EP3349902B1 - System zur biologischen analyse - Google Patents
System zur biologischen analyse Download PDFInfo
- Publication number
- EP3349902B1 EP3349902B1 EP16775921.6A EP16775921A EP3349902B1 EP 3349902 B1 EP3349902 B1 EP 3349902B1 EP 16775921 A EP16775921 A EP 16775921A EP 3349902 B1 EP3349902 B1 EP 3349902B1
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- European Patent Office
- Prior art keywords
- sample
- thermal
- sample block
- block
- heating
- Prior art date
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- 238000004458 analytical method Methods 0.000 title claims description 12
- 238000001816 cooling Methods 0.000 claims description 25
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- 239000000463 material Substances 0.000 claims description 4
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- 230000007246 mechanism Effects 0.000 description 18
- 238000003752 polymerase chain reaction Methods 0.000 description 11
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Images
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
- B01L2200/00—Solutions for specific problems relating to chemical or physical laboratory apparatus
- B01L2200/02—Adapting objects or devices to another
- B01L2200/025—Align devices or objects to ensure defined positions relative to each other
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
- B01L2200/00—Solutions for specific problems relating to chemical or physical laboratory apparatus
- B01L2200/04—Exchange or ejection of cartridges, containers or reservoirs
-
- 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
- B01L2200/141—Preventing contamination, tampering
-
- 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
- B01L2300/06—Auxiliary integrated devices, integrated components
- B01L2300/0627—Sensor or part of a sensor is integrated
- B01L2300/0663—Whole 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
- B01L2300/1822—Conductive heating, heat from thermostatted solids is conducted to receptacles, e.g. heating plates, blocks using Peltier elements
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
- B01L2300/00—Additional constructional details
- B01L2300/18—Means for temperature control
- B01L2300/1894—Cooling means; Cryo cooling
Definitions
- the present invention relates generally to systems and methods for biological analysis, and more particularly, to thermal cyclers and methods of using same.
- thermo cyclers or thermocycling devices and are used to generate specific temperature cycles, i.e. to set predetermined temperatures in the reaction vessels to be maintained for predetermined intervals of time.
- the chemical reaction has an optimum temperature for each of its stages and as such less time spent at non-optimum temperatures means a better chemical result is achieved.
- a minimum time is usually required at any given set point which sets a minimum cycle time and any time spent in transition between set points adds to this minimum time. Since the number of cycles is usually quite large, this transition time can significantly add to the total time needed to complete the amplification.
- the samples in the various wells experience similar changes in temperature. Temperature gradients often exist within thermal block assembly, causing some samples to have different temperatures than others at particular times in the cycle. Further, there are delays in transferring heat from the heating and cooling elements, sample block, and samples, and those delays may differ across the sample block. These differences in temperature and delays in heat transfer cause the yield of the PCR process to differ from sample to sample depending on the location of the sample in the sample block. Differences in the yield form the PCR process that result from the location of the sample in the sample block can decrease the reliability of the data obtained from the PCR reaction. Additionally, irregularities in the heat sink can produce deviations in the heating and cooling of the sample block.
- US2011/0151519 A1 describes a laboratory apparatus, in particular for performing a polymerase chain reaction (PCR) in a plurality of PCR-samples, which comprises an arrangement for tempering samples.
- the arrangement comprises a tempering block for the tempering of samples, the tempering block comprising a reception side, which provides receptacles for receiving sample vessels, and a contact side for the contact of at least one tempering device.
- a temperature measurement device may be assigned to a tempering device.
- the sample block includes a lower surface configured to be thermally coupled to the heating and cooling element, the lower surface including one or more slots.
- the thermal block assembly further includes one or more temperature sensors configured to extend through the one or more slots of the lower surface of the sample block and one or more thermal pads between the one or more temperature sensors and heating and cooling element.
- the one or more thermal pads are made of a material that has a lower thermal conductivity than the sample block.
