EP3349902A1 - Systems and methods for biological analysis - Google Patents
Systems and methods for biological analysisInfo
- Publication number
- EP3349902A1 EP3349902A1 EP16775921.6A EP16775921A EP3349902A1 EP 3349902 A1 EP3349902 A1 EP 3349902A1 EP 16775921 A EP16775921 A EP 16775921A EP 3349902 A1 EP3349902 A1 EP 3349902A1
- Authority
- EP
- European Patent Office
- Prior art keywords
- heating
- cooling element
- sample
- thermal
- block assembly
- Prior art date
- Legal status (The legal status 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 status listed.)
- Granted
Links
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- 238000010438 heat treatment Methods 0.000 claims abstract description 44
- 230000007246 mechanism Effects 0.000 claims description 22
- 239000004020 conductor Substances 0.000 claims description 11
- 230000002093 peripheral effect Effects 0.000 claims description 5
- 230000008878 coupling Effects 0.000 claims 1
- 238000010168 coupling process Methods 0.000 claims 1
- 238000005859 coupling reaction Methods 0.000 claims 1
- 239000000523 sample Substances 0.000 description 110
- 230000008569 process Effects 0.000 description 7
- 230000008859 change Effects 0.000 description 6
- 238000006243 chemical reaction Methods 0.000 description 5
- 230000001934 delay Effects 0.000 description 4
- 230000003287 optical effect Effects 0.000 description 4
- 101150006573 PAN1 gene Proteins 0.000 description 3
- 239000011888 foil Substances 0.000 description 3
- 239000012782 phase change material Substances 0.000 description 3
- 238000012360 testing method Methods 0.000 description 3
- 108091028043 Nucleic acid sequence Proteins 0.000 description 2
- XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 description 2
- 229910052782 aluminium Inorganic materials 0.000 description 2
- 238000013461 design Methods 0.000 description 2
- 230000007613 environmental effect Effects 0.000 description 2
- 238000007373 indentation Methods 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- 150000007523 nucleic acids Chemical group 0.000 description 2
- 238000007789 sealing Methods 0.000 description 2
- 238000000926 separation method Methods 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- 239000000758 substrate Substances 0.000 description 2
- 238000012546 transfer Methods 0.000 description 2
- 230000007704 transition Effects 0.000 description 2
- 108020004414 DNA Proteins 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- 239000006096 absorbing agent Substances 0.000 description 1
- 230000003321 amplification Effects 0.000 description 1
- 238000003491 array Methods 0.000 description 1
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- 239000011324 bead Substances 0.000 description 1
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- 238000009833 condensation Methods 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
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- 238000012986 modification Methods 0.000 description 1
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- 238000003199 nucleic acid amplification method Methods 0.000 description 1
- 239000002773 nucleotide Substances 0.000 description 1
- 125000003729 nucleotide group Chemical group 0.000 description 1
- 229920003223 poly(pyromellitimide-1,4-diphenyl ether) Polymers 0.000 description 1
- 238000012552 review Methods 0.000 description 1
- 230000035939 shock Effects 0.000 description 1
- 238000005382 thermal cycling Methods 0.000 description 1
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.
- a thermal block assembly for use in a biological analysis system includes a sample block configured to accommodate a sample holder, the sample holder configured to receive a plurality of samples, a heating and cooling element, and a heat sink including a surface.
- the surface includes a plurality of projections for engaging the heating and cooling element to hold the heating and cooling element on the heat sink.
- 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 drip pan is for engaging the sample block to seal the heating and cooling element and the heat sink from the plurality of samples in the sample holder when the sample holder is positioned on the sample block.
- the drip pan includes an ejection mechanism for ejecting the sample holder from the sample block.
- FIG. 1 is a perspective view of a biological analysis system according to one embodiment.
- FIGS. 2 and 3 are perspective views of a portion of the biological analysis system of FIG. 1 .
- FIG. 4 is an exploded view of the portion of the biological analysis system of FIG. 2.
- FIG. 5 is a perspective view of thermal block assembly of the biological analysis system of FIG. 1 .
- FIG. 6 is an exploded view of a portion of thermal block assembly of FIG. 5 with the sample block removed.
- FIG. 7 is a perspective view of the sample block of thermal block assembly of FIG. 5.
- FIG. 8 is a perspective view of the underside of the sample block of FIG. 7 and associated components.
- FIG. 9 is an exploded view of the underside of the sample block and associated components of FIG. 8.
- FIG. 10 is a perspective view of the drip pan and ejection mechanism of the biological analysis system of FIG. 1 .
- FIG. 1 1 is an enlarged view of the ejection mechanism of FIG. 10.
- FIG. 12A is a cross-sectional view of the ejection mechanism taken along the line 12A— 12A of FIG. 1 1 where the cap is in the depressed state.
