WO2018174818A1 - Appareil d'amplification d'acides nucléiques - Google Patents

Appareil d'amplification d'acides nucléiques Download PDF

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Publication number
WO2018174818A1
WO2018174818A1 PCT/SG2018/050121 SG2018050121W WO2018174818A1 WO 2018174818 A1 WO2018174818 A1 WO 2018174818A1 SG 2018050121 W SG2018050121 W SG 2018050121W WO 2018174818 A1 WO2018174818 A1 WO 2018174818A1
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WO
WIPO (PCT)
Prior art keywords
cap
reactor
strip
pressure
stack
Prior art date
Application number
PCT/SG2018/050121
Other languages
English (en)
Inventor
Haiqing Gong
Yan WEN
Original Assignee
Star Array Pte 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
Application filed by Star Array Pte Ltd filed Critical Star Array Pte Ltd
Publication of WO2018174818A1 publication Critical patent/WO2018174818A1/fr

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Classifications

    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N35/00—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L3/00—Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
    • B01L3/50—Containers for the purpose of retaining a material to be analysed, e.g. test tubes
    • B01L3/508—Containers for the purpose of retaining a material to be analysed, e.g. test tubes rigid containers not provided for above
    • B01L3/5085—Containers for the purpose of retaining a material to be analysed, e.g. test tubes rigid containers not provided for above for multiple samples, e.g. microtitration plates
    • B01L3/50853—Containers for the purpose of retaining a material to be analysed, e.g. test tubes rigid containers not provided for above for multiple samples, e.g. microtitration plates with covers or lids
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L3/00—Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
    • B01L3/50—Containers for the purpose of retaining a material to be analysed, e.g. test tubes
    • B01L3/508—Containers for the purpose of retaining a material to be analysed, e.g. test tubes rigid containers not provided for above
    • B01L3/5085—Containers for the purpose of retaining a material to be analysed, e.g. test tubes rigid containers not provided for above for multiple samples, e.g. microtitration plates
    • B01L3/50855—Containers for the purpose of retaining a material to be analysed, e.g. test tubes rigid containers not provided for above for multiple samples, e.g. microtitration plates using modular assemblies of strips or of individual wells
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N35/00—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor
    • G01N35/00029—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor provided with flat sample substrates, e.g. slides
    • G01N2035/00099—Characterised by type of test elements
    • G01N2035/00158—Elements containing microarrays, i.e. "biochip"
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N35/00—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor
    • G01N2035/00178—Special arrangements of analysers
    • G01N2035/00277—Special precautions to avoid contamination (e.g. enclosures, glove- boxes, sealed sample carriers, disposal of contaminated material)
    • G01N2035/00287—Special precautions to avoid contamination (e.g. enclosures, glove- boxes, sealed sample carriers, disposal of contaminated material) movable lid/cover for sample or reaction tubes

Definitions

  • the present invention relates to the field of amplification of nucleic acids for analyses.
  • PCR polymerase chain reaction
  • a large number of biological researchers use PCR and other forms of DNA amplifications in their work on nucleic acid analyses, due to its high sensitivity and specificity.
  • the PCR is conducted in a PCR thermal cycler where the nucleic acid reaction material undergoes thermal processing for DNA amplification.
  • the biological samples containing nucleic acid are processed to obtain nucleic acid in a purified or un-purified form, which are then formulated into reaction materials and loaded into reactors such as in the form of tubes or wellplates.
  • the reactors are subjected to thermal processing such as thermal cycling in a PCR module (PCRM).
  • thermal processing such as thermal cycling in a PCR module (PCRM).
  • the reaction materials tend to evaporate. This undesirably results in loss of the reaction materials. The evaporation also tends to contaminate the surroundings including the equipment areas and other reactors undergoing the same batch of the thermal processing.
  • the reactors are sealed manually with caps or by adhesive films or by films adhered under pressure, heat and the like to prevent evaporation of samples.
  • Fig la illustrates an array of reactors 5 being available as a reactor strip 4.
  • the reactor array 4 is manually sealed by the cap strip 2 to form the combined set 6 wherein each reactor 5 is sealed by a cap 3.
  • the combined set 6 then proceeds to the PCR module under a batch processing.
  • the manual sealing process is typically conducted under a controlled ambience to prevent the reaction material from getting contaminated.
  • Fig. lb shows three reactors 5 in the form of a micro- well array where a chip 5c contains multiple wells 5b which are filled with the reaction material from the inlets 5a and manually sealed at the inlets 5a.
  • the chip 5c is thereafter coated with a layer 5d as shown in the next figure, to cover the wells 5b.
  • Fig. lc shows the cross-sectional view at the cutline A- A' shown at Fig. lb.
  • Fig Id illustrates a wellplate 7 with a matrix of the reactor 5 or multiple arrays of the reactor 5 as commonly used for PCR.
  • an adhesive film 8 is fixed by pressure over the reactors 5 in the matrix as shown in Fig. le.
  • the adhesive film 8 may be fixed over the reactors 5 in the matrix by pressing with a heated roller.
  • Cepheid's GeneXpert testing process provides self-contained and single use cartridges for automatically carrying out sample preparation, amplification and detection within this self- contained instrument.
  • this instrument uses a specifically designed complex cartridge, thereby rendering a high cost for running a test and low test throughput in such an instrument.
  • the ideal automated nucleic acid testing machine should desirably be capable of handling and sealing commonly used reaction consumables like the PCR reactor 5, reactor arrays 4, and wellplate 7 which are low cost consumables.
  • the present invention provides an electro-mechanical apparatus for enabling integration of the sealing process and the PCRM at affordable cost using commonly used disposables in the industry like the PCR tubes and wellplates.
  • This invention provides a great positive impact on biological analysis by significantly reducing the time for the thermal cycling and enabling point of care (POC) applications.
  • POC point of care
  • apparatus for sealing reactors with a cap each, the reactors being loaded with reaction material for thermally processing nucleic acid comprising: a pressure means for exerting pressure on the cap or a stack of the caps such that a protruded portion in the cap or the bottom-most cap in the stack gets installed into the reactor by press-fit.
  • the press- fit mechanism applies to cases where under a pressure, a projected part in the cap strip gets engaged with the reactor for sealing.
