EP0488769A2
Expired / Lapsed
EP
⏱️ 0.0 years remaining
Thermal cycler for automatic performance of the polymerase chain reaction with close temperature control
Assignee: Applied Biosystems Inc
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Filing: 1991-11-29
•
Granted: —
•
Expires: 2011-11-29
Abstract
Abstract An instrument for performing highly accurate PCR employing a sample block in microtiter tray format. The sample block has local balance and local symmetry. A three zone film heater controlled by a computer and ramp cooling solenoid valves also controlled by the computer for gating coolant flow through the block controls the block temperature. Constant bias cooling is used for small changes. Sample temperature is calculated instead of measured. A heated cover deforms plastic caps to apply a minimum acceptable threshold force for seating the tubes and thermally isolates them. The control software includes diagnostics. An install program tests and characterizes the instrument. A new user interface is used. Disposable, multipiece plastic microtiter trays to give individual freedom to sample tubes are taught.
Inventors
- 👤 Albert Carmelo Mossa
- 👤 Lisa May Goven
- 👤 John Girdner Atwood
- 👤 Fenton Williams
- 👤 Timothy M Woudenberg
- 👤 Marcel Margulies
- 👤 Robert P Ragusa
- 👤 Richard Leath
Bibliographic Details
Application Number
—
Jurisdiction
EP
Data Source
google_patents
Last Synchronized
2026-11-02 13:55
CPC Classifications
G; G05; G05D; G05D23/00; G05D23/19; G05D23/1927; G05D23/193; G05D23/1935; B; B01; B01L; B01L3/00; B01L3/50; B01L3/508; B01L3/5085; B01L3/50851; B01L3/50853; B01L7/00; B01L7/52; G05D23/1917; B01L2200/00; B01L2200/14; B01L2200/143; B01L2200/147; B01L2300/00; B01L2300/04; B01L2300/041; B01L2300/042; B01L2300/046; B01L2300/08; B01L2300/0809; B01L2300/0829; B01L2300/18; B01L2300/1805; B01L2300/1822; B01L2300/1827; B01L2300/1838; B01L2300/185; B01L3/5082
Claims Analysis
Total Claims: 182
Claim 1
Independent Claim
121 words
A system for controlling an apparatus for automated performance of polymerase chain reactions in at least one sample tube containing a known volume of a liquid sample mixture, comprising: a. a sample block having at least one well for said at least one sample tube, b. a computing apparatus, c. Heating and cooling means controlled by said computing apparatus for changing the temperature of said sample block, and d. a block temperature sensor thermally coupled to said sample block, said sensor providing to said computing apparatus the temperature of said sample block over time, wherein said computing apparatus includes means for determining the temperature of said liquid sample mixture as a function of the temperature of said sample block over time.
Claim 2
Independent Claim
121 words
A system for controlling an apparatus for automated performance of polymerase chain reactions in at least one sample tube containing a known volume of a liquid sample mixture, comprising: a. a sample block having at least one well for said at least one sample tube, b. a computing apparatus, c. Heating and cooling means controlled by said computing apparatus for changing the temperature of said sample block, and d. a block temperature sensor thermally coupled to said sample block, said sensor providing to said computing apparatus the temperature of said sample block over time, wherein said computing apparatus includes means for determining the temperature of said liquid sample mixture as a function of the temperature of said sample block over time.
Claim 3
Dependent Claim
50 words
The apparatus of claim 1, wherein said computing apparatus comprises means for storing one or more values related to a first thermal time constant corresponding to said sample tubes and said volume of said sample mixture, and storage for a second thermal time constant corresponding to said block temperature sensor.
Claim 4
Dependent Claim
43 words
The apparatus of claim 2, wherein said means for determining the sample temperature as a function of the temperature of said sample block over time includes means for determining the sample temperature as a function of said first and second thermal time constants.
Claim 5
Dependent Claim
89 words
The apparatus of claim 3, wherein said computing apparatus determines said sample temperature in a current sample interval at a current time n as: where T sam p, is equal to the sample temperature at time n, Tsampo-1 is equal to the sample temperature at an immediately preceding sample interval having occurred at time n-1, T Bn is equal to the block temperature at time n, tinterval is a time in seconds between sample intervals, and tau is said first thermal time constant minus said second thermal time constant.
Claim 6
Dependent Claim
19 words
The apparatus of claim 4, wherein said first thermal time constant is between approximately 5 seconds and 14 seconds.
Claim 7
Dependent Claim
45 words
The apparatus of claim 5 further including an input device for receiving user defined setpoints defining a hold time/temperature profile, wherein maid computing apparatus includes means for controlling said heating and cooling means as a function of said user defined setpoints and said sample temperature.
Claim 8
Dependent Claim
13 words
The apparatus of claim 6, wherein said setpoint temperatures are target sample temperatures.
Claim 9
Dependent Claim
45 words
The apparatus of claim 1 further including an input device for receiving user defined setpoints defining a hold time/temperature profile, wherein said computing apparatus includes means for controlling maid heating and cooling means as a function of maid user defined setpoints and said sample temperature.
Claim 10
Dependent Claim
76 words
The apparatus of claim 7, wherein said sample block is comprised of a central region containing in an upper surface an array of sample wells for holding said sample tubes, an end edge region comprising two end edges at opposite ends of said block which are in thermal contact with ambient, and a manifold region comprising two manifold edges at opposite sides of said block, wherein each said manifold edge is thermally coupled to a manifold.
Claim 11
Dependent Claim
45 words
The apparatus of claim 9 wherein said heating means is a heater having a central heating zone thermally coupled to said central region, an end edge heating zone thermally coupled to said edge region, and a manifold heating zone thermally coupled to maid manifold region.
Claim 12
Dependent Claim
115 words
The apparatus of claim 10 wherein said computing apparatus determines a first power to be applied to said heating zones in said current sample interval by: a. determining a theoretical second power representing the total power to apply to said block in said current sample interval without accounting for power losses, b. dividing said theoretical second power into theoretical powers to be applied to each said individual zone in said current sample interval, c. determining power losses by said regions in said current sample interval, and d. determining an actual third power to be applied to each said individual zone in said current sample interval, said third power accounting for power losses by said regions.
Claim 13
Dependent Claim
154 words
The apparatus of claim 11, wherein one of said user defined setpoints is the target sample temperature after ramping said sample temperature at said preselected ramp rate, and wherein said computing apparatus includes means for determining said theoretical second power to be applied to all said zones, including: a. means for determining a total fourth power to all heating zones to achieve said preselected ramp rate, b. means for determining said temperature of the sample block in said current sample interval as a function of said fourth power, c. means for determining said sample temperature in said current sample internal, d. means for determining a fraction of the difference between the target sample temperature after ramping and the sample temperature in said immediately preceding sample interval to be made up in said current sample internal, and e. means for determining said theoretical second power to make up said friction in said current sample interval.