- Thermal cycler system 10 includes a drip pan 12, which includes an ejection mechanism (discussed further below), and a thermal block assembly 14, as shown in FIG. 4 .
- the drip pan 12 seals the components of thermal block assembly 14 from environmental conditions above the drip pan 12.
- thermal block assembly 14 includes a sample block assembly 16, a heating and cooling element 18, and a heat exchanger or heat sink 24.
- the sample block assembly 16 includes a sample block 20 and a sample holder 22 (shown in FIGS. 12A and 12B ).
- the sample block 20 includes a plurality of cavities 26 and is configured to be loaded with the correspondingly shaped sample holder 22 containing a plurality of biological or biochemical samples in a plurality of wells 28. More details of thermal cycler system 10 are discussed below.
- the heating and cooling element 18 of thermal block assembly 14 is shown in more detail.
- the heating and cooling element 18 is used to uniformly heat and cool the sample block 20, which transfers heat to and from the samples in the wells 28 of the sample holder 22.
- the heating and cooling element 18 may include thermoelectric devices 32 such as, for example, Peltier devices. Although the heating and cooling element 18 is shown as including six thermoelectric devices 32, it should be recognized that the number of thermoelectric devices 32 may vary depending on a number of factors including, but not limited to, cost, the number of independent zones desired, and the size of the sample block 20.
- the heat sink 24 of thermal block assembly 14 is shown in more detail.
- the heat sink 24 includes projections, such as posts or ridges, to secure the position of thermoelectric devices 32 relative to the heat sink 24.
- the heat sink 24 includes ridges 34 arranged in rows and columns.
- the rows of ridges 34 are aligned with the space between the adjacent thermoelectric devices 32.
- the ridges 34 are configured to extend through the heating and cooling element 18 and to engage the adjacent edges 36 of the individual thermoelectric devices 32.
- the number and the configuration of the ridges 34 may be adjusted.
- the ridges 34 do not introduce significant irregularities in the heat distribution between the heat sink 24 and the thermoelectric devices 32 because the ridges 34 engage the adjacent edges 36 rather than the surfaces of thermoelectric devices 32.
- the heat sink 24 also includes ridges 38 arranged around a peripheral edge 40 of the heat sink 24. The ridges 38 are configured to engage a peripheral edge 42 of the heating and cooling element 18. In this arrangement, the ridges 34, 38 secure the position of the heating and cooling element 18 relative to the heat sink 24 while preserving the uniformity of the heat distribution.
- the heating and cooling element 18 is thermally coupled to the heat sink 24 by a thermally conductive material 44.
- the thermally conductive material 44 has substantially the same dimensions as the heating and cooling element 18 and includes openings 46.
- the openings 46 are configured to align with the ridges 34 when the thermally conductive material 44 is positioned on the heat sink 24.
- the ridges 34 extend through the openings 46 of the thermally conductive material 44 and the space between the adjacent thermoelectric devices 32 (as shown best in FIG. 12B ).
- the thermally conductive material 44 improves the heat distribution between the heating and cooling element 18 and the heat sink 24.
- the thermally conductive material 44 may include, for example, a thermally conductive phase change material coated on each side of the thermally conductive material 44.
- the heating and cooling element 18 is thermally coupled to the sample block 20 via a phase change layer 48.
- the phase change layer 48 can either be a single element having substantially the same dimensions as the heating and cooling element 18, or can be multiple elements each having substantially the same dimensions as the individual thermoelectric devices 32 of the multiple block design.
- the phase change layer 48 includes six elements corresponding to the six thermoelectric devices 32. Utilizing multiple elements of the phase change layer 48 aids in preventing excess phase change material from flowing between the thermoelectric devices 32.
- the phase change layer 48 may be made of a foil coated with a thermally conductive phase change material.
- the foil may be aluminum.
- the sample block 20 may have a plurality of cavities 26 configured to receive a plurality of correspondingly shaped wells 28 of the sample holder 22.