  • the engagement may be external when the projected part goes over the external reactor surface. Alternately, the engagement may be internal when the projected part goes within the reactor.
  • the engagement may be both external and internal.
  • the apparatus handles the commercially available cheap and disposable reactors.
  • the press-fit method provides tight capping so as to prevent vaporization of the reaction material to avoid contamination of the ambience and also to avoid cross contamination from one reactor to the next.
  • the apparatus overcomes the requirement of providing a controlled ambience and trained personnel for conducting the sealing process.
  • the apparatus is robust, compact, light weight and easy to use.
  • using the cap strip and the reactor arrays or wellplates enhances the productivity by increasing the speed of sealing for the reactors in a batch.
  • this arrangement of housing and disposing the caps or cap strips one at a time is simple and efficient and needs minimal space.
  • the apparatus also allows for capping of smaller number of reactors as required than those of a wellplate, making nucleic acid testing cost-effective.
  • the cap may be a cap strip and the reactor may be a reactor array or a wellplate for more efficient batch processing.
  • the cap strip may extend to more than one row of caps when used for sealing a wellplate.
  • the apparatus further comprises a housing for accommodating the cap or the cap strip or the stack, the housing further comprising a releasing means for releasing from the housing one at a time, any one from the group consisting: a) the cap, b) the cap strip, and c) the bottom-most cap or the bottom-most cap strip. This helps to control the release of a cap or a cap strip only after the stack has been positioned over a reactor or a reactor array respectively before exerting the pressure for the installation.
  • the stack may move downwards as the bottom-most cap or the bottom-most cap strip is released from the stack for installation. This assures consistent installation of the caps over all the reactors or reactor arrays by the press-fit method and refilling the stack needs to be done only when one whole stack is released for installation.
  • the housing is internally profiled to adequately fit the lateral shape of the cap strip or the cap so that the position of the cap strip or the cap within the housing is maintained fixed. This helps the cap strip or the cap to be aligned precisely over the reactors or wellplate when released.
  • the apparatus further comprises a picking means to pick the cap (3) or the cap strip (2); and a positioning means to position the picked-up cap or the cap strip over the reactor(s) or reactor array(s) before exerting the pressure.
  • the positioning may be conducted by moving the reactors or the reactor arrays under the caps or the cap strips. Alternately the positioning may be conducted by moving the caps or the cap strips over the reactors or the reactor arrays. This is advantageous particularly when during the sealing the reactors or reactor arrays are positioned over the heating means in unheated condition in a thermal control module to save foot-print of the apparatus.
  • the housing of the caps or cap-strips can easily be moved away from the optical path between the optical detector and the reactors.
  • the cap or the cap strip is held by the picking means by vacuum suction. Holding by vacuum suction along a flat top surface of the caps or the cap strips, helps in positioning them over the reactors or the reactor arrays with greater reliability. Alternately, mechanical holders at the cost of higher complexity may be used where the top surfaces are not flat.
  • the apparatus further comprises: a sealant bath to contain a liquid sealant in use, wherein the apparatus allows the positioning means to contact a portion of the cap or the cap strip with the sealant before placing over the reactor(s) or the reactor array(s) or the wellplates.
  • the sealant helps seal any gap between the reactor and the cap during the thermal processing of the reaction material in the reactors.
  • the liquid sealant also helps with an easier installation of the cap into the reactor by lubrication, such that the pressure required for the installation is reduced and the installation is faster with higher reliability and repeatability thereby reducing the overall nucleic acid testing time. With the requirement of reduced pressure the requirements on machine rigidity and structural dimensions are also reduced.
  • the apparatus further comprises: a sealant bath in use containing a liquid sealant; and a sealant applicator for being partially dipped into the liquid sealant and then being contacted with the top inner surface of the reactor(s) to form a layer with the sealant before the sealing.
  • a sealant applicator is useful for embodiments where dipping the protruded portion of the cap in the sealant bath is not feasible.
  • the apparatus further comprises: a substantially rigid plate for being placed over the cap or the cap strip after the installation and clamped with a reactor holder holding the reactor or a heat block for heating the reactor during subsequent thermal processing.
  • a substantially rigid plate for being placed over the cap or the cap strip after the installation and clamped with a reactor holder holding the reactor or a heat block for heating the reactor during subsequent thermal processing.
  • the apparatus comprises: a rotating means; the pressure means comprises a first cam means; and the releasing means (20) comprises a second cam means, such that in operation the first and the second cam means are rotated synchronously by the rotating means.
  • deploying the single rotating means for the two cam means reduces the space and weight of the apparatus.
  • the synchronous rotation easily controls the coordination between the releasing means and the pressure means.
  • the pressure means comprises a bottom surface that in use makes contact with the top free surface of the cap or the cap strip or the stack to exert the pressure and the bottom surface is planar, the top free surface being remote from the reactor or the array of the reactors respectively during the installation.
  • the planar surface provides uniform contact of the bottom surface with the top of the stack and the pressure exerted by the pressure means is uniformly transferred over the stack.
  • the pressure means exerts downward pressure on the bottom surface while the position of the bottom surface relative to the top free surface of the stack changes from angular to parallel, while the stack moves downwards as the bottom-most cap or cap strip is released for installation.
  • this feature helps in making an initial engagement of the edge cap with the edge reactor by placing the cap strip at an angle to the reactors before capping the reactors from one side of the array to another. This makes the process of press-fitting the caps even more effective and requires generation of lesser force to press the caps into the reactors, thereby making the apparatus less bulky.
  • the pressure means comprises a pivotal means for changing the position. Changing the direction by the pivotal means advantageously allows the apparatus to be compact and less complex than with other means.
  • a bottom surface of the pressure means that makes contact with the top free surface of the stack is convex, the top free surface being remote from the reactor (5) or the array of the reactors (5) respectively during the installation.
  • the pressure exerted by the bottom surface is by swinging the convex bottom surface along the top free surface of the cap or the cap strip or the stack.
  • the pressure means comprises a pivotal means for providing the swinging.
  • the pivotal means used for swinging makes the apparatus compact and less complex than with other means.
  • the apparatus further comprises a holding means for holding a plurality of housings for accommodating multiple stacks. This feature is advantageous as the process of sealing can continue without interruption even when an empty housing is to be re-filled with the stack.
