropriate transformers 4 in step 7.
  • the transformers are proportionally controlled and the heat produced in the selected zone is proportional to the square of the current magnitude.
  • the required heat input is applied by passing an appropriate current through the path corresponding to the selected heating zone. The required input may be zero or less in which case no current is applied to the zone.
  • the software calculates the required heat input to a zone based on the difference between the calculated zone temperature and the mean temperature of the block instead of the difference between the calculated zone temperature and the program desired temperature of the block 1 as would be the case during a heating part of the cycle.
  • Step 1 and Steps 3 to 10 described above have the general purpose of trying to achieve thermal uniformity over the working area la of the block 1 during operation and in particular during thermal cycling operations. As it will be appreciated such a function is useful in its own right and can be considered to form the core of the software control system. As mentioned above however, the present apparatus also has the facility to provide gradient heating modes. In the present case gradient heating is achieved by applying distribution specific offsets to the outputs of some of the thermocouples 5 in the software, in particular in step 2.
  • the offsets are applied to the temperatures reported by the thermocouples to the core of the software.
  • the core of the software will operate to change the local temperatures around the block 1 to equalise the thermocouple readings as seen by the core of the software.
  • the control system will operate to cool the region of the block 1 sensed by thermocouples Tl, T2 and T3 and heat the region of the block sensed by thermocouples T7, T8 and T9.
  • thermocouples 5 are reporting the same temperature to the core of the software as are thermocouples T4, T5 and T6 which have not been offset.
  • This has the effect of giving a temperature difference of 2 X N degrees between one side of the block 1 and the other. The temperature along the centre of the block is maintained at the nominal (not offset) temperature.
  • thermocouples, Tl, T4 and T7 could be offset to report temperatures increased by N degrees and thermocouples T3, T6 and T9 could be offset to report temperatures decreased by N degrees.
  • the direction of the temperature gradient would then be along the opposite axis of the block.
  • Other gradient temperature distributions could be provided.
  • the magnitude of the gradient can be changed dynamically while cycling as the control of the gradient is carried out within software.
  • zero gradient can be generally applied but a gradient of N degrees may be used at the highest temperature to help find optimum melt temperatures.
  • a gradient can be applied only at lowest temperatures of the cycle in order to investigate and optimise hybridisation temperatures.
  • the gradient function can be applied only at mid range temperatures when optimising annealing temperatures. Since the gradient function is generated wholly in software, the transition from uniform to gradient temperature control and from gradient to uniform temperature control may be programmed to occur at any time and at any temperature. Generally maintaining a gradient as described will require the maintenance of heat flow along the gradient.
  • control functions are also biassed to favour higher heat generation in the region of the block which is to have the highest temperature and increased cooling in the region of the block which is to have the lowest temperature.
  • code which may be used in obtaining a temperature gradient such that the temperature of the block along the edge adjacent to thermocouples Tl - T3 is higher than the edge adjacent to thermocouples T7 to T9.
  • zone control cooling When operating in gradient temperature mode the efficiency of the apparatus is greatly enhanced by having zone control cooling. This is because cooling can be preferentially applied to the side of the block which is at the low end of the temperature gradient.
  • thermocouples are particularly advantageous and the use of offsets to the outputs of the temperature sensors, in this case thermocouples.
  • systems can be envisaged where neither of these aspects are used.
  • mechanical/electrical techniques might be used to apply offsets to the outputs of the thermocouples directly before these are
  • thermosensors 5 contact with (the underside of) the top plate of the block 1 or other positions which are not directly in the wells lb that accept the samples.
  • plastic sample carrying trays are used in the block 1 and the
  • the pattern of heat loss from the wells l b may be different from the part of the block to which the sensors 5 are attached, for example wells around the edge may lose heat much more rapidly than those at the centre, and this effect may be more extreme than in the top part of the block 1.
  • the target temperature distribution may therefore be chosen so that a higher temperature as sensed by the sensors 5 is maintained around a periphery of the block 1 compared to the centre of the block 1.
  • the target temperature distributions may be obtained using the same idea of offsets described above.
  • a program may be carried on a data carrier or plurality of data carriers such as floppy disks, hard disks,
  • CD-ROMS CD-ROMS, DVD-ROMS, etc.