- the wells 28 are configured to receive a plurality of samples, wherein the wells 28 may be sealed within the sample holder 22 via a lid, cap, sealing film or other sealing mechanism between the wells 28 and the heated cover.
- the sample block 20 includes 384 cavities 26.
- the sample holder 22 may be a 384-well microtiter plate. It should be recognized that the sample block assembly 16 may have alternate configurations.
- the sample holder 22 may be, but is not limited to, any size multi-well plate, card or array including, but not limited to, a 24-well microtiter plate, 50-well microtiter plate, a 96-well microtiter plate, a microcard, a through-hole array, or a substantially planar holder, such as a glass or plastic slide.
- the wells 28 in various embodiments of a sample holder 22 may include depressions, indentations, ridges, and combinations thereof, patterned in regular or irregular arrays formed on the surface of the sample holder 22.
- Sample or reaction volumes can also be located within wells or indentations formed in a substrate, spots of solution distributed on the surface a substrate, or other types of reaction chambers or formats, such as samples or solutions located within test sites or volumes of a microfluidic system, or within or on small beads or spheres.
- Samples held within the wells 28 may include one or more of at least one target nucleic acid sequence, at least one primer, at least one buffer, at least one nucleotide, at least one enzyme, at least one detergent, at least one blocking agent, or at least one dye, marker, and/or probe suitable for detecting a target or reference nucleic acid sequence.
- the sample block 20 can be fixed, or clamped, to other components of the thermal block assembly 14 such as, for example, the heat sink 24.
- the sample block 20 can be floating.
- the floating sample block 20 may sit on a provided flat surface or surfaces to keep the sample block 20 substantially aligned with the other components of thermal block assembly 14.
- the floating sample block 20 can move laterally at all sides. Generally, such movement will be limited to prevent the sample block 20 from becoming misaligned with, for example, thermoelectric devices 32, the heat sink 24 and/or the heated cover.
- the assembly may provide, for example, an abutment (not shown) that constrains the lateral movement. Movement can be restrained, for example, to 1 mm at all sides. By allowing such constrained lateral movement, the floating block can adjust to any stacked up tolerances and misalignment that the block may have to the heated cover.
- the illustrated thermal block assembly 14 includes a floating heater 50 and temperature sensors 52.
- the floating heater 50 may be located along an exterior perimeter ledge 54 of an underside 56 of the sample block 20.
- the floating heater 50 is used to offset colder temperatures near the cavities 26 around the perimeter of the sample block 20 as compared to more centrally located cavities 26.
- the floating heater 50 can be a Kapton heater with one side coated with aluminum foil.
- the temperature sensors 52 are used to detect the temperature of the sample block 20 at discrete distances along the length thereof. The readings from the temperature sensors 52 provide insight into the heat distribution between the sample block 20 and the heat sink 24.
- each temperature sensor 52 is positioned in a slot 58 in the underside 56 of the sample block 20.
- each temperature sensor 52 is accompanied by a thermal interface pad 60.
- the thermal interface pads 60 may also act as a shock absorber between thermoelectric devices 32 and the temperature sensors 52.
- the thermal interface pads 60 are positioned adjacent to the temperature sensors 52 in the slots 58 and are flush with the underside 56 of the sample block 20.
- the thermal interface pads 60 may have a tacky or adhesive-like surface such that the temperature sensors 52 are generally held in place during assembly.
- the thermal interface pads 60 are made of a material that has a lower thermal conductivity than the sample block 20.An exemplary suitable material is Gap Pad VO from Bergquist Company. As shown in FIG. 8 , the thermal interface pads 60 may not extend the entirety of the length of each slot 58. The portion of the slot 58 not occupied by the temperature sensor 52 and the thermal interface pad 60 may be filled with a thermally conductive compound, such as thermal grease. Together, the temperature sensors 52 and the thermal interface pads 60 allow for detection of the heat distribution along the sample block 20 with reduced interference in the heat distribution caused by the temperature sensors 52 and the slots 58.