  • the pressure means comprises a saw toothed pusher; and a bottom surface, the pusher being for indexing the bottom surface downwards to assist the releasing for the installation.
  • the pressure means comprises a bottom surface; a threaded pusher; a first actuator for rotating the threaded pusher to provide a linear motion for moving the bottom surface downwards; and a sensing means to monitor and regulate movement of the cap or the cap strip.
  • the sensing means comprises at least one element from the group consisting: a) a pressure transducer for sensing the pressure exerting onto the cap or the cap strip and then regulating movement of the first actuator by a controller included in the pressure means, b) a pressure transducer for sensing the pressure exerting onto the bottom of the reactor or the reactor array and then regulating movement of the first actuator by a controller included in the pressure means, c) a contact sensor for sensing position of the cap or the cap strip and then regulating movement of the first actuator by a controller included in the pressure means, d) a proximity sensor for sensing position of the cap or the cap strip and then regulating movement of the first actuator by a controller included in the pressure means, and e) an optical sensor for sensing position of the cap or the cap strip and then regulating movement of the first actuator by a controller included in the pressure means.
  • the apparatus may further comprise a second actuator; and an unlocking means as included in the releasing means, the second actuator also being regulated by the pressure transducer or any of the sensors and the controller for operating the unlocking means while coordinating between the releasing and the installation.
  • the apparatus further comprising a securing means for securing the position of the stack above the bottom-most cap or cap strip; a transfer means for transferring the bottom-most cap or cap strip over the reactor or reactor array before the installation by the pressure means.
  • the apparatus further comprises: a first cam means for providing a reciprocating motion to a first pusher element for the installation, the first pusher element being included in the pressure means; a second cam means for providing a reciprocating motion to a movement means as included in the transfer means; and a rotating means for operating the first and the second cam means.
  • the common rotating means is useful for timely coordination between the pressure means and the transfer means.
  • the transfer means comprises a pushing means being operable by a resilient member and the movement means. This arrangement facilitates a simple mechanism with a small footprint.
  • the apparatus further comprises a second pusher element for indexing down the stack after the bottom-most cap or cap-strip is transferred over the reactor or reactor array; a first support means for supporting the stack while the bottom-most cap or cap-strip is transferred over the reactor or reactor array; and a second support means for supporting the cap or cap strip to substantially prevent tilting of the cap or cap strip while being transferred over the top opening of the reactor or reactor array.
  • the first support means comprises a first resilient gate for allowing the bottom-most cap or cap strip to move from the first support means to the second support means when the stack is pushed by the second pusher element, thereafter the first resilient gate returning to original configuration automatically to support the rest of the stack.
  • the second support means comprises a second resilient gate for allowing the first pusher element to push the cap or cap strip downwards to install, thereafter the second resilient gate returning to the original configuration automatically and before the second support means returns to original position below the first support means.
  • the apparatus comprises: a transfer means for transferring the bottom-most cap or cap strip over the reactor or reactor array respectively before the installation by the pressure means, wherein the pressure means, the transfer means and the releasing means are independently operable.
  • apparatus for amplifying nucleic acid.
  • the apparatus comprises sealing apparatus (SA) for sealing reactors with a cap each, the reactors being loaded with reaction material for processing nucleic acid by thermal processing, the reactors being in any form such as tubes or wellplates or chips or cartridges, the apparatus comprising: a pressure means for exerting pressure on the cap or a stack of the caps such that the cap or the bottom-most cap in the stack gets installed by press-fit on the reactor and in a pre-determined sequence for a plurality of reactors; and a thermal control module (TCM) for subjecting the at least one reactor from the SA to thermal processing for amplification of the nucleic acid.
  • SA sealing apparatus
  • TCM thermal control module
  • the cap may be a cap strip and the reactor may be a reactor array for batch processing.
  • the apparatus may further comprise a detection module (DM) for optical detection of the amplified nucleic acid from the TCM for analyses.
  • the apparatus may further comprise a sample preparation module (SPM) for processing nucleic acid materials or biological reaction materials containing nucleic acid and loading them into the reactors before the sealing apparatus (SA) is used to seal the reactor with a cap.
  • SA sealing apparatus
  • the integrated electro-mechanical apparatus allows a cost effective and time saving solution to integrate the SPM and the TCM by introducing the compact and automated SA in between, the advantages of which are described under the first aspect.
  • including the DM makes the apparatus complete right from extraction to analyses.
  • a second pressure means is provided for exerting pressure during the thermal processing and on the cap or the cap strip as installed on the reactor or the reactor array, for enhancing contact of the cap with the reactor and enhancing contact of the reactor with a heating means in the TCM.
  • the reactors may be positioned over at least one heating means within the TCM. This saves footprint and also the time to transfer the reactors from the SA to the TCM.
  • Fig. 1(a) presents a perspective views of a commercially available cap strip, a reactor array and a combined set of the two.
  • Fig. 1(b) presents a perspective view of a commercially available micro-well array.
  • Fig. 1(c) presents a cross-sectional view along the cut-line A- A' at Fig. 1(b).
  • Fig. 1(d) presents a perspective view of a commercially available wellplate with a matrix of the reactors or reactor arrays along with a commercially available and peel-off type adhesive film.
  • Fig. 1(e) presents Fig. 1(b), with the adhesive film as partially stuck over the reactors for sealing them as done in the art.
  • Fig. 2 is an isometric view of an embodiment of the apparatus according to an embodiment of the invention.
  • Fig. 3(a) is an isometric view of the sealing apparatus (SA) according to an embodiment of the invention.
  • Figs. 3(b) to 3(d) show cross sectional views of certain types of capping mechanism that the apparatus at Fig. 3(a) is capable of handling.
  • Fig. 4 is an isometric view of the cassette according to an embodiment of the invention.
  • Fig. 5 is an isometric interior view of the cassette at Fig. 4 accommodating a stack of cap strips, as according to an embodiment of the invention.
  • Fig. 6 is an isometric view of the cassette at Fig. 4, demonstrating the operation of a locking plunger as according to an embodiment of the invention.
  • Fig. 7 is an isometric view of the frame for operating the locking plunger of Fig. 6.
