throbber
November 22, 1999
`
`THE SCIENTIST • I 7
`
`NEVI LIDS ON THE BLOCK
`lABCONSUMER ANNUAL REVIEW OF THERMAL CYCLERS
`
`BY GRANT MEISENHOLDER
`
`S o much has changed in the last half-decade in the
`
`world of gene amplification. New breakthroughs and
`protocols have exceeded scientists' wildest expecta(cid:173)
`tions for applications of chis essential technology. ls there a
`single life science lab in the country without a che,mal
`cycler' From the high-end, ultrafast light-based cyders to
`the tiny personal cyders, there is a cycler to fit every need.
`Way back in the early years of PCR, "doing an amplifi(cid:173)
`cation" meant simply that-increasing the concentration of
`some target sequence of interest to use
`in insertion/
`ligation reactions. Quickly enough, scientists developed new
`ways to use the cycler. Now PCR-based methods exist for
`every aspect of biology that relies on genetic infonnation.
`Forensic, genomic, and evolutionary studies have ben(cid:173)
`efited greatly from tl1e technique known as random ampli(cid:173)
`fied polymorphic DNA (RAPD) PCR, which is used to
`fingerprint species from genomic DNA without prior
`sequence knowledge. Using arbitrary oligos, two c-ycles of
`PCR with low stringency are followed by forma l high(cid:173)
`stringency PCR with specific primers. The reaction is then
`followed by RFLP or comparative analysis.
`Touchdown PCR was developed to increase the yield of
`specific products. In chis method , the arU1ealing tempera(cid:173)
`ntre is lowered one degree every second cycl e to a lower
`li111it or "touchdown" temperature. This touchdown tem(cid:173)
`perature is then used for 10 cycles. This process ostensibly
`enriches for a specific product by ta king advantage of dif(cid:173)
`ferences in melting temperatures between correct and
`incorrect products by twofold per cycle. More recently,
`this technique has been adapted for genomic sequencing to
`elucidate DNA sequences from known peptide sequences.
`Long PCR is a method chat allows amplification of
`long stretches of DNA, from 0.5 to 20 kb. An enzyme mix
`containi ng both proofreading and polymerase activities
`al lows specific extension over great distances. \ Vhen used
`as an alternative to RFLP analysis, it shortens the process
`from six to eight weeks down to hours or days. It also may
`be used as an alternative to variable number of tandem
`repeats (VNTR) analysis.
`Chromosomal analysis has also benefited from PCR.
`DOP-PCR is a method that allows uniform amplification
`of sequences across a genome. Comparative DOP-PCR is
`used to detect chromosomal imbalances in genetic diseases
`· and evolutionary studies. Ampl ifi ed fragment length poly(cid:173)
`morphism-PCR (AFLP-PCR) is used to detect allelic loss
`in aging and otl1er studies. Single nucleotide polymor(cid:173)
`phi sm (Sl\'P) detection has made great strides with PCR.
`For hybrid cell studies resea rchers have developed Alu(cid:173)
`PCR to detect human chromosomes in the h vb rid cells.
`Scientists involved in the Human Gen.ome Project
`have made great use of the cycle sequencing method.
`Developed as an alterna tive to the Sanger method, PCR(cid:173)
`based sequencing uses femtomolar amounts of primers to
`start the elong-ation PCR, followed by sequencing. A
`major advantage is that chis method can be used for linear
`double-stranded DNA, unlike the Sanger method. It can
`aiso be used for cosmid, pl aque, and colony DNA
`sequencing.
`Scientists studying RNA expression have not been left
`out of the PCR craze. Using reverse a·anscriptase to pro(cid:173)
`duce cDNA gave rise to RT-PCR. This method has been
`used to diagnose a variety of infectious and genetic diseases.
`Histolog-ists quickly realized rhe advantage of having
`precise control over temperature and incubation time and
`adapted the cycler for use with in situ hybridization. One
`limitation of traditional ISH is detection of low-copy num (cid:173)
`ber Ri'\JAs. T his was overcome by the development of
`cycling-primed in situ (cycling PRINS) labeling-, which
`allowed researchers to gain deeper insight into me more
`ephemeral processes of the cell.
`PE Biosystems holds the exclusive license sights to the
`PCR technology. Anyone who wishes to perform automat(cid:173)
`ed PCR using certain reagents and machines must fi rst
`obtain a license. Fortunately, many reagents and machines
`include these rights in the purch ase price, but the user
`must check with the supplier before performing the ampii(cid:173)
`fication. This applies to research as well as applied fields. If
`the license is not supplied, PE Biosystems will provide one
`for a fee.