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Abstract

Appareil chauffant qui utilise le chauffage résistif pour chauffer des échantillons portés dans un porte-échantillons à feuille métallique. Les effets de chauffage de gradient et d'autres modèles de chauffage sont produits par application de décalages sur les sorties des capteurs de température, qui captent la température de la feuille à différents emplacements.
PCT/GB2004/005298 2002-09-09 2004-12-16 Chauffage d'echantillons dans un porte-echantillons WO2005058501A1 (fr)

Applications Claiming Priority (4)

Application Number Priority Date Filing Date Title
US48845702A 2002-09-09 2002-09-09
AU2002324154A AU2002324154B2 (en) 2001-09-10 2002-09-09 Zone heating of specimen carriers
GB0329356.0 2003-12-18
GB0329356A GB0329356D0 (en) 2003-12-18 2003-12-18 Heating samples in specimen carriers

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Cited By (10)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2008134849A1 (fr) * 2007-05-02 2008-11-13 Spartan Bioscience Inc. Procédé d'augmentation de la vitesse de réactions d'amplification d'acide nucléique
WO2009022150A1 (fr) * 2007-08-15 2009-02-19 Enigma Diagnostics Limited Appareil et procédé pour l'étalonnage de capteurs thermiques sans contact
EP2060324A1 (fr) * 2007-11-13 2009-05-20 F.Hoffmann-La Roche Ag Unité de bloc thermique
WO2012080746A1 (fr) 2010-12-17 2012-06-21 Ian Gunter Procédés et systèmes pour chauffage de pcr rapide
WO2013175218A1 (fr) 2012-05-24 2013-11-28 Bjs Ip Limited Pince pour chauffage rapide de pcr
WO2014140596A1 (fr) 2013-03-15 2014-09-18 Bjs Ip Limited Chauffage rapide de pcr
US8945880B2 (en) 2008-07-31 2015-02-03 Spartan Bioscience, Inc. Thermal cycling by positioning relative to fixed-temperature heat source
EP2850174A4 (fr) * 2012-05-15 2015-12-30 Cepheid Appareil et méthode de cyclage thermique
US10391498B2 (en) 2015-12-11 2019-08-27 Spartan Bioscience Inc. Systems and methods for nucleic acid amplification
CN113377140A (zh) * 2021-06-09 2021-09-10 厦门大学 用于核酸检测装置的温度控制方法及装置

Citations (9)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5119884A (en) * 1989-11-30 1992-06-09 Johnson Service Company Multiple stage electronic temperature control for heating and cooling
WO1998043740A2 (fr) * 1997-03-28 1998-10-08 The Perkin-Elmer Corporation Ameliorations apportees a un cycleur thermique pour pcr
EP1157744A1 (fr) * 1990-11-29 2001-11-28 The Perkin-Elmer Corporation Réaction de polymérase en chaíne automatisée
US20020006619A1 (en) * 2000-02-23 2002-01-17 David Cohen Thermal cycler that allows two-dimension temperature gradients and hold time optimization
US6372486B1 (en) * 1998-11-30 2002-04-16 Hybaid Limited Thermo cycler
WO2003000419A2 (fr) * 2001-06-21 2003-01-03 Hybaid Limited Plaque a puits a echantillons
WO2003022439A2 (fr) * 2001-09-10 2003-03-20 Bjs Company Ltd. Chauffage de zones de porte-specimens
US6544477B1 (en) * 2000-08-01 2003-04-08 Regents Of The University Of Minnesota Apparatus for generating a temperature gradient
US20030182021A1 (en) * 2002-03-22 2003-09-25 Honeywell International Inc. Zone of greatest demand controller, apparatus, and method