  • Fig. 8 is an isometric view of the frame in Fig. 7 when operating on the locking plunger of Fig. 6 as according to an embodiment of the invention.
  • Fig. 9 is an isometric view of the pusher for pushing down the stack of caps or cap strips in the cassette for releasing to install, as according to an embodiment of the invention.
  • Fig. 10 is a sectional elevation view demonstrating the operation of the pusher in Fig. 9 as according to an embodiment of the invention.
  • Fig. 11 is sectional elevation view of the tooth structure in the pawl bar of the pusher in Fig. 9 as according to an embodiment of the invention.
  • Fig. 12 in an elevation view demonstrates the operation of the pawl blocks of the pusher in Fig. 9 as according to an embodiment of the invention.
  • Fig. 13 in an elevation view demonstrates the operation of the pusher in Fig 9 along with the pawl blocks as according to an embodiment of the invention.
  • Figs. 14(a) and 14(b) in elevation view demonstrate the plate below the pawl bar in Fig. 9 and the angular movement of the plate over the stack as according to an embodiment of the invention.
  • Fig. 14(c) in an elevation view demonstrates installation of the bottom-most cap strip on the reactor strip under the angular movement of the plate over the stack as at Figs 14(a) and 14(b).
  • Figs. 15(a) to 15(c) in elevation view demonstrate the swinging movement of the plate over the stack when the plate is convex shaped as according to an embodiment of the invention.
  • Figs. 16(a) and 16(b) in elevation view demonstrate the plate below the pawl bar in Fig. 9 and the downward movement of the plate placed parallelly over the stack as according to an embodiment of the invention.
  • Fig. 17 is an isometric view of the cam motion with the motorized shaft operating on the frame of Fig. 7 and on the pusher of Fig. 9 as according to an embodiment of the invention.
  • Fig. 18 in an elevation view demonstrates how the rotation of the unlock cam sliding against the arm translates into a reciprocating motion of the unlock lever of Fig. 7 as according to an embodiment of the invention.
  • Fig. 19 in an elevation view demonstrates how a push cam operates the pusher of Fig. 9 to perform an indexing and pushing motion.
  • Fig. 20 in an isometric view illustrates the y-axis movement module of Fig. 3.
  • Fig. 21 in an isometric view illustrates the sealing apparatus using an actuator according to an alternate embodiment of the invention.
  • Fig. 22(a) shows the frame in Fig. 7 and Fig. 18, as operable by an actuator instead of the cam.
  • Fig. 22(b) is a partial view of Fig. 21, showing a pressure transducer as according to an embodiment of the invention.
  • Fig. 22(c) shows the cassette as at Fig. 4, when with the pressure transducer of Fig. 22(b), as according to an embodiment of the invention.
  • Fig. 22(d) shows a closer view of the pressure transducer as in Fig. 22(c).
  • Fig. 23 shows a hypothetical graph to represent the pressure sensed by the pressure transducer as at Fig. 22(b)
  • Fig. 24 shows a represents a full cycle of the SA of Fig. 3, Fig. 22(a) to 22(d).
  • Fig. 25 shows an embodiment where the stack of caps is positioned adjacent to the bottom surface instead of beneath.
  • Figs. 26(a) to (f) elaborates on the operation of the lower part of the Fig. 25.
  • Figs. 27(a) to (f) elaborates on the operation of the lower part of the Fig. 25 , according to an alternate embodiment.
  • Fig. 28 (a) and (b) are elevation cross-sectional view of an alternate embodiment for holding and releasing the stack of caps.
  • Fig. 29 (a) and (b) are elevation cross-sectional view of an alternate embodiment where, the first pusher, the second pusher and a motorized arm operate independent of each other.
  • Fig. 30 is a cross-sectional elevation diagram to show an embodiment where a vacuum- head picks up the cap strip for placement over the reactor array for the installation.
  • Fig. 31 (a) is a cross-sectional elevation diagram to show an embodiment where the cap strip is contacted with a liquid sealant before the installation.
  • Figs. 31 (b) to (d) is a cross-sectional elevation diagram to show use of the liquid sealant with the types of the capping mechanisms of Figs. 3(b) to 3(d).
  • Fig.32 shows an elevation cross-sectional view for an embodiment where the liquid sealant is layered along the top inner surface of the reactors.
  • Fig. 33 shows an elevation cross-sectional view for an embodiment where a rigid plate is placed and clamped over a heat block by two clamp tools at the edges.
  • Fig. 2 shows an integrated set-up of the apparatus for amplification of nucleic acid, with the sealing apparatus (SA) 100 being integrated with the sample preparation module (SPM) 200, the thermal control module (TCM) 300 and the optical detection module 400.
  • SA sealing apparatus
  • SPM sample preparation module
  • TCM thermal control module
  • PCR module is used interchangeably with the TCM 300 which includes other nucleic acid amplification processes such as isothermal amplification and primer extension.
  • the thermal processing in the TCM 300 includes thermocycling as well.
  • Fig. 3(a) shows an electro-mechanical SA 100 for installing the cap strip 2 onto the reactor strip 4 by press-fit in order to attain the combined set 6.
  • the SA module 100 may carry one or more cap strips 2, for stacking within the cap tray in the cassette 12.
  • the SA module 100 releases the cap strip 2, and installs the cap strip 2 onto the reactor strip 4 to cover up the reactors 5 in the reactor strip 4 after the reaction material with nucleic acid is loaded in the reactor strip 4.
  • the SA module 100 is able to continuously install cap strips 2 onto multiple reactor strips 4 one after the other. Once the stacked cap strips 2 are fully consumed in the cassette 12, a new stack of cap strips 2 may be manually refilled.
  • the cassette 12 is a removable item to house and release the cap strips 2 when required.
  • the frame 14 holds the cassette 12 and activates releasing movement of the cap strips 2 on the reactor strips 4.
  • a cap strip first pusher 18 performs indexing and pressing operation onto the cap strips 2 inside the cassette 12, for releasing and installing the cap strips 2 onto the reactor strips 4.
  • a motorized shaft 16 with multiple cams activates the motion for the frame 14 and the first pusher 18.
  • the Y-axis movement module 10 has a motorized stage to move the frame 14 horizontally for installing the cap strips 2 onto the reactor strips 4 serially.