`This year's field of cyd ers includes many familiar
`names as well as some ingenious new models.
`
`Bio-Rad Bio-Rad's newest model is the iCvcler" ', which
`boasts NIST accuracy over its full teinper;ture range of
`
`±OSC and can be controlled by
`block, sample, or algoritlm1 meth(cid:173)
`ods. A 1/4-size VGA screen pro(cid:173)
`vides a simplified graphic interface
`and illustrates the c-ycling run.
`Real-time PCR is possible using
`the optional optical module.
`Th e Gene Cycl erT" is fully
`licensed for PCR and boasts a small
`footprint. Peltier heating and fan
`cooling keep cycling rates .high, and
`temperature accuracy is ensured
`tl1rough software algorithms. A
`heated lid is standard and 100 pro(cid:173)
`grams can be stored in memory.
`
`Cepheid's SmartCycler
`
`heated lids: standard (HLDX) and an ultralow condensa(cid:173)
`tion configuration model (HLDHP).
`The PowerBlock I (single block) and II (dual block)
`offer Peltier heating and a small footprint. 'l\vo program(cid:173)
`ming modes facilitate ease of use for simple ("Basic") and
`advanced ("Link") applications. The single-block model
`can be upgraded to dual blocks. Heated lids are optional.
`The water-cooled SingleBlock and Dua!Block systems
`are the workhorses of Esicomp 's line, with the flexibility to
`accommodate 0.5- and 0.2-ml tubes, microplates, and
`slides. The low-cost svstems feature NIST traceable accu(cid:173)
`racy, a five-year warr~nty, and across-the-block tempera(cid:173)
`ture uniformity of ±0.2"C. Optional items include heated
`lids and various block configurations.
`
`Genex Ltd. The small , uncomplicated Pacer cycler from
`Genex comes with a start and stop button and three LEDs
`to indicate cycling stages. This simple configuration is pos(cid:173)
`sible because all of the programming and storage is per(cid:173)
`formed on an accessory PC with me proprietary Preceptor
`software and then transferred to the machine before each
`run. Program storage space is limited, therefore, by the
`size of the computer rather than tl1e cyder's on-board
`memory. The Peltier-cooled block can hold 16 0.5-ml or
`20 0.2-ml tubes, two regular slides, or a mini 96-well plate.
`
`GL Applied Research The Genetic Thermal Cycler
`GTC-2 features two- and mree-step amplification ability,
`built-in programmable autoextcnsion, storage of up to 99
`protocols, and a 48-place sample block, among otl1er fea(cid:173)
`tures. Available options include a heated lid, a 96-well plate
`adapter, an 89-place sample block chat can hold up to 48
`0.5-ml and 41 0.2 -ml tubes, and a low-temperature module.
`
`Hybaid Hybaid has just launched its Multi block system to
`complement three already-established, stylish, individual
`cyders tl,at fit a variety of needs. All of its machines are PCR
`licensed, Peltier cooled, and calibrated to NIST standards.
`The attractive PCR Sprint is claimed to be the lowest(cid:173)
`priced licensed model available according to company lit(cid:173)
`erarure. It features fast ramping of up to 3°C/second,
`temperanire control from 4-99°C, user-friendly program(cid:173)
`ming, interchangeable blocks for 0.5 and 0.2 ml tubes, and
`a three-year guarantee. Hybaid's PCR Express speeds up
`reactions involving its AGS Gold DNA polymerase wim a
`one-second dwell time. Five control modes allow protocol
`flexibility-active/simulated tube, simulated slide, and
`simulated block. An autoadjusting heated lid allows use of
`any plasticware and oil-free PCR in rubes and plates.
`Alphanumeric programming and advanced editing fea tures
`simplify protocols, and four interchangeable blocks allow
`use of0.2-ml, 0.5-ml, flat-block, and 384-well fonnats .
`T he Omn-E c-ycler is a compact, multiformat, portable
`reactor with rhe ability to accommodate 0.2-ml, 0.3 -ml,
`and 0.5-ml tubes as well as 96-well plates. Active ntbe
`control and dynamic uniformity of ±0.5°C across the plate
`allow precision and reproducibility between samples and
`experiments. An optional heated lid is available for oil(cid:173)
`free cycling.