Claim 14
Dependent Claim
104 words
The apparatus of claim 12 additionally comprising bias cooling constantly applied to said sample block, wherein said computing apparatus includes means for determining a total fourth power to all heating zones to achieve a desired ramp rate according to: Power - CP/ramp_rate + bias where Power is said total power to all heating zones to achieve a desired ramp rate, CP equals the thermal mass of said block, bias is the cooling power of said bias cooling and ramp_rate is the difference between the target sample temperature after ramping and the sample temperature at the commencement of ramping divided by a preselected ramp rate.
Claim 15
Dependent Claim
64 words
The apparatus of claim 12 or 13, wherein said computing apparatus determines said temperature of said sample block in said current sample interval according to: where T Bn-1 is equal to the temperature of the block at time n-1, tinterval is the time in seconds between sample intervals, CP is equal to a thermal mass of said block, and power is said fourth power.
Claim 16
Dependent Claim
97 words
The apparatus of claim 12,13 or 14 wherein said computing apparatus determines said theoretical second power to make up said friction in said current sample interval as a function of where P w , equals said theoretical second power to be applied to make up said fraction in said current sample interval, CP is equal to a thermal mass of said block, SP equals said target sample temperature after ramping, and F is said fraction of the difference between said target temperature after ramping and said sample temperature to be made up in said current sample interval.
Claim 17
Dependent Claim
13 words
The apparatus of claim 14 or 15 wherein t interval equals approximately 0.2.
Claim 18
Dependent Claim
21 words
The apparatus of claim 1, wherein said known volume of liquid sample mixture is in the range of approximately 20-100 microliters.
Claim 19
Independent Claim
57 words
The apparatus of any of claims 12 through 15, wherein said computing apparatus adjusts said theoretical second power to make up said fraction in said current sample interval when said sample temperature in said immediately preceding sample interval is within an integral band of said target sample temperature after ramping, in order to close out remaining error.
Claim 20
Dependent Claim
15 words
The apparatus of claim 18, wherein said integral band is approximately + /- 0.5° C.
Claim 21
Independent Claim
115 words
The apparatus of any of claims 12-19, wherein said computing apparatus adjusts said theoretical second power to make up said fraction in said current sample interval by adding thereto a power adjustment term, to account for power which, because of physical limitations, was not delivered in previous sample intervals, given by: where pwr_adj equals said power adjustment term, int_sum n is a value of an accumulating integral term at time n, int_sum n - i is a value of said accumulating integral term at time n-1, SP equals said target sample temperature after ramping, T sampn-1 equals the temperature of the sample at time n - 1 , and ki equals an integral gain constant.
Claim 22
Dependent Claim
13 words
The apparatus of claim 20, wherein said integral gain constant is approximately 512.
Claim 23
Dependent Claim
35 words
The apparatus of claim 11, wherein said computing apparatus divides said theoretical second power into the theoretical power to be applied to each said individual zone in proportion to the relative areas of said zones.
Claim 24
Dependent Claim
59 words
The apparatus of claim 11, wherein said computing apparatus determines power losses by: a. determining power lost to a foam backing on said sample block in said current sample interval b. determining power lost to said manifolds in said current sample interval, and c. determining power lost in said end edge region to ambient in said current sample interval.
Claim 25
Dependent Claim
89 words
The apparatus of claim 23, wherein said computing apparatus determines said power lost to said foam backing in said current sample interval by: a. determining temperature of said foam backing in said current sample interval, b. determining the block temperature in said current sample interval, and c. determining said power lost to said foam backing a a function of said temperature of said foam backing in said current sample interval, said temperature of said block in said current sample interval, and a thermal time constant of said foam backing.
Claim 26
Dependent Claim
63 words
The apparatus of claim 24, wherein said computing apparatus determines the temperature of the foam backing in said current sample interval, T foam , according to: where T foam , is equal to the temperature of the foam at time n, T foamn-1 is equal to the foam temperature at time n-1, and tau2 is said thermal time constant of said foam backing.
Claim 27
Dependent Claim
17 words
The apparatus of claim 25, wherein tau2 is approximately 30 seconds and t interval is approximately 0.2.
Claim 28
Independent Claim
75 words
The apparatus of any of claims 24-26, wherein said computing apparatus determines said temperature of said sample block in said current sample intervall according to: where T Bn-1 is equal to the temperature of the block at time n-1, tinterval is the time in seconds between sample intervals, CP is equal to the thermal mass of said block, and Power is a total fourth power to all heating zones to achieve said preselected ramp rate.
Claim 29
Independent Claim
70 words
The apparatus of any of claims 24-27, wherein said computing apparatus determines the power lost to said foam backing as a function of said temperature of said foam backing according to: where foam-pwr is said power lost to said foam backing at time n, T foam , is equal to the temperature of the foam at time n and C is equal to the thermal mass of the foam backing.
Claim 30
Independent Claim
104 words
The apparatus of any of claims 23-28 additionally comprising means for delivering a bias coolant constantly applied to said sample block, wherein said computing apparatus determines the power lost to said manifolds in said current sample interval according to: where manifold_loss equals said power lost to said manifolds in said current sample interval, KA equals an end edge region-to-ambient conductance constant, T An equals the ambient temperature at the time n, Tc equals a temperature of said bias coolant at time n, KC equals a sample block-to-coolant conductance constant, Tm equals the thermal mass of said manifolds and dT/dt equals said preselected ramp rate.
Claim 31
Independent Claim
106 words
The apparatus of any of claims 23-29, wherein said apparatus for performing automated polymerase chain reactions includes an enclosure for said sample block defining an enclosed ambient atmosphere and said computing apparatus determines the power lost to ambient in said currant sample interval according to: where ambient-loss is said power lost to said ambient in said current sample interval, K2A equals an end edge region-to-ambient conductance constant, Tkequals ambient temperature at time n, K2C equals an end edge region-to-coolant constant, T Co equals the coolant temperature at time n, TM2 equals the thermal mass of said enclosed ambient atmosphere, and dT/dt equals said preselected ramp rate.
Claim 32
Dependent Claim
152 words
The apparatus of claim 11, wherein said computing apparatus determines said actual power to be applied to each said individual zone in said current sample interval according to: where pwr equals said theoretical power, manifold loss equals a power lost to said manifolds in said current sample interval, ambient loss equals a power lost in said edge region to said ambient in said current sample interval, central_pwr equals a power to be applied to said central heating zone in said current sample interval, manifold_pwr equals a power to be applied to said manifold heating zone in said current sample interval, edge_pwr equals a power to be applied to said end edge heating zone in maid current sample interval, cper equals fraction of sample block area in said central region, mper equals fraction of sample block area in said manifold region, and eper equals fraction of sample block area in said edge region.
Claim 33
Dependent Claim
19 words
The apparatus of claim 31, wherein cper equals approximately .66, mper equals approximately .20 and eper equals approximately .14.
Claim 34
Dependent Claim
67 words
The apparatus of claim 9, wherein said sample block contains multiple transverse bias cooling channels alternating with multiple transverse ramp cooling channels, said bias and ramp cooling channels being parallel to said upper surface, said apparatus further comprising means for consistently pumping chilled coolant through said bias cooling channels and value means controlled by said computing apparatus for selectively pumping chilled coolant through said ramp cooling channels.