- thermal cycler system 10 includes the drip pan 12, which is placed over the sample block 20.
- the drip pan 12 along with an optional seal or gasket 62 (shown in FIGS. 12A and 12B ), forms a seal between the sample block 20 and the drip pan 12 to isolate thermoelectric devices 32 from environmental conditions above the sample block 20 and the drip pan 12 with the wells 28 received in the cavities 26.
- the drip pan 12 prevents any sample that may splash out of the wells 28 from reaching the sensitive electronic components of the thermal block assembly 14.
- the sample holder 22 is positioned over the sample block 20 and the drip pan 12.
- a heated cover may provide a downward force to the sample holder 22.
- the downward force provides vertical compression between the sample block assembly 16 and the other components of thermal block assembly 14, which improves thermal contact between the sample block 20 and the sample holder 22 to heat and cool the samples in the wells 28.
- the heated cover may also prevent or minimize condensation and evaporation above the samples contained in the wells 28, which can help to maintain optical access to samples.
- the user typically pulls the sample holder 22 away from the sample block 20, which requires some force in order to release it. The force needed to remove the sample holder 22 may result in samples being spilled.
- the drip pan 12 includes an ejection mechanism 64.
- the ejection mechanism 64 includes caps 66, which each include two springs 68 and a cap cover 70.
- the drip pan 12 includes housings 72 that engage the caps 66.
- Each housing 72 includes a ledge 74 having two posts 80 on which the springs 68 are positioned.
- the springs 68 include a first end 76 and a second end 78.
- the first ends 76 of the springs 68 are engaged with the posts 80, thus securing the position of the springs 68 relative to the housing 72.
- the second ends 78 of the springs 68 engage the cap cover 70 when the caps 66 move between an engaged position and an unengaged position (discussed further below).
- the housing 72 further includes a shoulder 82, and the cap cover includes an outer edge 84.
- the shoulder 82 is configured to engage the outer edge 84 and prevents the outer edge 84 from moving beyond the shoulder 82.
- each cap 66 may have an engaged position and an unengaged position.
- FIGS. 12A and 12B illustrate an engaged, or compressed, position of a cap 66 that occurs when the heated cover (not shown) presses the sample holder 22 against the sample block 20.
- heated cover provides a downward force against the sample holder 22
- the sample holder 22 depresses the cap cover 70 (i.e., moves the cap cover 70 toward the ledge 74) causing the springs 68 to compress.
- the downward force from the heated cover to hold the sample holder 22 against the sample block 20 is removed. Referring to FIGS.
- FIG. 13A and 13B an unengaged, or extended, position of a cap 66 is shown where the sample holder 22 is raised from the sample block 20. Once the downward force from the heated cover is removed, the caps 66 eject the sample holder 22. As the springs 68 lengthen, the cap cover 70 moves away from the ledge 74 and the outer edge 84 of the cap cover 70 engages the shoulder 82. The removal of the sample holder 22 by the user now requires less force due to the separation between the sample holder 22 and the drip pan 12. Because of the increased ease of removal, there is a reduced risk of spilling the samples from the wells 28.
- each spring 68 may have a force of about 0.4 kgf to about 0.5 kgf, meaning each cap 66 would have a force of about 0.8 kgf to about 1.0 kgf. Where a total of four caps 66 are included in the drip pan 12, a total force of about 3.2 kgf to about 4.0 kgf will be available to eject heated cover.
- the ejection mechanism 86 includes two ejector plates 88, which each include two springs 90.
- the ejection mechanism 86 may be coupled to a drip pan 92 via shoulder screws 94.
- a drip pan 92 includes recesses 96 that correspond to the ejector plates 88. Ends of the springs 90 engage the ejector plates 88 when the ejector plates 88 move between an engaged or compressed position and an unengaged or expanded position (discussed further below).