`In situ PCR protocols can be perfonned en masse with
`the Omnislide system, allowing simultaneous processi ng of
`
`Eppendorf's Mastercycler gradient model
`
`Cepheid T he SmartCycler"' uses a unique cooling/heat(cid:173)
`ing/optics/reaction module (the I-CORET") to perform
`amp lification reactions with real-time monitoring. The
`company is working on modules that "ill handle all phas(cid:173)
`es of sample preparation, reaction, and analysis, reducing
`the possibility of contamination.
`
`Corbett Research T he new Rotor-Gene Real-Time
`Thermal Cycler has two separate light sources to prevent
`spectral overlap in dual fluorescence studies. Samples can
`be loaded with reagents in the cap and reaction mix in the
`bottom of the tube. Centrifugal action mixes the samples
`and allows temperature unifo rmity. A 96-well adapter for
`use with Gene-Disks ,viii soon be available. Corbett also
`manufacntres a Gradient 96 Well Cyder for microplates
`and a High Speed Capillary Cycler, as well as Cooled and
`Ambient 96 \Veil Cyders.
`
`Eppendorf Scientific Instruments The Mastercycler®
`series is sold with the PCR license. The company's gradi(cid:173)
`ent model was the first on the market and offers a 96-
`position universal block chat can accept 96 0. 2-ml tubes, 77
`0.5-ml tubes, or one 96-well plate. Functions include selec(cid:173)
`table gradients (from I to 20°C), Peltier heating, adjustable
`ramping, time extension, touchdown, program linking, and
`pause. A heated lid is included. According to Vincent
`Prezioso, product manager at Eppendorf Scientific, me
`uniform-rate cooling aspect allows users to accurately
`reproduce optimized conditions for each cycling pattern.
`The standard version Mastcrcycler includes all of the
`same features as the gradient model (without the gradient).
`The Mastercyder personal has a 2 5-position universal
`block and offers most of the features on the standard
`model. Personal memory cards allow users to program and
`retain their own cycle profiles and transfer chem between
`any of the Mastercyder workstations.
`
`Ericomp The DeltaCycler 1 (single block) and II (dual
`block) systems are compact in design and use thermoelec(cid:173)
`tric heating and cooling to minimize the accessory tubing
`chat water-cooled models require. A range of 4"C to 110°C
`wim a temperature uniformity of ±0.2°C allows the full
`range of protocols to be used. Options inclu de two types of
`
`Agilent Exhibit 1227
`Page 1 of 4
`
`

`

`18 •THE SCIENTIST
`
`THERMAL CYCLERS
`
`November 22, 1999
`
`COMPANY
`
`PRODUCT
`
`SPACE REQUIRED
`WxDxH (CM)
`
`THERMAL
`CONTROL
`
`PCR
`LICENSE RIGHTS
`
`PROGRAMS/
`STEPS/ CYCLES
`
`HEAT RATE CQOL RATE
`(°C/SEC)
`( C/SEC)
`
`THERMA~
`RANGE ( C)
`
`BASE
`PRICE
`
`Bio-Rad
`800·424·6723
`www.bio-rad.com
`
`Cepheid
`408·541 ·4191
`www.cepheid.com
`
`Eppendorf Scientific Inc.
`800·421 ·9988
`www.eppendortsi.com
`
`Ericomp
`800·541-8471
`www.ericomp.com
`
`Genex
`44 1737 556617
`www.genex.ltd.uk
`
`GL Applied Research Inc.