Claim 35
Dependent Claim
20 words
The apparatus of claim 33 wherein said computing apparatus determines a theoretical cooling power to be applied to said block.
Claim 36
Dependent Claim
124 words
The apparatus of claim 34 wherein said computing apparatus includes means for determining said cooling power, including a. means for determining a total fifth power to said block to achieve a desired downward ramp rate, b. means for determining said temperature of the sample block in said current sample internal as a function of said fifth power, c. means for determining said sample temperature in said current sample interval, d. means for determining a fraction of the difference between the target sample temperature after ramping downward and the sample temperature in said immediately preceding sample interval to be made up in said current sample interval, and e. means for determining said theoretical cooling power to make up maid fraction in said current sample interval.
Claim 37
Dependent Claim
98 words
The apparatus of claim 35 additionally comprising bias cooling constantly applied to said sample block, wherein maid computing apparatus includes means for determining a total fourth power to all heating zones to achieve a desired ramp rate according to: where Power is said total power to said block to achieve a desired ramp rate, CP equals the thermal mass of said block, bias is the cooling power of said bias cooling and ramp_rate is the difference between the target sample temperature after ramping and the sample temperature at the commencement of ramping divided by a preselected ramp rate.
Claim 38
Dependent Claim
93 words
The apparatus of claim 36, wherein said computing apparatus determines said theoretical cooling power to make up said fraction in said current sample interval as a function of where Pwr equals said theoretical cooling power to be applied to make up said fraction in said current sample interval, CP is equal to a thermal mass of said block, SP equals said target sample temperature after ramping, and F is said fraction of the difference between said target temperature after ramping and said sample temperature to be made up in said current sample interval.
Claim 39
Dependent Claim
88 words
The apparatus of claim 37, wherein said computing apparatus determines a power lost to said manifolds in said current sample interval according to: where manifold_loss equals said power lost to said manifolds in said current sample interval, KA equals an end edge region-to-ambient conductance constant, T An equals the ambient temperature at the time n, Tc equals a temperature of said bias coolant at time n, KC equals a sample block-to-coolant conductance constant, Tm equals the thermal mass of said manifolds and dT/dt equals said preselected ramp rate.
Claim 40
Dependent Claim
107 words
The apparatus of claim 38, wherein said apparatus for performing automated polymerase chain reactions includes an enclosure for said sample block defining an enclosed ambient atmosphere and said computing apparatus determines a power lost to ambient in said current sample interval according to: where ambient loss is said power lost to said ambient in said current sample interval, K2A equals an end edge region-to-ambient conductance conatant, T An equals ambient temperature at time n, K2C equals an end edge region-to-coolant constant, T Co equals the coolant temperature at time n, TM2 equals the thermal mass of said enclosed ambient atmosphere, and dT/dt equals said preselected ramp rate.
Claim 41
Dependent Claim
106 words
The apparatus of claim 39 wherein said computing apparatus includes valve means for opening said channels for cooling said block at said current sample interval, comprising means for: a. means for determining that ramp direction is downward, b. means for determining an intermediate power value by subtracting values for power lost to said manifolds end said ambient from said theoretical cooling power, c. means for determining a cooling breakpoint as a function of said block temperature and a temperature of said coolant, and d. means for determining if said ramp cooling channels shall be opened as a function of said intermediate power and maid cooling breakpoint.
Claim 42
Dependent Claim
36 words
The apparatus of claim 40, wherein said cooling breakpoint is a function of the difference between said block temperature at said current sample interval and said temperature of said coolant fluid at said current sample interval.
Claim 43
Dependent Claim
23 words
The apparatus of claim 41, wherein said ramp cooling channels will be open if said intermediate power is less than said cooling breakpoint.
Claim 44
Dependent Claim
30 words
The apparatus of claim 7, wherein the controlling of said heating and cooling means as a function of said user defined setpoints constitutes running said profile as a profile run.
Claim 45
Dependent Claim
19 words
The apparatus of claim 43, wherein said computing apparatus comprises means for allowing users to invoke said profile runs.
Claim 46
Dependent Claim
40 words
The apparatus of claim 44, wherein said input device further comprises means for receiving a user defined cycle count for each said profile, said cycle count constituting the number of times said profile will be run when it is invoked.
Claim 47
Dependent Claim
51 words
The apparatus of claim 45, wherein said computing apparatus further comprises means for linking multiple profiles in any order to form a protocol, said protocol defining a sequence of said profiles to be run, wherein invoking said sequence of profiles to be run constitutes running said protocol as a protocol run.
Claim 48
Dependent Claim
25 words
The apparatus of claim 46, wherein said computing apparatus further comprises means for linking a single profile a plurality of times in a single protocol.
Claim 49
Independent Claim
20 words
The apparatus of either of claims 46-47, wherein said computing apparatus further comprises means for storing a plurality of protocols.
Claim 50
Independent Claim
24 words
The apparatus of any of claims 46-48, wherein said computing apparatus comprises means for including any said profile in a plurality of said protocols.
Claim 51
Independent Claim
26 words
The apparatus of any of claims 46-49, wherein said computing apparatus comprises means for protecting a profile included in any protocol from being deleted or overwritten.
Claim 52
Dependent Claim
28 words
The apparatus of claim 43, further comprising a means to determine that electrical power to operate said apparatus went off during a said run of a said profile.
Claim 53
Dependent Claim
24 words
The apparatus of claim 51 further comprising a means to report the length of said electrical power outage when said electrical power is restored.
Claim 54
Independent Claim
36 words
The apparatus of either of claims 51-52, further comprising means for automatically starting a soak upon restoration of said electrical power, said soak being at a temperature selected to maximize the chance of saving said samples.
Claim 55
Dependent Claim
14 words
The apparatus of claim 53, wherein said temperature to save said samples is 4°C.
Claim 56
Independent Claim
29 words
The apparatus of any of claims 45-54 further including means for automatically increasing the hold time of any or all setpoints from cycle to cycle in said cycle count.
Claim 57
Dependent Claim
36 words
The apparatus of claim 55, wherein activation of said means for automatically increasing the hold time of any or all setpoints from cycle to cycle is selectable as a user level option via said input device.
Claim 58
Independent Claim
35 words
The apparatus of either of claims 55-56, wherein said automatic increases in the hold time of any or all setpoints from cycle to cycle are by first user defined values input via said input device.
Claim 59
Dependent Claim
26 words
The apparatus of claim 57, wherein said automatic increases in the hold time from cycle to cycle are linear based on said first user defined values.
Claim 60
Dependent Claim
26 words
The apparatus of claim 57, wherein said automatic increases in the hold time from cycle to cycle are geometric based on said first user defined values.
Claim 61
Independent Claim
29 words
The apparatus of any of claims 45-59 further including means for automatically decreasing the hold time of any or all setpoints from cycle to cycle in said cycle count.
Claim 62
Dependent Claim
36 words
The apparatus of claim 60, wherein activation of said means for automatically decreasing the hold time of any or all setpoints from cycle to cycle is selectable as a user level option via said input device.