  • the reactors 5 may be in the form of tubes or wellplates. Only one cassette 12 is shown, though according to other embodiments multiple cassettes 12 may be accommodated so that the sealing process can continue uninterrupted even when one or more cassettes need to be refilled with the stack.
  • the reactor strips 4 are positioned over the heating means 90 as shown.
  • the heating means 90 for thermal processing may be of any type as available in the art.
  • the press-fit mechanism applies to cases where under the pressure, a projected part 11 in the cap strip 2 gets engaged with the reactor 5 to seal the reactor 5 containing the reaction material (not shown).
  • the engagement may be internal or external or both.
  • the cap strips 2 move over the wellplate before the pressure is exerted for press-fit.
  • the wellplate may move under the cap strips 2.
  • Fig. 4 shows the cassette 12 with the locking plunger 20.
  • Fig. 5 shows an inner view of the cassette 12 as stacked with multiple pieces of cap strips 2.
  • the bottom surface 40 of the first pusher 18 as shown in Fig. 9 is also shown.
  • the bottom surface 40 pushes the stack of the cap strips 2 from the top as shown by the dashed arrow so that the bottom-most cap-strip 2 is released as shown by the dashed block arrow for installation on the reactor array 4 by press-fit.
  • the bottom surface 40 may move upwards to release the pressure on the stack so that the locking plunger 20 can hold the remaining stack inside the cassette 12.
  • Fig. 6 shows the cassette 12 when in a close-position and when in an open position, by operation of the locking plunger 20.
  • the locking plunger 20 has a lever 24 and a lid 26.
  • the lid 26 opens out as shown by the curved arrow to release the bottom most cap strip 2 in the direction shown by the dashed block arrow.
  • the locking plunger 20 resiliently restores back to the original position.
  • the pair of locking plunger 20 is hinged and pre-loaded with springs at bottom ends of the cassette 12, preventing the caps strips 2 from otherwise exiting the cap tray 22 from the bottom.
  • the bottom opening 25 of the cassette 12 is contoured to adequately fit the lateral shape of the cap strip 2 so that the position of the cap strip 2 within the cassette 12 is maintained fixed so as to align precisely over the reactors 5 when released.
  • the frame 14 has an arm 28, an unlock lever 30 and a housing 32 The housing 32 holds the cassette 12.
  • the unlock lever 30 is pre-loaded with a spring and can move up and down along housing 32. When the arm 28 on the unlock lever 30 is pushed, unlock lever 30 will move downwards. Once the arm 28 is released, the unlock lever 30 will resiliently return to position. When the arm 28 is pushed, the sloped contact 33 of the unlock lever 30 pushes against the lever 24 thereby opening the locking plunger 20.
  • FIG. 8 illustrates the assembly of the frame 14 and the cassette 12, wherein the sloped contact 33 push opens the lever 24 when the arm 28 is pushed downwards as shown by the dotted arrow.
  • the shape of the sloped contact 33 is useful in making firm contact with the lever 24 and sliding along the surface as the lever 24 operates.
  • FIG. 9 illustrates the operation of the first pusher 18.
  • a fixed pawl block 36 has a fixed position with reference to an axis guide 35, while a slider pawl block 38 slides up/down along the guide 35.
  • the fixed pawl block 36 is coupled together by a first spring 46.
  • the first spring 46 returns the slider pawl block 38 to its original position.
  • the first spring 46 creates a pull force whenever the slider pawl block 38 is pushed down from the fixed pawl block 36.
  • the pawl bar 34 is guided through both sets of the pawl blocks 36, 38.
  • the pawl bar 34 features a series of one-way tooth.
  • the tooth interacts with tip 50 of the second pawl finger 42, as described in Fig. 12 which illustrates how the second pawl finger 42 is pivoted and preloaded by a second spring 37.
  • the second spring 37 pushes the second pawl finger 42 against the pawl block 38, keeping it at the locked-position.
  • the tip 50 on the second pawl finger 42 is pushed, the second pawl finger 42 rotates along the first pivot 43 to the open-position. This operation results in a one way ratchet locking mechanism of the pawl finger 42.
  • Fig. 13 illustrates the performance of the pawl blocks 36, 38 and the pawl bar 34 performing indexing and pushing motion.
  • the cam follower 44 is attached on the slider pawl block 38.
  • the first pusher 18 is able to perform an indexing and pushing motion, as the slider pawl block 38 is pushed down.
  • the slider pawl block 38 keeps at lock position, hence pushing the tooth along the pawl bar 34.
  • the fixed pawl block 36 Upon pushing, the fixed pawl block 36 will open by the tooth on the pawl bar 34, to allow the pawl bar 34 to move downwards.
  • Fig. 14 illustrates the bottom press plate 40 pressing on a stack of cap strips 2 within the cassette 12.
  • the pawl bar 34 is able to keep traveling downwards to transfer a downward force for the installation of the cap strips 2.
  • the plate 40 is shown to be initially angularly placed over the stack at one edge on the right and thereafter pivotally rotated about the pivot 70 to place the left hand side on the stack as well, while the pawl bar 34 pushes downwards.
  • Fig. 14(c) shows how the cap strip 2 progressively gets installed on the reactor strip 4 from the right hand side to the left.
  • FIGs. 15(a) to (c) illustrate the mechanism described in Fig 14 but with the plate 40 being of convex shape for a more concentrated force exertion at the point of contact.
  • Fig. 16(a) and (b) illustrate the mechanism described in Figs 14 and 15 but with the plate 40 being of flat shape and while the pawl bar 34 pushes downwards without the pivotal rotation.
  • Fig. 17 illustrates the cam motion with the motorized shaft 16.
  • the rotation of the unlock cam 58 unlocks the locking plunger 20 and the rotation of the push cam 56 pushes down the first pusher 18.
  • the cams are coupled to the cam motor 54 to convert rotary motion to reciprocating motion.
  • Fig. 18 shows the unlock cam 58 sliding on the arm 28. As the unlock cam 58 rotates the contour surface will slide against the arm 28. As shown, from the initial position, the unlock lever 30 is pushed down to open the locking plunger 20. As illustrated, the unlock cam 30 is able to control the locking plunger 20 in different sections of the contour, such as initial, push unlock, hold open, and close the locking plunger 20.