- the shoulder screws 94 are configured to engage a portion of the ejector plates 88 and prevent the ejector plates 88 from moving beyond the unengaged position.
- FIG. 15A illustrates the engaged, or compressed, position of an ejector plate 88 that occurs when the heated cover (not shown) presses the sample holder 22 against the sample block 20.
- the heated cover provides a downward force against the sample holder 22
- the sample holder 22 depresses the ejector plate 88 (i.e., moves the ejector plate 88 in a direction toward a ledge 98 of the drip pan) causing the springs 90 to compress.
- the downward force from the heated cover to hold the sample holder 22 against the sample block 20 is removed. Referring to FIG.
- the unengaged, or extended, position of an ejector plate 88 is shown where the sample holder 22 is raised from the sample block 20. Once the downward force from the heated cover is removed, the ejector plate 88 ejects the sample holder 22. As the springs 90 lengthen, the ejector plate 88 moves away from the ledge 98 and a portion of the ejector plate 88 engages the shoulder screws 94. The removal of the sample holder 22 by the user now requires less force due to the separation between the sample holder 22 and the drip pan 92. In one embodiment, the springs 90 may extend the ejector plates 88 a distance of 2 mm from the engaged position to the disengaged position. Because of the increased ease of removal, there is a reduced risk of spilling the samples from the wells 28.
- thermal cycler system 10 may include a variety of other modules and systems to perform thermal cycling.
- thermal cycler system 10 may include an optical system.
- the optical system may have an illumination source that emits electromagnetic energy, an optical sensor, detector, or imager, for receiving electromagnetic energy from samples in the sample holder 22, and optics used to guide the electromagnetic energy from each DNA sample to the imager.
- Thermal cycler system 10 may further include a control system and/or a computer system capable of controlling the operation of thermal cycler system 10.
- Embodiments of the present invention may be applicable to any PCR process, experiment, assay, or protocol where a large number of samples or solutions test volumes are processed, observed, and/or measured.
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- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Biochemistry (AREA)
- General Health & Medical Sciences (AREA)
- Molecular Biology (AREA)
- Clinical Laboratory Science (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Apparatus Associated With Microorganisms And Enzymes (AREA)
- Automatic Analysis And Handling Materials Therefor (AREA)
- Measuring Or Testing Involving Enzymes Or Micro-Organisms (AREA)
Claims (4)
- Thermoblockanordnung (14) zur Verwendung in einem System für biologische Analyse, umfassend: ein Heiz- und Kühlelement (18);
einen Probenblock (20), der eine obere Oberfläche mit einem oder mehreren Hohlräumen aufweist, die konfiguriert sind, um einen Probenhalter (22) aufzunehmen, wobei der Probenblock (20) eine untere Oberfläche beinhaltet, die konfiguriert ist, um mit dem Heiz- und Kühlelement (18) thermisch gekoppelt zu sein, wobei die untere Oberfläche einen oder mehrere Schlitze (58) beinhaltet;
einen oder mehrere Temperatursensoren (52), die konfiguriert sind, um sich durch den einen oder die mehreren Schlitze (58) der unteren Oberfläche des Probenblocks (20) zu erstrecken; und
ein oder mehrere Wärmeleitpads (60) zwischen dem einen oder den mehreren Temperatursensoren (52) und dem Heiz- und Kühlelement (18), wobei das eine oder die mehreren Wärmeleitpads (60) aus einem Material hergestellt sind, das eine geringere Wärmeleitfähigkeit als der Probenblock (20) aufweist. - Thermoblockanordnung (14) nach Anspruch 1, wobei das eine oder die mehreren Wärmeleitpads (60) in den Schlitzen angrenzend an den einen oder die mehreren Temperatursensoren (52) positioniert sind.
- Thermoblockanordnung (14) nach einem der vorhergehenden Ansprüche, wobei der Probenblock (20) 384 Hohlräume aufweist.