Claim 63
Independent Claim
35 words
The apparatus of either of claims 60-61, wherein said automatic decreases in the hold time of any or all setpoints from cycle to cycle are by second user defined values input via said input device.
Claim 64
Dependent Claim
26 words
The apparatus of claim 62, wherein said automatic decreases in the hold time from cycle to cycle are linear based on said second user defined values.
Claim 65
Dependent Claim
26 words
The apparatus of claim 62, wherein said automatic decreases in the hold time from cycle to cycle are geometric based on said second user defined values.
Claim 66
Independent Claim
29 words
The apparatus of any of claims 45-64 further including means for automatically increasing the setpoint temperature of any or all setpoints from cycle to cycle in said cycle count.
Claim 67
Dependent Claim
36 words
The apparatus of claim 65, wherein activation of said means for automatically increasing the setpoint temperature of any or all setpoints from cycle to cycle is selectable as a user level option via said input device.
Claim 68
Independent Claim
35 words
The apparatus of either of claims 65-66, wherein said automatic increases in the setpoint temperature of any or all setpoints from cycle to cycle are by third user defined values input via said input device.
Claim 69
Dependent Claim
26 words
The apparatus of claim 67, wherein said automatic increases in the setpoint temperature from cycle to cycle are linear based on said third user defined values.
Claim 70
Dependent Claim
26 words
The apparatus of claim 67, wherein said automatic increases in the setpoint temperature from cycle to cycle are geometric based on said third user defined values.
Claim 71
Independent Claim
29 words
The apparatus of any of claims 45-69 further including means for automatically decreasing the setpoint temperature of any or all setpoints from cycle to cycle in said cycle count.
Claim 72
Dependent Claim
36 words
The apparatus of claim 70, wherein activation of said means for automatically decreasing the setpoint temperature of any or all setpoints from cycle to cycle is selectable as a user level option via said input device.
Claim 73
Independent Claim
35 words
The apparatus of either of claims 70-71, wherein said automatic decreases in the setpoint temperature of any or all setpoints from cycle to cycle are by fourth user defined values input via said input device.
Claim 74
Dependent Claim
26 words
The apparatus of claim 72, wherein said automatic decreases in the setpoint temperature from cycle to cycle are linear based on said fourth user defined values.
Claim 75
Dependent Claim
25 words
The apparatus of claim 72, wherein said automatic decreases in the temperature from cycle to cycle are geometric based on said fourth user defined values.
Claim 76
Independent Claim
26 words
The apparatus of any of claims 43-74, further comprising a programmed pause option means to automatically halt a run for a user defined period of time.
Claim 77
Dependent Claim
41 words
The apparatus of claim 75, wherein said pause option means comprises means to halt said run after any or all setpoints are complete, during any or all cycles and after any or all of the profiles in a protocol are run.
Claim 78
Independent Claim
45 words
The apparatus of any of claims 7-76 further comprising a means to allow a user to define, via said input device, a temperature range such that said setpoint hold time will begin when said sample temperature is within said temperature range of said setpoint temperature.
Claim 79
Dependent Claim
44 words
The apparatus of claim 2, further comprising an input device for receiving a tube type and a reaction volume, and wherein said computing apparatus determines said thermal time constant for said reaction tube as a function of said tube type and said reaction volume.
Claim 80
Dependent Claim
17 words
The apparatus of claim 10, further comprising a means for performing diagnostic checks of said heating means.
Claim 81
Dependent Claim
26 words
The apparatus of claim 79, wherein said checks comprise one or more heater ping tests, block thermal capacity tests, ramp cooling conductance tests, sensor lag tests.
Claim 82
Dependent Claim
17 words
The apparatus of claim 33, further comprising a means for performing diagnostic checks of said cooling means.
Claim 83
Dependent Claim
32 words
The apparatus of claim 81, wherein said checks comprise one or more control cooling conductance tests, block thermal capacity tests, chiller tests, ramp cooling conductance tests, sensor lag tests, coolant capacity tests.
Claim 84
Dependent Claim
21 words
The apparatus of claim 1, further comprising a means for performing hardware diagnostics on user demand and/or automatically upon system start-up.
Claim 85
Dependent Claim
97 words
The apparatus of claim 55, wherein said hardware diagnostics include tests of one or more of a Programmable Peripheral interface device, Battery RAM device, Battery RAM checksum, EPROM devices, Programmable Interface Timer devices, Clock/Calendar device, Programmable Interrupt Controller device, Analog to Digital Section, RS-232 Section, Display Section, Keyboard, Beeper, Ramp Cooling Values, EPROM mismatch, Firmware version level, Battery RAM Checksum and Initialization, Autostart Program Flag, Clear Calibration Flag, Heated Cover heater and control circuitry, Edge heater and control circuitry, Manifold heater and control circuitry, Central heater and control circuitry, Sample block thermal cutoff, Heated cover thermal cutoff.
Claim 86
Dependent Claim
20 words
The apparatus of claim 43 further including means for adjusting temperature sensor readings to account for drift in analog circuitry.
Claim 87
Dependent Claim
49 words
The apparatus of claim 85 wherein said means for adjusting temperature sensor readings to account for drift in the analog circuitry determines said drift by a) Measuring one or more test voltages under controlled conditions, b) Reading said voltages at the start of each run to measure electronic drift.
Claim 88
Dependent Claim
42 words
The apparatus of claim 46, wherein said computing apparatus comprises a means to display, during a run, the approximate amount of time left in the run of a profile and/or all of the profiles left to be run in a running protocol.
Claim 89
Independent Claim
29 words
The apparatus of any of claims 43-50, wherein said computing apparatus comprises a means to display, during a run, the sample temperature at any given time in the run.
Claim 90
Dependent Claim
37 words
The apparatus of claim 7, further comprising means for determining, for a given setpoint, a first difference between said sample temperature at the end of said setpoint hold time and said setpoint sample temperature of said setpoint.
Claim 91
Dependent Claim
20 words
The apparatus of claim 89, wherein said input device further comprises a means for receiving a user defined temperature differential.
Claim 92
Dependent Claim
27 words
The apparatus of claim 90, wherein said computing apparatus comprises means to report an error if said user defined temperature differential is greater than said first difference.
Claim 93
Dependent Claim
21 words
The apparatus of claim 7, further comprising means to configure the temperature the apparatus will return to during any idle state.
Claim 94
Dependent Claim
23 words
The apparatus of claim 7, further comprising means to check that said setpoint sample temperature is reached within a predetermined amount of time.
Claim 95
Independent Claim
31 words
The apparatus of any of claims 65-74, further comprising a means to check that the said automatically modified setpoint sample temperature has not exceeded 100°C and/or has not gone below 0°C.
Claim 96
Independent Claim
23 words
The apparatus of any of claims 55-74, further comprising a means to check that said automatically modified setpoint hold time is not negative.