  • Fig. 19 shows that the push cam 56 is in contact with the cam follower 44. As the push cam 56 rotates, the contour surface will slide against the cam follower 44 on the slider pawl block 38, which performs the action mentioned in Fig.9 where the pawl block 38 and pawl bar 34 performs indexing and pushing motion. The push cam 56 is then able to trigger motion in the first pusher 18 for indexing, pressing and installing the cap strips 2 onto the reactor strips 4. Thus the rotation of the push cam 56 drives the cap strips first pusher 18 to cause indexing and pressing motion.
  • Fig. 20 illustrates the y-axis movement module 10.
  • the module consists of a stage 62 and a motorized y-axis actuator 64.
  • the stage 62 will carry the rest of the SA 100 to move. Once a cap strip 2 is installed, it can move to another position to perform another installation.
  • the SA 100 cycles as follows: the SA 100 is parked into position, above a reactor strip 4.
  • the motorized shaft 16 then keeps rotating.
  • the cassette 12 unlocks and releases cap strip 2.
  • the released cap strip 2 is pushed by the first pusher 18 immediate after the release.
  • the bottom-most caps strip 2 will engage and install on to the reactor strip 4 positioned right below it.
  • the installation starts from one end as pre-described in Figs. 14 a to c.
  • the pusher 18 While the cassette 12 opens, the pusher 18 fully installs the bottom-most caps strips 2 onto the reactor strip 4 and thereafter fully indexes into the lock position. As the bottom-most cap strip 2 fully exits the cassette 12, the cassette 12 closes and returns to the locking position, thereby blocking the next cap strip 2 from exiting. The first pusher 18 then returns the slider pawl block 38 to position. Both the cassette 12 and first pusher 18 then restore to position. The next cap strip 2 then takes place of the bottom-most cap strip 2. The y-axis movement module 10 now moves the SA 100, to a new position, to install the new bottom-most cap strip 2 onto another reactor strip 4. [0094]
  • the material of the cap 3 may be transparent to light, with low auto fluorescence and compatible with the reaction in the reactors 5.
  • the cap 3 may be transparent to the light to measure fluorescence emission of the reaction material 21 inside the reactor 5.
  • the cap 3 may be made of rubbery, pierceable and self-closing material like silicone, thereby allowing a needle-like object to penetrate to dispense and aspire liquid into and out of the tubes during and after the PCR, for more complex assays like nested PCR and library preparation in next-generation sequencing protocols.
  • the material of the cap 3 may be suitable for subsequently undergoing the thermal processing under various heating or cooling methods such as by infrared, induction, thermoelectric coolers, water bath and the kind.
  • the temperatures that the material of the cap 3 will be subjected to may typically be 10 degree Celsius to 500 degree Celsius to accommodate a wide range of temperatures under the thermal processing.
  • Figs. 21 and 22(a) show an alternate embodiment of the SA 100 using a first actuator 82 for the first pusher 18 and the second actuator 84 for the frame in Fig. 7 and Fig. 18.
  • the first actuator 82 and the second actuator 84 replace the push cam 56 and the unlock cam 58 described earlier.
  • Fig. 22(b) is a partial view of Fig. 21 , showing a pressure transducer 86 located under the plate 40 according to an embodiment.
  • Fig. 22(c) shows the cassette as at Fig. 4, when with the pressure transducer 86 of Fig. 22(b).
  • Fig. 22(d) shows a closer view of the pressure transducer as in Fig. 22(b) and 22(c).
  • the pressure transducer 86 monitors the pressure exerted by the plate on the cap 3 or the cap strip 2 or the stack. Once the installation is complete on the reactor 5 or the reactor array 4, the plate 40 can no more move downwards and then the pressure sensed increases significantly.
  • Fig. 23 shows a hypothetical graph to represent the pressure sensed by the pressure transducer as at Fig. 22(b).
  • the Region- 1 represents the time when the bottom-most cap 3 or cap strip 2 is moving downward to approach the reactor 5 or the reactor array 4.
  • the pressure is low and near-constant now.
  • the Region-2 represents the time when the bottom-most cap 3 or cap strip 2 makes contact with the reactor 5 or the reactor array 4 and starts engaging together.
  • the pressure now increases, as shown by the increasing slope.
  • the Region-3 represents the time when the bottom-most cap 3 or cap strip 2 is completely engaged with the reactor 5 or the reactor array 4 and the installation is complete.
  • the pressure now increases significantly as the plate 40 can no more move downwards, as shown by the steeper slope.
  • a controller (not shown) receives the electric signal from the pressure transducer 86 and coordinates with the first actuator 82 and the second actuator 84 to synchronize their respective operations with regards to the releasing and the installation function.
  • Fig. 24 represents a sequence of operation of the SA 100 of Fig. 3 and Fig. 22(a) to 22(e).
  • the y-axis movement module 10 holds the SA 100 at the initial position.
  • the y-axis movement module 10 moves the SA 100 to a predetermined new position.
  • the cassette 12 then unlocks the plunger 20 and releases the bottom-most cap strip 2 while the first pusher 18 pushes the stack such that the bottom-most cap strip 2 gets installed into the reactor strip 4.
  • the first pusher 18 moves up to release the push and the cassette 12 closes to block the next cap strip 2 from getting released.
  • the position of the pusher 18 and the configuration of the cassette 12 are restored and the SA is ready for a new cycle.
  • the reactor 5 or the reactor array 4 may be pushed upwards against the cap 3 or the cap strip 2 for installation of the cap 3 or the cap strip 2 by the press-fit.
  • An alternate embodiment is shown in Fig. 25.
  • the stack of caps 3 is positioned adjacent to the bottom surface 40, instead of beneath as described earlier.
  • the stack rests on the resting plate 81.
  • the guard 80 helps the cap 3 from falling out of the otherwise open end.
  • the stack above the bottom-most cap 3 or cap strip 2 is secured in position by a holder 51.
  • the transfer lever 52 is usable for transferring the bottom-most cap 3 or cap strip 2 over the reactor 5 or reactor array 4 before the installation by the bottom surface 40.
  • the pusher cam 60 and the transfer cam 66 are both rotated by the same motor 68.