- System für biologische Analyse (10), umfassend eine Thermoblockanordnung (14) nach einem der vorhergehenden Ansprüche.
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US201562218948P | 2015-09-15 | 2015-09-15 | |
US201562270975P | 2015-12-22 | 2015-12-22 | |
PCT/US2016/051983 WO2017048987A1 (en) | 2015-09-15 | 2016-09-15 | Systems and methods for biological analysis |
Publications (2)
Publication Number | Publication Date |
---|---|
EP3349902A1 EP3349902A1 (de) | 2018-07-25 |
EP3349902B1 true EP3349902B1 (de) | 2021-05-26 |
Family
ID=57068205
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
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EP16775921.6A Active EP3349902B1 (de) | 2015-09-15 | 2016-09-15 | System zur biologischen analyse |
Country Status (4)
Country | Link |
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EP (1) | EP3349902B1 (de) |
JP (1) | JP6903638B2 (de) |
CN (1) | CN108348915B (de) |
WO (1) | WO2017048987A1 (de) |
Families Citing this family (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US11583862B2 (en) | 2015-09-15 | 2023-02-21 | Life Technologies Corporation | Systems and methods for biological analysis |
DE102018124412A1 (de) | 2018-10-02 | 2020-04-02 | Biometra GmbH | Temperierblockmodul und Vorrichtung zur thermischen Behandlung von Proben |
EP3636343A1 (de) * | 2018-10-13 | 2020-04-15 | Life Technologies Corporation | Biologisches analysesystem und -verfahren |
DE102019124588A1 (de) * | 2019-09-12 | 2021-03-18 | Biometra GmbH | Temperiervorrichtung |
Citations (2)
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US20060065652A1 (en) * | 1999-07-30 | 2006-03-30 | Stratagene California | Method for thermally cycling samples of biological material with substantial temperature uniformity |
US20110151519A1 (en) * | 2009-12-23 | 2011-06-23 | Eppendorf Ag | Laboratory Apparatus with an Arrangement for the Tempering of Samples and Method of Tempering Samples |
Family Cites Families (13)
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US7133726B1 (en) * | 1997-03-28 | 2006-11-07 | Applera Corporation | Thermal cycler for PCR |
ATE251496T1 (de) * | 1997-03-28 | 2003-10-15 | Pe Corp Ny | Einrichtung für thermozyklier-geräten für pcr |
US6123775A (en) * | 1999-06-30 | 2000-09-26 | Lam Research Corporation | Reaction chamber component having improved temperature uniformity |
US7169355B1 (en) * | 2000-02-02 | 2007-01-30 | Applera Corporation | Apparatus and method for ejecting sample well trays |
US8676383B2 (en) * | 2002-12-23 | 2014-03-18 | Applied Biosystems, Llc | Device for carrying out chemical or biological reactions |
CN1800411A (zh) * | 2005-01-04 | 2006-07-12 | 中国科学院光电技术研究所 | 热循环控制聚合酶链式反应生物检测系统 |
CA2611955A1 (en) * | 2005-06-16 | 2006-12-28 | Stratagene California | Heat blocks and heating |
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2016
- 2016-09-15 JP JP2018513585A patent/JP6903638B2/ja active Active
- 2016-09-15 CN CN201680059579.6A patent/CN108348915B/zh active Active
- 2016-09-15 EP EP16775921.6A patent/EP3349902B1/de active Active
- 2016-09-15 WO PCT/US2016/051983 patent/WO2017048987A1/en active Application Filing
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Also Published As
Publication number | Publication date |
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CN108348915A (zh) | 2018-07-31 |
CN108348915B (zh) | 2022-11-08 |
JP2018533913A (ja) | 2018-11-22 |
EP3349902A1 (de) | 2018-07-25 |
WO2017048987A1 (en) | 2017-03-23 |
JP6903638B2 (ja) | 2021-07-14 |
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