Claim 97
Dependent Claim
44 words
The apparatus of claim 1 further comprising means to continually monitor said block sensor and to invoke an abort procedure if said sensor readings are above a maximum desireable temperature for said block by a predetermined number of degrees a predetermined number of times.
Claim 98
Dependent Claim
34 words
The apparatus of claim 96, wherein said abort procedure includes one or more of aborting the running profile, flagging the error in a history file, displaying message alerts to a user, disabling said heaters.
Claim 99
Independent Claim
17 words
The apparatus of any of claims 43-50, further comprising means for printing information stored in said system.
Claim 100
Dependent Claim
34 words
The apparatus of claim 98, wherein said information includes at least one of: contents of a profile, contents of a protocol, listing of created profiles, listing of created protocols, configuration parameters, system calibration parameters.
Claim 101
Independent Claim
19 words
The apparatus of any of claims 1-99, further comprising the ability to perform all available user interface junctions remotely.
Claim 102
Independent Claim
27 words
The apparatus of any of claims 1-99 wherein said computing apparatus comprises means to display a menu driven user interface to reduce user reliance on written manuals.
Claim 103
Independent Claim
33 words
The apparatus of any of claims 43-50 wherein said computing apparatus maintains a history file of an immediately previous run containing details of said previous run intended for integrity checks and error analysis.
Claim 104
Independent Claim
132 words
A method for computer control of the automated performance of polymerase chain reactions in at least one sample tube containing a known volume of liquid sample mixture by means of a computer-controlled thermocycler including a computing apparatus, a sample block having at least one well for said at least one sample tube, a block temperature sensor thermally coupled to said sample block, and heating and cooling means controlled by said computing apparatus for changing the temperature of said sample block, comprising the steps by said computing apparatus of a. reading the block temperature at predetermined times, b. determining the temperature of said liquid sample mixture as a function of the temperature of said sample block over time, and c. controlling said heating and cooling means as a function of said sample temperature.
Claim 105
Independent Claim
132 words
A method for computer control of the automated performance of polymerase chain reactions in at least one sample tube containing a known volume of liquid sample mixture by means of a computer-controlled thermocycler including a computing apparatus, a sample block having at least one well for said at least one sample tube, a block temperature sensor thermally coupled to said sample block, and heating and cooling means controlled by said computing apparatus for changing the temperature of said sample block, comprising the steps by said computing apparatus of a. reading the block temperature at predetermined times, b. determining the temperature of said liquid sample mixture as a function of the temperature of said sample block over time, and c. controlling said heating and cooling means as a function of said sample temperature.
Claim 106
Dependent Claim
139 words
The method according to claim 103 wherein said step of determining the temperature of said liquid sample comprises the steps of (i) determining a first thermal time constant for said at least one sample tube and said volume of liquid sample mixture, (ii) determining a second thermal time constant for said block temperature sensor, and (iii.) determining the sample temperature in a current sample interval at a current time n according to the formula where T sam p, is equal to the sample temperature at time n, Tsampo-1 is equal to the sample temperature at an immediately preceding sample interval having occurred at time n-1, T Bn is equal to the block temperature at time n, tinterval is a time in seconds between sample intervals, and tau is said first thermal time constant minus said second thermal time constant.
Claim 107
Dependent Claim
152 words
The method according to claim 103 wherein said sample block comprises a central region containing said at least one well, an end edge region in thermal contact with ambient and a manifold region thermally coupled to at least one manifold, wherein said heating means includes a zone for each of said regions, and wherein the step of controlling said heating means comprises the step of (iv) determining a theoretical second power representing the total power to apply to said block in a current sample interval at a current time n without accounting for power losses, (v) dividing said theoretical second power into theoretical powers, one to be applied to each of said heating zones, (vi) determining power losses by said regions in said current sample interval, and (vii) determining an actual third power for each of said zones in said current sample interval to account for power loss by each said zone.
Claim 108
Dependent Claim
175 words
The method according to claim 105 wherein said thermocycler additionally includes bias cooling constantly applied to said sample block, wherein said computer-controlled cooling means comprises selectively operable ramp cooling means for selectively delivering a cooling fluid to said sample block, and wherein the step of controlling said selectively operable ramp cooling means includes the steps of (viii) determining that sample temperature ramp direction is downward, (ix) determining the temperature of said cooling fluid, (x) determining as a function of said sample temperature a total cooling power to apply to said block in said current sample interval without accounting for power losses, (xi) determining an intermediate cooling power by subtracting power loss to said at least one manifold and to ambient from said total cooling power, (xii) determining a cooling breakpoint as a function of the difference between the block temperature and the temperature of said cooling fluid in the current sample interval, and (xiii) selectively operating said ramp cooling means as a function of the difference between said intermediate cooling power and said cooling breakpoint.
Claim 109
Dependent Claim
147 words
Thermocycler apparatus suitable for automated performance of the polymerase chain reaction comprising a. a metal sample block having a major top surface and a major bottom surface, b. an array of spaced-apart sample wells formed in said major top surface, c. bias cooling constantly applied to said sample block at a rate sufficient to cause said block, if at a temperature within the range of 35-100°C, to cool uniformly at a rate of at least about 0.1 °C/sec unless external heat is supplied, and d. computer-controllable heating means responsive to said compuer system capable of uniformly raising the temperature of said block at a rate greater than the bias cooling rate, said thermocycler apparatus being capable, under the control of a computer, of maintaining the array of sample wells at a constant in the range of 35-100°C within a tolerance band of plus or minus about 0.5°C.
Claim 110
Dependent Claim
147 words
Thermocycler apparatus suitable for automated performance of the polymerase chain reaction comprising a. a metal sample block having a major top surface and a major bottom surface, b. an array of spaced-apart sample wells formed in said major top surface, c. bias cooling constantly applied to said sample block at a rate sufficient to cause said block, if at a temperature within the range of 35-100°C, to cool uniformly at a rate of at least about 0.1 °C/sec unless external heat is supplied, and d. computer-controllable heating means responsive to said compuer system capable of uniformly raising the temperature of said block at a rate greater than the bias cooling rate, said thermocycler apparatus being capable, under the control of a computer, of maintaining the array of sample wells at a constant in the range of 35-100°C within a tolerance band of plus or minus about 0.5°C.
Claim 111
Dependent Claim
19 words
Thermocycler apparatus according to claim 107 wherein said array comprises a rectangular array having roughly of spaced-apart sample wells.
Claim 112
Dependent Claim
26 words
Thermocycler apparatus according to claim 108 wherein said array comprises an 8-by-12 rectangular array having center-to-center sample well spacing compatible with industry standard microtiter plate format.
Claim 113
Dependent Claim
21 words
Thermocycler apparatus according to claim 109 wherein said sample block has a block thermal capacity of about 500-600 watt-seconds per °C.
Claim 114
Dependent Claim
50 words
Thermocycler apparatus according to claim 108 wherein said sample block contains multiple transverse bias cooling channels through said block parallel to said top surface and parallel to and spaced from the rows of wells, and wherein said bias cooling is applied by pumping cooling liquid through said bias cooling channels.