`847-223-2220
`members.aol.com/glapplied/
`homepage.htm
`
`Hybaid
`888·449·2243
`www.hybaid-us.com
`
`GeneCycler™
`iCycler™
`
`27x19x16
`10x21x9
`
`Peltier
`Peltier
`
`Yes
`Yes
`
`100/5/300
`255
`
`SmartCycler™
`
`30x30x22
`
`LED/fan
`
`OEM
`
`150 programs
`
`Mastercycler®
`Mastercycler gradient
`Mastercycler personal
`
`DeltaCycler I System
`DeltaCycler 11 System
`PowerBlock I System
`PowerBlock II System
`SingleBlock System
`TwinBlock System
`
`26x41x27
`26x41x27
`18x35x25
`
`32x33x19
`32x44x19
`32x33x19
`32x33x19
`36x41x15
`36x51x15
`
`Peltier
`Peltier
`Peltier
`
`Peltier
`Peltier
`Peltier
`Peltier
`Resistive/water
`Resistive/water
`
`Pacer
`
`Call
`
`Peltier
`
`Yes
`Yes
`Yes
`
`No
`No
`No
`No
`No
`No
`
`No
`
`100/99/99
`100/99/99
`100/99/99
`
`26/99/99
`26/99/99
`26/99/99
`26/99/99
`26199/99
`26/99/99
`
`Unlimited
`
`1.5
`3.0
`
`7.0
`
`3.0
`3.0
`3.0
`
`1.3
`1.3
`1.6
`1.6
`1.3
`1.3
`
`2.0
`
`0.8
`2.0
`
`2.0
`
`2.0
`2.0
`2.0
`
`1.3
`1.3
`1.6
`1.6
`1.3
`1.3
`
`2.0
`
`Amb-97
`4-105 ±0.3
`
`Call
`
`Call
`
`OEM
`
`4-99 ±0.6
`4-99 ±0.6
`4-99 ±0.6
`
`4-110 ±0.5
`4- 110±0.5
`4- 110 ±0.4
`4-11 0 ±0.4
`Amb-110 ±0.5
`Amb-110 ±0.5
`
`Call
`
`Call
`
`$4,595
`$7,595
`$2,895
`$4,695
`$3,395
`$5,595
`
`Call
`
`GTC-2 Genetic Thermal Cycler
`
`46x63x48
`
`Resistive/water
`
`No
`
`99 programs
`
`1.0
`
`1.0
`
`0-99 ±0.5
`
`Call
`
`MultiBlock
`PCR Express
`
`PCR Sprint
`Omn-E
`
`Call
`23x39x25
`
`18x30x23
`19x28x19
`
`Peltier
`Peltier
`
`Peltier
`Electric/fan
`
`RapidCycler
`
`30x23x37
`
`Light
`
`Yes
`Yes
`
`Yes
`Yes
`
`No
`
`>100/10/99
`99/10/99
`
`60/5/99
`36/10/99
`
`99/-/99
`
`3.0
`Up to 3.0
`
`3.0
`Up to 2.0
`
`4-99 ±0.4
`4- 99 ±0.4
`
`Up to 3.0
`Call
`
`Up to 2.0
`Call
`
`4-99 ±0.5
`Amb +10 to 99
`
`Call
`$5,800-
`$6,310
`$2,495
`$1,995-
`$2,495
`
`TC 1600
`
`Call
`
`Electric
`
`No
`
`Call
`
`1.5
`
`1.3
`
`30-100
`
`Call
`
`10.0
`
`>5.0
`
`Call
`
`Call
`
`Tetrad
`DNA Engine Series
`MiniCycler
`PTC-100
`
`DNA Thermal Cycler 480
`GeneAmp 2400
`GeneAmp 9600
`GeneAmp 9700
`
`37x55x25
`24x33x24
`22x28x11
`24x28x27
`
`33x52x30
`34x60x21
`Call
`Call
`
`Pel1ier·Joule
`Peltier-Joule
`Peltier-Joule
`Peltier
`
`Cartridge
`Cartridge
`Film heater
`Peltier
`
`30x45x40
`
`Electric coil/air
`
`No
`No
`No
`No
`
`Yes
`Yes
`Yes
`Yes
`
`Yes
`
`400 programs
`200 programs
`80 programs
`340 programs
`
`Call
`
`Unlimited
`
`3.0
`3.0
`2.4
`2.5
`
`1.0
`>1.0
`1.0
`1.6
`
`20.0
`
`2.5
`Call
`Call
`Call
`
`1.0
`>1.0
`1.0
`1.6
`
`20.0
`
`Call
`
`Call
`
`·5-105 ±0.4
`·5-105 ±0.4
`·9-105 ±0.4
`0-100 ±0.4
`
`·5-100 ±0.5
`4- 99 ±0.5
`4- 99 ±0.5
`4- 99 ±0.5
`
`Amb-98
`
`$55,000
`
`Idaho Technology
`800· 735-6544
`www.idahotec.com
`
`Intelligent Bio-Instruments
`617-354·3830
`www.intelligentbio.com
`
`MJ Research
`888-735·8437
`www.mjr.com
`
`PE Biosystems
`800·345-5224
`www.pebio.com
`
`Roche Molecular Biochemicals LightCycler
`800-428-5433
`biochem.roche.com
`
`Snark Technologies
`800·966-7808
`www.snarktech.com
`
`St. John Associates
`800-837-2023
`www.stjohnassociates.com
`
`Stratagene
`800·424-5444
`www.stratagene.com
`
`Techne
`800·225-9243
`www.techneuk.co.uk
`
`Whatman Biometra®
`800·932-7250
`www.biometra.com
`
`Snark 64 and 96 models
`
`25x30x25
`
`Peltier
`
`No
`
`350/no limiUno limit
`
`4.4
`
`3.2
`
`0-105 ±0.5
`
`$3,495
`
`BioTherm BioDven Ill
`
`38x43x46
`
`Circulating air
`
`No
`
`99/20/20
`
`1.0
`
`1.0
`
`Amb-100
`
`$3,990
`
`RoboCycler® 40 & 96
`Infinity Temperature Cycler