Patent Citations (9)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5119884A (en) * 1989-11-30 1992-06-09 Johnson Service Company Multiple stage electronic temperature control for heating and cooling
EP1157744A1 (fr) * 1990-11-29 2001-11-28 The Perkin-Elmer Corporation Réaction de polymérase en chaíne automatisée
WO1998043740A2 (fr) * 1997-03-28 1998-10-08 The Perkin-Elmer Corporation Ameliorations apportees a un cycleur thermique pour pcr
US6372486B1 (en) * 1998-11-30 2002-04-16 Hybaid Limited Thermo cycler
US20020006619A1 (en) * 2000-02-23 2002-01-17 David Cohen Thermal cycler that allows two-dimension temperature gradients and hold time optimization
US6544477B1 (en) * 2000-08-01 2003-04-08 Regents Of The University Of Minnesota Apparatus for generating a temperature gradient
WO2003000419A2 (fr) * 2001-06-21 2003-01-03 Hybaid Limited Plaque a puits a echantillons
WO2003022439A2 (fr) * 2001-09-10 2003-03-20 Bjs Company Ltd. Chauffage de zones de porte-specimens
US20030182021A1 (en) * 2002-03-22 2003-09-25 Honeywell International Inc. Zone of greatest demand controller, apparatus, and method

Cited By (19)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2008134849A1 (fr) * 2007-05-02 2008-11-13 Spartan Bioscience Inc. Procédé d'augmentation de la vitesse de réactions d'amplification d'acide nucléique
GB2463170A (en) * 2007-05-02 2010-03-10 Spartan Bioscience Inc Method for increasing the speed of nucleic acid amplification reactions
GB2463170B (en) * 2007-05-02 2012-06-13 Spartan Bioscience Inc Method for increasing the speed of nucleic acid amplification reactions
WO2009022150A1 (fr) * 2007-08-15 2009-02-19 Enigma Diagnostics Limited Appareil et procédé pour l'étalonnage de capteurs thermiques sans contact
EP2060324A1 (fr) * 2007-11-13 2009-05-20 F.Hoffmann-La Roche Ag Unité de bloc thermique
US8739554B2 (en) 2007-11-13 2014-06-03 Roche Molecular Systems, Inc. Thermal block unit
US8945880B2 (en) 2008-07-31 2015-02-03 Spartan Bioscience, Inc. Thermal cycling by positioning relative to fixed-temperature heat source
WO2012080746A1 (fr) 2010-12-17 2012-06-21 Ian Gunter Procédés et systèmes pour chauffage de pcr rapide
US9168530B2 (en) 2010-12-17 2015-10-27 Bjs Ip Ltd. Methods and systems for fast PCR heating
US11045810B2 (en) 2012-05-15 2021-06-29 Cepheid Thermal cycling methods
US9908119B2 (en) 2012-05-15 2018-03-06 Cepheid Thermal cycling apparatus and method
EP2850174A4 (fr) * 2012-05-15 2015-12-30 Cepheid Appareil et méthode de cyclage thermique
US9579657B2 (en) 2012-05-24 2017-02-28 Bjs Ip Ltd Clamp for fast PCR heating
US10315198B2 (en) 2012-05-24 2019-06-11 Bjs Ip Ltd Clamp for fast PCR heating
WO2013175218A1 (fr) 2012-05-24 2013-11-28 Bjs Ip Limited Pince pour chauffage rapide de pcr
WO2014140596A1 (fr) 2013-03-15 2014-09-18 Bjs Ip Limited Chauffage rapide de pcr
US10391498B2 (en) 2015-12-11 2019-08-27 Spartan Bioscience Inc. Systems and methods for nucleic acid amplification
CN113377140A (zh) * 2021-06-09 2021-09-10 厦门大学 用于核酸检测装置的温度控制方法及装置
CN113377140B (zh) * 2021-06-09 2022-10-04 厦门大学 用于核酸检测装置的温度控制方法及装置

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