Claim 115
Dependent Claim
13 words
Thermocycler apparatus according to claim 111 wherein said bias cooling channels are insulated.
Claim 116
Dependent Claim
53 words
Thermocycler apparatus according to claim 107 wherein said computer-controllable heating means comprises multiple, separately controllable heating zones for said block, at least one first zone for the portion of the block containing the array of sample wells and at least one second zone for the peripheral portion of the block outside the array.
Claim 117
Dependent Claim
24 words
Thermocycler apparatus according to claim 123 wherein said computer-controllable heating means comprises a multizone film heater in thermal contact with said major bottom surface.
Claim 118
Dependent Claim
39 words
Thermocycler apparatus according to claim 107 wherein said sample block includes around its periphery a guard band having thermal characteristics similar to the block portion containing the array and wherein said guard band is bias cooled and controllably heated.
Claim 119
Dependent Claim
38 words
Thermocycler apparatus according to claim 115 wherein said guard band includes a groove formed in said top surface extending substantially around said array, decreasing the thermal conductivity between the block portion containing the array and the guard band.
Claim 120
Dependent Claim
47 words
Thermocycler apparatus according to claim 115 wherein said computer-controllable heating means comprises multiple, separately controllable heating zones for said block, at least one first zone for the portion of the block containing the array of sample wells and at least one second zone for the guard band.
Claim 121
Dependent Claim
24 words
Thermocycler apparatus according to claim 117 wherein said computer-controllable heating means comprises a multizone film heater in thermal contact with said major bottom surface.
Claim 122
Dependent Claim
41 words
Thermocycler apparatus according to claim 107 further comprising computer-controllable ramp cooling means capable of lowering the temperature of said block at a rate of at least about 4°C per second from 100°C and at least about 2°C per second from 40°C.
Claim 123
Dependent Claim
61 words
Thermocycler apparatus according to claim 119 wherein said array comprises a rectangular array comprising rows of spaced-apart sample wells, wherein said sample block contains multiple transverse bias cooling channels alternating with multiple transverse ramp cooling channels, and wherein said bias cooling and said ramp cooling are applied by pumping cooling liquid through said ramp cooling channels and said bias cooling channels.
Claim 124
Dependent Claim
21 words
Thermocycler apparatus according to claim 120 further comprising means to deliver cooling liquid to opposite ends of successive ramp cooling channels.
Claim 125
Dependent Claim
16 words
Thermocycler apparatus according to claim 119 wherein said computer-controllable heating means is capable of ramp heating.
Claim 126
Dependent Claim
51 words
Thermocycler apparatus according to claim 122 wherein said controllable heating comprises multiple, separately controllable heating zones for said block, at least one first zone for the portion of the block containing the array of sample wells and at least one second zone for the portion of the block outside the array.
Claim 127
Dependent Claim
24 words
Thermocycler apparatus according to claim 123 wherein said computer-controllable heating means comprises a multizone film heater in thermal contact with said major bottom surface.
Claim 128
Dependent Claim
49 words
Thermocycler apparatus according to claim 107 further comprising means for seating into the wells in said array sample tubes of nonidentical height with a seating force on each sample tube sufficient to cause a snug, flush fit between the surface of the tube and the surface of the well.
Claim 129
Dependent Claim
43 words
Thermocycler apparatus according to claim 125 wherein said means for seating comprises deformable, compliant, gas-tight caps for said sample tubes, a vertically displaceable platen, and controllable means for forcibly lowering said platen to maintain said seating force on the cap for each tube.
Claim 130
Dependent Claim
20 words
Thermocycler apparatus according to claim 126 wherein said platen is maintained at a heated temperature in the range of 94-110°C.
Claim 131
Dependent Claim
19 words
Thermocycler apparatus according to claim 127 wherein said platen is maintained at a temperature in the range of 100-110°C.
Claim 132
Dependent Claim
18 words
Thermocycler apparatus according to any of claims 107-128 further comprising a computer system for controlling said heating means.
Claim 133
Dependent Claim
17 words
Thermocycler apparatus according to any of claims 119-124 wherein said computer system controls said ramp cooling means.
Claim 134
Dependent Claim
322 words
Thermocycler apparatus suitable for automated, rapid performance of the polymerase chain reaction comprising a. a thermally homogeneous metal sample block of low thermal mass having a major top surface and a major bottom surface, said block containing in a central region of its upper surface an 8-by-12 rectangular array of sample wells having center-to-center spacing compatible with industry standard microtiter plate format, said block also containing a peripheral region surrounding said array, said peripheral region comprising a guard band having thermal characteristics similar to the thermal characteristics of the central region, b. a bias cooling system for constantly cooling said sample block at a bias cooling rate sufficient to cause said block, if at a temperature within the range of35-100°C, to cool uniformly at a rate of at least about 0.1°C/sec unless external heat is supplied, c. a computer system for receiving and storing user data regarding times and temperatures defining a plurality of reaction cycles, d. a ramp cooling system controlled by said computer system for selectively cooling said sample block at a ramp cooling rate of at least about 4°C/sec from 100°C and at least about 2°C/sec from 40°C, e. a multizone heating system controlled by said computer system having a heating zone for the central region of the block and a heating zone for the guard band, said heating system being capable of providing heat necessary to maintain the sample block at a constant temperature in the range of 35-100°C and also capable of providing ramp heating to the block, f. a pressing cover vertically displaceable above said sample block, and g. cover displacing means for raising said cover and for lowering said cover and maintaining its vertical position against a resisting force of at least about 3000 grams, said thermocycler apparatus being capable of maintaining the array of sample wells at a constant temperature in the range of 35-100°C within a tolerance band of plus or minus 0.5°C.
Claim 135
Dependent Claim
322 words
Thermocycler apparatus suitable for automated, rapid performance of the polymerase chain reaction comprising a. a thermally homogeneous metal sample block of low thermal mass having a major top surface and a major bottom surface, said block containing in a central region of its upper surface an 8-by-12 rectangular array of sample wells having center-to-center spacing compatible with industry standard microtiter plate format, said block also containing a peripheral region surrounding said array, said peripheral region comprising a guard band having thermal characteristics similar to the thermal characteristics of the central region, b. a bias cooling system for constantly cooling said sample block at a bias cooling rate sufficient to cause said block, if at a temperature within the range of35-100°C, to cool uniformly at a rate of at least about 0.1°C/sec unless external heat is supplied, c. a computer system for receiving and storing user data regarding times and temperatures defining a plurality of reaction cycles, d. a ramp cooling system controlled by said computer system for selectively cooling said sample block at a ramp cooling rate of at least about 4°C/sec from 100°C and at least about 2°C/sec from 40°C, e. a multizone heating system controlled by said computer system having a heating zone for the central region of the block and a heating zone for the guard band, said heating system being capable of providing heat necessary to maintain the sample block at a constant temperature in the range of 35-100°C and also capable of providing ramp heating to the block, f. a pressing cover vertically displaceable above said sample block, and g. cover displacing means for raising said cover and for lowering said cover and maintaining its vertical position against a resisting force of at least about 3000 grams, said thermocycler apparatus being capable of maintaining the array of sample wells at a constant temperature in the range of 35-100°C within a tolerance band of plus or minus 0.5°C.