`Gradient Temperature Cycler
`
`Genius
`Progene
`TouchGene
`
`Personal Cycler 20 & 48
`T3 Thermocycler
`TGradient
`TRIO Thermoblock
`UNO II Thermocycler
`T1 Thermocycler
`
`31x49x21
`31x49x21
`31x49x21
`
`22x42x24
`16x35x17
`22x42x26
`
`Call
`
`Robotic hot block
`Robotic hot block
`Robotic hot block
`
`Peltier
`Peltier
`Peltier
`
`Peltier
`Peltier
`Peltier
`Peltier
`Peltier
`Peltier
`
`Yes
`Yes
`Yes
`
`Call
`
`No
`No
`No
`No
`No
`No
`
`99/16/99
`99/16/99
`99/16/99
`
`99/9/99
`50/9/99
`3/3/-
`
`100/99/99
`Call
`100 per directory
`30/12/99
`Call
`Call
`
`2.8
`2.8
`2.6
`
`2.0
`>1.5
`4.0
`1.5
`3.3
`4.0
`
`1.8
`2.2
`1.6
`
`>1.5
`>1.3
`>3.0
`1.3
`2.4
`3.0
`
`No ramping
`No ramping
`No ramping
`
`No ramping
`No ramping
`No ramping
`
`25- 99
`25- 99
`25-99
`
`$6,995
`$5,495
`$6,995
`
`Call
`
`4- 99 ±0.5
`4- 99 ±0.3
`4-99 ±0.5
`
`Call
`
`Call
`
`Agilent Exhibit 1227
`Page 2 of 4
`
`

`

`November 22, 1999
`
`20 standard slides. A number of accessory fearures aid in
`processing and Aexibility.
`
`Idaho Technologies The RapidCyclcr from Idaho
`Technologies can amplify a 536 bp product in under 10
`minutes with a 30-cycle reaction. This speed is possible
`with a combination of photoheating, fan cooling, and thin(cid:173)
`walled capillary reaction tubes. Thin-walled microcen(cid:173)
`trifuge rubes may also be used. The reduced cycling times
`also resu lt in reduced amounts of nonspecific products.
`Cycling times can be increased by programming in hold
`steps as desired. The unit carries a one-year pans and labor
`warranty. An optional buffer system allows fini;hed sam(cid:173)
`ples ro be loaded directly onto a gel.
`
`Intelligent Bio-Instruments IBI offers the TC- 1600
`high -throughput cycle r. It is capable of running 16 blocks
`rota ! of 6, 144 samples
`in 96/192/384 -well
`for a
`rnicroplates. Four separate cycl ing profiles can be run
`simu ltaneously.
`
`MJ Research The latest offering from MJR is the PTC-
`200 DNA Engine. The sleek design and rugged chassis are
`suggestive of an Italian sports car. T nterchangea ble sample
`blocks and heat pump assemblies allow the user LO change
`format easily between runs while retaining l\TIST- traeeable
`accuracy. The .lab need only buy the single control unit and
`supp lement it with the desired Alpha modules, such as
`dual, independently controlled blocks, microplste format,
`or a slide adapter for up to 16 slides. Thermal control .is
`achieved by either block, in-sample probe, or calculated
`methods. Heating rates up to J"C/second reduce reaction
`times while ±0.4°C temperature homogeneity can be
`reached within 30 seconds at 90°C. The Hot llonnet heat(cid:173)
`ed lid controls pressure and height to accommodate vari (cid:173)
`ous plasticwares. A Power Bonnet is available for roboti c
`systems. Additionally, a sin gle cycler can be ne tworked to
`control up to J 5 separate instrnments. A PC can also con(cid:173)
`trol and monitor cyders remotely and export <laca to video
`screens or data bases in real time.
`For high-tluoughput applications or busy labs, the
`PTC-225 DNA Engine Tetrad may be tbe way to go. This
`allows up to eight separate blocks to run synchronous or
`ind ependent reactions. A compact footprint is maintained
`by housing the power supply separately outsid e the chassis,
`good for tight spaces or robotic applications. All of the fea(cid:173)
`tures of the PTC-200 are present in rhis model as well.