- FIG. 12B is a cross-sectional view of the ejection mechanism taken along the line 12B— 12B of FIG. 1 1 where the cap is in the depressed state.
- FIG. 13A is a cross-sectional view of the ejection mechanism taken along the line 12A— 12A of FIG. 1 1 where the cap is in the expanded state.
- FIG. 13B is a cross-sectional view of the ejection mechanism taken along the line 12B— 12B of FIG. 1 1 where the cap is in the expanded state.
- FIG. 14 is an exploded view of an ejection mechanism according to one embodiment.
- FIG. 15A is a cross-sectional view of the ejection mechanism of FIG. 14 where the ejection mechanism is in the engaged state.
- FIG. 15B is a cross-sectional view of the ejection mechanism of FIG. 14 where the ejection mechanism is in the unengaged state.
- Thermal cycler system 1 0 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 1 2 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 1 8 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 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 1 8 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 1 6 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.
- 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.
- 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 1 2B), forms a seal between the sample block 20 and the drip pan 1 2 to isolate thermoelectric devices 32 from environmental conditions above the sample block 20 and the drip pan 1 2 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.
- 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.
- 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.
Abstract
Description
Claims
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 |
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EP3349902A1 true EP3349902A1 (en) | 2018-07-25 |
EP3349902B1 EP3349902B1 (en) | 2021-05-26 |
Family
ID=57068205
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
EP16775921.6A Active EP3349902B1 (en) | 2015-09-15 | 2016-09-15 | System for biological analysis |
Country Status (4)
Country | Link |
---|---|
EP (1) | EP3349902B1 (en) |
JP (1) | JP6903638B2 (en) |
CN (1) | CN108348915B (en) |
WO (1) | WO2017048987A1 (en) |
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 (en) | 2018-10-02 | 2020-04-02 | Biometra GmbH | Temperature control block module and device for the thermal treatment of samples |
EP3636343A1 (en) * | 2018-10-13 | 2020-04-15 | Life Technologies Corporation | A biological analysis system and method |
DE102019124588A1 (en) * | 2019-09-12 | 2021-03-18 | Biometra GmbH | Temperature control device |
Family Cites Families (15)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
EP2090366B1 (en) * | 1997-03-28 | 2012-12-19 | Life Technologies Corporation | Improvements in thermal cycler for PCR |
US7133726B1 (en) * | 1997-03-28 | 2006-11-07 | Applera Corporation | Thermal cycler for PCR |
US6123775A (en) * | 1999-06-30 | 2000-09-26 | Lam Research Corporation | Reaction chamber component having improved temperature uniformity |
US6657169B2 (en) * | 1999-07-30 | 2003-12-02 | Stratagene | Apparatus for thermally cycling samples of biological material with substantial 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 (en) * | 2005-01-04 | 2006-07-12 | 中国科学院光电技术研究所 | Heating cycle controlled polymerase chain reaction biological detection system |
WO2006138586A2 (en) * | 2005-06-16 | 2006-12-28 | Stratagene California | Heat blocks and heating |
CN101336061A (en) * | 2007-06-29 | 2008-12-31 | 富准精密工业(深圳)有限公司 | Radiating device |
US20100124766A1 (en) * | 2008-11-14 | 2010-05-20 | Life Technologies Corporation | Apparatus and Method for Segmented Thermal Cycler |
WO2010088405A1 (en) * | 2009-01-28 | 2010-08-05 | Amerigon Incorporated | Convective heater |
EP2338599B1 (en) * | 2009-12-23 | 2013-11-20 | Eppendorf Ag | Laboratory apparatus with an arrangement for the tempering of samples and method of tempering samples |
US20130137144A1 (en) * | 2011-06-08 | 2013-05-30 | Bio-Rad Laboratories, Inc. LSG - GXD Division | Thermal block with built-in thermoelectric elements |
US20160214110A1 (en) * | 2013-09-16 | 2016-07-28 | Life Technologies Corporation | Apparatuses, Systems and Methods for Providing Thermocycler Thermal Uniformity |
KR20160123356A (en) * | 2014-02-18 | 2016-10-25 | 라이프 테크놀로지스 코포레이션 | Apparatuses, systems and methods for providing scalable thermal cyclers and isolating thermoelectric devices |
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2016
- 2016-09-15 EP EP16775921.6A patent/EP3349902B1/en active Active
- 2016-09-15 CN CN201680059579.6A patent/CN108348915B/en active Active
- 2016-09-15 WO PCT/US2016/051983 patent/WO2017048987A1/en active Application Filing
- 2016-09-15 JP JP2018513585A patent/JP6903638B2/en active Active
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WO2017048987A1 (en) | 2017-03-23 |
EP3349902B1 (en) | 2021-05-26 |
CN108348915A (en) | 2018-07-31 |
JP6903638B2 (en) | 2021-07-14 |
CN108348915B (en) | 2022-11-08 |
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