Claim 136
Dependent Claim
23 words
Thermocycler apparatus according to claim 131 wherein said pressing cover comprises a heated platen maintainable at a temperature in the range of 94-110°C.
Claim 137
Dependent Claim
26 words
Thermocycler apparatus according to claim 131 wherein said multizone heating system comprises a film heater in thermal contact with the bottom surface of the sample block.
Claim 138
Dependent Claim
48 words
Thermocycler apparatus according to claim 133 wherein said bias cooling system comprises a series of bias cooling channels through said block parallel to said top surface and parallel to and spaced from the rows of wells, and pump means for pumping cooling liquid through said bias cooling channels.
Claim 139
Dependent Claim
58 words
Thermocycler apparatus according to claim 134 wherein said ramp cooling system comprises a series of ramp cooling channels through said block parallel to the bias cooling channels and spaced apart therefrom and from the rows of wells, and pump means for pumping cooling liquid through said ramp cooling channels, entering at opposite ends of successive ramp cooling channels.
Claim 140
Dependent Claim
24 words
Thermocycler apparatus according to claim 135 wherein there is one bias cooling channel and one ramp cooling channel proximate each row of sample wells.
Claim 141
Dependent Claim
47 words
Thermocycler apparatus according to claim 131 further comprising the apparatus according to claim 153 for holding up to 96 microtiter sample tubes placed in said metal sample block, and wherein the tops of said deformable caps protrude slightly above an uppermost edge of said two-piece plastic holder.
Claim 142
Dependent Claim
34 words
Thermocycler apparatus according to claim 137 wherein the downward displacement of said cover deforms the tops of said caps downwardly until the displacement is stopped by said uppermost edge of said two-piece plastic holder.
Claim 143
Dependent Claim
33 words
Thermocycler apparatus according to claim 138 wherein said uppermost edge of said two-piece plastic holder contacts the underside of said cover around the entire periphery of said edge, thus forming a gas-tight seal.
Claim 144
Dependent Claim
15 words
Thermocycler apparatus according to claim 131 comprising at least two heating zones forthe guard band.
Claim 145
Dependent Claim
312 words
A two-piece plastic holder for loosely holding up to 96 microtiter sample tubes of a preselected design, each having a cylindrically shaped upper section open at its top end and a closed, tapered lower section extending downwardly therefrom, each tube being of circular cross section and having a circumferential shoulder extending outwardly from said upper section at a position on said upper section below the open end thereof, comprising a. a one-piece tray member comprising i. a flat, horizontal plate section containing 96 holes in an 8-by-12 rectangular array compatible with industry standard microtiter plate format, said holes being slightly larger than the outside diameter of the upper sections of said tubes but smaller than the outside diameter of said shoulder, ii. a first vertical tray sidewall section completely around said plate extending upwardly to a height greater than the height of a tube resting in one of said holes, iii. a second vertical tray sidewall section around said plate extending downwardly approximately to the bottom of the upper section of a tube resting in one of said holes, b. a one-piece retainer releasably engageable inside said tray over any sample tubes resting in said tray comprising i. a flat, horizontal plate section containing 96 holes in an 8-by-12 rectangular array compatible with industry standard microtiter plate format, said holes being slightly larger than the outside diameter of the upper sections of said tubes but smaller than the outside diameter of said shoulder, ii. a vertical retainer sidewall section around said retainer plate section extending upwardly from said plate, wherein when said retainer is engaged inside said tray, the retainer plate section lies slightly above the shoulder of a tube resting in said tray and the first tray sidewall section is about as high as said retainer sidewall section, whereby tubes resting in said tray are retained loosely both vertically and laterally.
Claim 146
Dependent Claim
312 words
A two-piece plastic holder for loosely holding up to 96 microtiter sample tubes of a preselected design, each having a cylindrically shaped upper section open at its top end and a closed, tapered lower section extending downwardly therefrom, each tube being of circular cross section and having a circumferential shoulder extending outwardly from said upper section at a position on said upper section below the open end thereof, comprising a. a one-piece tray member comprising i. a flat, horizontal plate section containing 96 holes in an 8-by-12 rectangular array compatible with industry standard microtiter plate format, said holes being slightly larger than the outside diameter of the upper sections of said tubes but smaller than the outside diameter of said shoulder, ii. a first vertical tray sidewall section completely around said plate extending upwardly to a height greater than the height of a tube resting in one of said holes, iii. a second vertical tray sidewall section around said plate extending downwardly approximately to the bottom of the upper section of a tube resting in one of said holes, b. a one-piece retainer releasably engageable inside said tray over any sample tubes resting in said tray comprising i. a flat, horizontal plate section containing 96 holes in an 8-by-12 rectangular array compatible with industry standard microtiter plate format, said holes being slightly larger than the outside diameter of the upper sections of said tubes but smaller than the outside diameter of said shoulder, ii. a vertical retainer sidewall section around said retainer plate section extending upwardly from said plate, wherein when said retainer is engaged inside said tray, the retainer plate section lies slightly above the shoulder of a tube resting in said tray and the first tray sidewall section is about as high as said retainer sidewall section, whereby tubes resting in said tray are retained loosely both vertically and laterally.
Claim 147
Dependent Claim
27 words
Apparatus according to claim 141 wherein the holes in said tray section are countersunk and wherein the underside of the shoulders of said tubes are correspondingly beveled.
Claim 148
Dependent Claim
30 words
Apparatus according to claim 142 wherein the holes in the tray plate section and in the retainer plate section are larger in diameter than said tubes by about 0.7 mm.
Claim 149
Dependent Claim
44 words
Apparatus according to claim 141 wherein said tray member further comprises a plurality of support ribs extending along the underside of the tray plate member between rows of holes said ribs extending downwardly to the same extent as said second vertical tray sidewall section.
Claim 150
Dependent Claim
46 words
Apparatus according to claim 141 wherein said tray member further comprises a skirt section extending at least partially around said tray plate section and depending vertically from that section, said skirt section being adapted to fit into a guard band groove in a thermocycler sample block.
Claim 151
Dependent Claim
56 words
Apparatus according to claim 141 wherein said tray plate section has at least two openings provided therein and said retainer plate section has an identical number of vertical tabs, downwardly extending from said retainer plate, such that said tabs project through said openings and releasably engage the tray when said retainer is assembled with said tray.
Claim 152
Dependent Claim
47 words
Apparatus according to claim 146 wherein said tabs are disposed so as to form part of a skirt section extending downwardly at least partially around said tray plate section and wherein said tabs are adapted to fit into a guard band groove in a thermocycler sample block.
Claim 153
Dependent Claim
38 words
Apparatus according to claim 147 wherein said openings and said tabs are positioned such that said retainer and said tray are capable of only one orientation relative to one another when said openings and said tabs are engaged.
Claim 154
Dependent Claim
23 words
Apparatus according to claim 146 wherein said tabs are deflectable in a sidewise direction in order to come into alignment with said openings.