  • the pusher cam 60 provides a reciprocating motion to the first pusher 18 along the vertical direction (as shown by the vertical dotted arrow).
  • the first pusher 18 is held vertically by the first guide 72.
  • the transfer cam 66 provides reciprocating motion in a vertical direction (as shown by the vertical dashed arrow) to the transfer lever 52 which in turn provides reciprocating motion of the transfer bracket 78 in the horizontal direction (as shown by the horizontal arrow) with the aid of the spring 76.
  • the transfer lever 52 is held vertically by the second guide 74.
  • the stack of caps 3 or cap strip 2 move downwards under gravity and without any pressure from the top of the stack.
  • the holder 51 may be internally contoured to adequately fit the lateral shape of the cap 3 or cap strip 2 so that the position of the cap 3 or the cap strip 2 within the holder 51 is maintained fixed so as to align precisely over the reactors 5 when released.
  • a second pusher may be used to push down the stack for releasing the bottom most cap 3 or cap strip 2.
  • Figs 26 (a) to (f) describe the operation of the lower part of the Fig. 25 in more detail.
  • FIG. 26(a) represents an initial position where the holder 51 is holding the stack in position and the lower most cap 3 is facing the transfer bracket 78.
  • the bottom surface 40 now is suspended above the unsealed reactor 5 with a gap between the two.
  • Fig, 26(b) represents the stage when due to the rotation of the motor 68, the transfer cam 66 pushes the transfer lever 52 downwards. This causes the transfer bracket 78 to push the bottom-most cap 3 horizontally to position over the reactor 5 while compressing the spring 76.
  • a motorized plunger (not shown) may also be used instead of the transfer bracket 78.
  • Fig. 26(c) shows when the bottom-most cap 3 is positioned over the reactor 5. In Fig.
  • Fig. 26(d) due to the rotation of the motor 68, the pusher cam 60 pushes the first pusher 18 downwards such that the bottom surface 40 makes contact with the bottom-most cap 3 as over the reactor 5 to start the installation.
  • the cap 3 shown in dashed lines is after installation.
  • Fig. 26 (e) illustrates the status when the installation is complete and the first pusher 18 has gone upwards to the initial position and the transfer bracket 78 has retracted to the original position due to the transfer lever 52 having gone upwards as well thereby releasing the spring 76.
  • the sealed reactor 5 is moved to another location (not shown) and an unsealed reactor 5 is moved to the position below the bottom surface 40 for the installation.
  • the stack After the transfer bracket 78 has retracted, the stack has automatically moved downwards under gravity so that a new cap 3 now forms the bottom-most cap 3.
  • This embodiment of letting the stack move downwards only under gravity and without any external pressure prevents the caps 3 or cap strips 2 from getting deformed before installation thereby causing reliability issues with the installation. Such deformation may occur with some types of commercially available caps 3 or cap-strips 2 with higher flexibility.
  • Fig. 27 (a) to (f) illustrate an alternate embodiment, where the apparatus further comprises a second pusher 91 for indexing down the stack every time the bottom-most cap 3 is transferred over the reactor 5.
  • a first support 92 supports the stack while the bottom-most cap 3 is transferred over the reactor 5.
  • the second support 93 provides the transfer of the cap 3 without letting it get tilted particularly on reaching the top opening of the reactor 5.
  • the spring loaded first gate 94 in the first support 92 allows the bottom-most cap 3 to move from the first support 92 to the second support 93 when the stack is pushed downwards by the second pusher 91.
  • the spring loaded second gate 95 in the second support 93 allows the bottom-most cap 3 as positioned over the reactor 5 to be installed by the first pusher 18.
  • the stack is shown to be supported by the first support 92.
  • the dashed block arrow indicates that the stack is pushed downwards by the second pusher 91 thereby causing the spring loaded first gate 94 to open outwards as indicated by the dashed line arrows.
  • the spring loaded first gate 94 goes back to the original configuration and the rest of the stack is again supported by the first support 92.
  • the bottom-most cap 3 at the second support 93 is now transferred by the transfer bracket 78 to be positioned over the reactor 5 for installation by the first pusher 18.
  • the first pusher 18 pushes the cap 3 downwards to install, through the spring loaded second gate 95 which open outwards as shown by the dashed line arrows.
  • the first pusher 18 moves upwards as shown by the dashed block arrow and the second gate 95 automatically reverts to the original configuration as shown by the dashed line arrows.
  • the second support 93 would return to the original configuration automatically and the second support 93 returns to its starting position below the first support 92.
  • the resilience of the cap 3 or the holder 51 may also allow the release of the bottom most cap 3 or cap strip 2 one at a time under the pressure of the second pusher 91 and without engagement of the spring loaded first gate 94 or the spring loaded second gate 95.
  • the reactors 5 may be in the form of tubes 5 as in Fig. la or wellplates 7 as in Fig. lb with liquid access ports that require sealing before the thermal processing.
  • the reactor 5 may also be in the form of PCR chips and PCR cartridges, both of which have inlet and outlet ports that need to be sealed before thermal processing.
  • Fig. 28 (a) shows yet another embodiment where flexible holders 94 (a) hold the stack of caps 3.
  • Fig. 28 (b) shows that during operation, as the second pusher 91 presses the stack downwards, the bottom-most cap 3 gets released by the flexible holders 94(a) so as to rest on the second support 93 as in Fig. 27 (a) for being transferred over the reactor 5 for installation.
  • the reactor 5 is shown to contain the reaction material 21.
  • Figs. 29 (a) and (b) shows an embodiment where the released cap 3 is being transferred over the reactor 5 by a motorized arm 78 (a).
  • the first pusher 18, the second pusher 91 and the motorized arm 78 (a) operate independent of each other.
  • Such an embodiment may provide enhanced reliability and a simplified mechanism provides more flexibility to the control of their movements.
  • a pressure block 41 has a vacuum- head 39 that picks up the top-most cap strip 2 from the stack and as shown by the dashed block arrow, places over the reactor array 4 for the installation.
  • the pressure block 41 presses the cap strip 2 downwards so that the projected part in the cap strip 2 gets engaged with the reactor array 4 to seal the reactors 5.
  • a separate arm for the picking and placing may be used.