Claim 155
Dependent Claim
16 words
Apparatus according to claim 141 further comprising up to 96 microtiter sample tubes in said holder.
Claim 156
Dependent Claim
20 words
Apparatus according to claim 150 further comprising up to 96 deformable caps on said tubes for forming gas-tight seals thereon.
Claim 157
Dependent Claim
47 words
Apparatus according to claim 151 wherein each said cap has a downwardly depending cylindrical flange for forming a gas-tight seal with each said tube and a circumferential shoulder extending outwardly from said flange which prevents said flange from being seated on said tube below a predetermined point.
Claim 158
Dependent Claim
28 words
Apparatus according to claim 152 wherein the outer circumference of said downwardly depending flange fits snugly to form a gas-tight seal with the inner circumference of said tube.
Claim 159
Dependent Claim
39 words
Apparatus according to claim 151 wherein groups of 12 of said caps are linked together to form a single strand of caps which are suitably spaced so as to form gas-tight seals with up to 12 of said tubes.
Claim 160
Dependent Claim
64 words
Apparatus according to claim 141 further comprising a plastic base having 96 wells arranged in an 8-by-12 rectangular array, said wells being dimensioned to snugly accept the lower sections of up to 96 said sample tubes, said base being assemblable with said tray, said retainer and 96 of said tubes to form a microtiter plate having the footprint of an industry standard microtiter plate.
Claim 161
Dependent Claim
26 words
Apparatus according to claim 151 wherein said caps project above said first vertical tray sidewall section but are downwardly deformable to the height of said section.
Claim 162
Dependent Claim
16 words
Apparatus accoridng to claim 156 wherein said caps are deformable by heat and vertically downward force.
Claim 163
Dependent Claim
11 words
Apparatus according to claim 156 wherein said caps are resiliently deformable.
Claim 164
Dependent Claim
154 words
In a thermocycler apparatus suitable for performing the polymerase chain reaction, which thermocycler apparatus includes a metal sample block having an array of spaced-apart sample wells each of which has an inside surface, said wells being provided with one or more capped sample tubes each containing a sample mixture placed in a microtiter plate having an uppermost edge, which plate is seated on said sample block, a cover to enclose said capped sample tubes, which cover comprises a flat, horizontal rectangular portion and downwardly projecting skirt portions along the periphery thereof and further comprises a device for heating at least the underside of said horizontal portion, said cover being dimensioned to contact said sample block and to enclose said microtiter plate and capped sample tubes on said sample block when the tops of the capable on said sample tubes deform, due to the application of heat and a downwardly directed force on said cover.
Claim 165
Dependent Claim
154 words
In a thermocycler apparatus suitable for performing the polymerase chain reaction, which thermocycler apparatus includes a metal sample block having an array of spaced-apart sample wells each of which has an inside surface, said wells being provided with one or more capped sample tubes each containing a sample mixture placed in a microtiter plate having an uppermost edge, which plate is seated on said sample block, a cover to enclose said capped sample tubes, which cover comprises a flat, horizontal rectangular portion and downwardly projecting skirt portions along the periphery thereof and further comprises a device for heating at least the underside of said horizontal portion, said cover being dimensioned to contact said sample block and to enclose said microtiter plate and capped sample tubes on said sample block when the tops of the capable on said sample tubes deform, due to the application of heat and a downwardly directed force on said cover.
Claim 166
Dependent Claim
45 words
The cover of claim 159 wherein said side portions are dimensioned such that said skirt portions contact said sample block at substantially the same time as the underside of said cover contacts the uppermost edge of said microtiter plate as the cover encloses the plate.
Claim 167
Dependent Claim
36 words
The cover of claim 160 wherein the downwardly directed force is sufficient to ensure a snug contact between a lower portion of each sample tube and the inside surface of the well which contains said portion.
Claim 168
Dependent Claim
46 words
The cover of claim 159 further comprising knob and screw means for lowering said cover from one height to another, said knob and screw means including indication means for identifying a knob position corresponding to the cover height at which said cover contacts said uppermost edge.
Claim 169
Dependent Claim
51 words
The cover of claim 159 which provides sufficient heating to said capped sample tubes so as to heat the caps and the portions of the sample tubes positioned above the sample wells to a temperature above a condensation point of vapor from the sample mixture in said one or more tubes.
Claim 170
Dependent Claim
53 words
In a thermocycler apparatus suitable for performing the polymerase chain reaction having a sample well in which is seated at least one capped plastic sample tube containing a sample mixture, the improvement comprising a heated cover to aid in providing flush contact between said at least one sample tube and said sample well.
Claim 171
Dependent Claim
53 words
In a thermocycler apparatus suitable for performing the polymerase chain reaction having a sample well in which is seated at least one capped plastic sample tube containing a sample mixture, the improvement comprising a heated cover to aid in providing flush contact between said at least one sample tube and said sample well.
Claim 172
Dependent Claim
57 words
A disposable reaction container comprising a substantially conically shaped first wall portion and a substantially cylindrically shaped second wall portion, said first wall portion being adapted to contact along substantially its entire outer surface a correspondingly shaped portion of a heat exchanger, said first wall portion being substantially thinner in wall cross-section than said second wall portion.
Claim 173
Dependent Claim
57 words
A disposable reaction container comprising a substantially conically shaped first wall portion and a substantially cylindrically shaped second wall portion, said first wall portion being adapted to contact along substantially its entire outer surface a correspondingly shaped portion of a heat exchanger, said first wall portion being substantially thinner in wall cross-section than said second wall portion.
Claim 174
Dependent Claim
27 words
The reaction container of claim 165 which is adapted to receive a cap which forms a gas-tight seal when engaged over said cylindrically shaped second wall portion.
Claim 175
Dependent Claim
29 words
The reaction container of claim 165 wherein the angle defined by the longitudinal axis through said reaction container and the substantially conically shaped first wall portion is about 17°.
Claim 176
Dependent Claim
22 words
The reaction container of claim 167 wherein said first wall portion is from about 0.009 to about 0.012 inches in wall cross-section.
Claim 177
Dependent Claim
18 words
The reaction container of claim 168 wherein said second wall portion is about 0.030 inches in wall cross-section.
Claim 178
Dependent Claim
13 words
The reaction container of claim 165 which is made from an autoclavable plastic.
Claim 179
Dependent Claim
11 words
The reaction container of claim 170 which is made from polypropylene.
Claim 180
Dependent Claim
38 words
The reaction container of claim 165 additionally comprising a cap which is connected by a web to the reaction container and which is capable of forming a gas-tight seal with the upper portion of said second wall portion.
Claim 181
Dependent Claim
45 words
The reaction container of claim 172 having sufficient strength to withstand the application of a downward force to said cap when said cap is in place atop the upper portion of said second wall portion, which force is applied so as to deform said cap.
Claim 182
Dependent Claim
23 words
The reaction container of claim 165 which additionally comprises an annular flange which extends outwardly from the outside of said second wall portion.
References Cited (Backward Citations)
No citation records indexed.
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