  • Fig. 31 (a) shows an embodiment where the cap strip 2 is contacted with a liquid sealant 3a in a sealant bath 3b before the installation. Figs.
  • FIG. 31 (b) to (d) show use of the liquid sealant 3a with the types of the capping mechanisms of Figs. 3(b) to 3(d).
  • the layer of the liquid sealant 3a when in contact with the surface of the reactor 5 helps in an improved sealing and also helps as a lubricant during the installation. Since the reaction material 21 inside the reactors 5 get exposed to the liquid sealant 3a, the liquid sealant 3a needs to be compatible with the reaction material 21.
  • a compatible liquid sealant 3a may be any of a high viscosity silicone material such as PDMS (polydimethyl siloxane) namely Sylgard 184, a Dow Corning Corporation product, an oil, glue and any other polymer.
  • PDMS polydimethyl siloxane
  • the liquid sealant 3a is layered along the top inner surface of the reactors 5 which reduces contamination of lubricant to other reactors 5 and users during storage and handling.
  • the sealant applicator 3b is partially dipped in the sealant 78sealant 3a before the process of sealing. Alternately, the liquid sealant 3a may be placed manually.
  • the top inner surface of the reactor 5 or the protruded portion of the cap 3 may be pre-coated with the sealant 3a. The sealant may remain viscous or solidify at a later time.
  • a rigid plate 2a is placed over the cap strip 2 and clamped to a heat block 2c by two clamp tools 2b at the edges after the step of sealing and before the thermal processing.
  • Any other suitable method of clamping may also be used.
  • the clamping may also be done with a reactor holder for holding the reactors 5 during thermal processing (not shown).
  • the clamp tools 2b may be removed after the reactor array 4 is cooled down to avoid popping out of the cap strips 2 under the vapor pressure.
  • a dry sealant such as when the liquid sealant 3a is of a type that solidifies during the subsequent thermal processes such as thermal cycling may not raise this issue under vapor pressure.
  • a liquid such as an oil (not shown) may be used in the gap between the cap 3 and the reaction material 21 to further assist in retarding the evaporation from the reaction material 21 during the thermal processing.
  • the invention is applicable to any reactor 5 design which is capable of being sealed by the press-fit mechanism described herein.
  • the invention is also applicable to simultaneous installation of multiple cap strips 2 on a plurality of reactor arrays 4 or wellplate 7.
  • the cap 3 or the cap strip 2 may be at one edge pre-attached to the reactor 5 or the reactor array 4 respectively. During the sealing procedure under the invention, the cap 3 or the cap strip 2 needs to be positioned over the reactor 5 or the reactor array 4 respectively before the installation.

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Abstract

La présente invention concerne un appareil pour sceller des réacteurs en installant un capuchon dans chaque réacteur. Les réacteurs peuvent être chargés avec un matériau de réaction pour le traitement thermique d'acide nucléique. L'appareil comprend un moyen de pression pour exercer une pression sur un capuchon ou un empilement des capuchons de sorte qu'une partie saillante dans le capuchon ou le capuchon inférieur dans l'empilement soit installé dans le réacteur par ajustement serré.
PCT/SG2018/050121 2017-03-20 2018-03-19 Appareil d'amplification d'acides nucléiques WO2018174818A1 (fr)

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SG10201702235TA SG10201702235TA (en) 2017-03-20 2017-03-20 Apparatus for amplification of nucleic acids
SG10201702235T 2017-03-20

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Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN109294868A (zh) * 2018-09-28 2019-02-01 杨帆 一种生物反应容器上样装置
WO2022107604A1 (fr) * 2020-11-19 2022-05-27 横河電機株式会社 Dispositif de traitement, système d'extraction d'acides nucléiques et système d'analyse d'acides nucléiques

Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE2424595A1 (de) * 1974-05-21 1975-12-04 Benz & Hilgers Gmbh Vorrichtung zum vereinzeln und aufbringen des jeweils untersten, gestapelten kunststoffdeckels auf einen behaelter
US20080286151A1 (en) * 1999-12-21 2008-11-20 Cepheid Apparatus for performing heat-exchanging chemical reactions
JP2010036949A (ja) * 2008-08-04 2010-02-18 Toko Kikai:Kk 食品容器の被蓋装置
US20100303690A1 (en) * 2007-09-06 2010-12-02 James Richard Howell Thermal control apparatus for chemical and biochemical reactions
US9079757B2 (en) * 2011-08-02 2015-07-14 3M Innovative Properties Company Cap handling tool and method of use
US20160310943A1 (en) * 2013-12-20 2016-10-27 Hamilton Bonaduz Ag Covering device, in particular lid, for covering reaction vessels

Patent Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE2424595A1 (de) * 1974-05-21 1975-12-04 Benz & Hilgers Gmbh Vorrichtung zum vereinzeln und aufbringen des jeweils untersten, gestapelten kunststoffdeckels auf einen behaelter
US20080286151A1 (en) * 1999-12-21 2008-11-20 Cepheid Apparatus for performing heat-exchanging chemical reactions
US20100303690A1 (en) * 2007-09-06 2010-12-02 James Richard Howell Thermal control apparatus for chemical and biochemical reactions
JP2010036949A (ja) * 2008-08-04 2010-02-18 Toko Kikai:Kk 食品容器の被蓋装置
US9079757B2 (en) * 2011-08-02 2015-07-14 3M Innovative Properties Company Cap handling tool and method of use
US20160310943A1 (en) * 2013-12-20 2016-10-27 Hamilton Bonaduz Ag Covering device, in particular lid, for covering reaction vessels

Cited By (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN109294868A (zh) * 2018-09-28 2019-02-01 杨帆 一种生物反应容器上样装置
WO2022107604A1 (fr) * 2020-11-19 2022-05-27 横河電機株式会社 Dispositif de traitement, système d'extraction d'acides nucléiques et système d'analyse d'acides nucléiques
JP2022081170A (ja) * 2020-11-19 2022-05-31 横河電機株式会社 処理装置、核酸抽出システム、核酸分析システム
JP7327360B2 (ja) 2020-11-19 2023-08-16 横河電機株式会社 熱処理システム、核酸抽出システム、核酸分析システム

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