`The PTC - 100 cyders incorporate a Peltier h eati ng ele(cid:173)
`ment into a more economical model that can be config(cid:173)
`ured to accommodate plates, slides, or tubes. An optional
`heated lid is available as well as slide griddle adapters for
`amplifyi ng up ro four slides at a time. A large memory that
`holds up to 320 programs means that even crowded labs
`have ample programming space.
`For small labs or those that want an auxiliary cycler, rbe
`PTC-150 MiniCycler series may be just the ticket.
`Incorporation of the Peltier-Joule heat pump increases
`cycling speed with ramping rates up ro 2.4°C/second. The
`temperature may be programmed to allow refrigeration
`after completion of tl1e reaction. The compact, lightweight
`unit can be easily transported to different areas of the lab.
`Power failure protection resumes cycling after temporaty
`power loss up to 12 hours.
`1wo models are avai lable for in situ work. T he PTC-
`200/22 5 models mentioned above allow use of the Twin
`Tower block that can hold up to l6x2 slides. The PTC(cid:173)
`l00-L6MS is a dedicated configuratio n of the PTC-100
`series, able to hold up to J 6 double- or single-thickness
`slides. The sample block is made from oxygen-free copper
`milled from a single ingot and then plated in ni cke l for
`durability. Memory for 200 programs, power-failure pro(cid:173)
`tection, printer port, and a t,~.,o-year warranty are standard.
`
`PE Biosystems The GeneArnp® System 2400 comes stan(cid:173)
`dard with a heated lid for oil-free PCR and a 24-well sam(cid:173)
`ple block. Fast ramping and cooling with precise
`temperature control and across-the-block uniformity allow
`hig·h-quality, reproducible reactions. Tbe graphical inter(cid:173)
`face simplifies and speeds up programming. The
`GeneArnp 9600 offers many of the same features as the
`2400 but has a 96-we ll sample block.
`The newer GeneAmp 9700 comes in a variety of for(cid:173)
`ma ts. The blocks can be interchanged to accommodate 60
`0.5-ml rubes, 96 0.2 - ml tubes, a 96-well plate, or dual 384-
`well plates for high -throughput needs. The system features
`a sma ll footprint, PCMCIA card and RS485 communica(cid:173)
`rions ports, P eltier heating, graphical programming in ter(cid:173)
`face, and an optional MAX ,\.fode.
`Vlith the MAX Mode option, a user can choose
`between a varierv of software-driven modes. In 9600 emu (cid:173)
`lation mode, th; system follows cycling profiles like those
`found in the System 9600, achievin g an average heating
`and cooling rate of 3SC/sccond. Cnder Variable Ramp
`.\1.ode, the power input can be adjusted to all ow a range of
`ramping rates for specialized research applications. In Max
`Mode, heating and cooling rates can be increased up to
`5°C/second, and sample volumes can go up ro I 00 µJ.
`
`THE SCIENTIST • I 9
`
`The DNA Thermal Cycler 480 is designed for small
`sample volumes, reducing reagent cost. The system has a
`48-well block that uses 0.2-ml tubes and a two-tempera(cid:173)
`ture protocol for lower reagent requirements.
`The GeneA.rnp 5700 Sequence detection system cou(cid:173)
`ples the workhorse GeneAmp System 9600 with an optical
`detection syste1n and cornputcr to allov,,, the user to per(cid:173)
`form real-time PCR.
`
`operation. The RoboCycler Infinity has interchangeable
`40-, 96-, aod 384-well blocks. An in sitzt adapter is avai lable
`for d1e RoboCycler 40. The RoboCycler Gradient 40 and
`96 allow testing of up ro J 2 annealing temperatures in one
`run. A gradient range of up to 22°C across the block with
`a differen ce of up to re between adjacent wells can be
`programmed . All of tbc features
`included
`in
`the
`RoboCyclcr 40 and 96 are present as well.
`
`Techne UK Techne's Touch Gene cycler is a compact unit
`with a touchscreen display for easy interfacing. Multipl e
`block options allow labs Lo run a variety of protocols.
`Personal memorv cards let researchers store as manv as
`100 separate pr~grarns, and each program can lie p'ass(cid:173)
`word protected. Fast thermal cycling via Peltier h ea ting
`allows a 30-cycle program to be completed in less than
`one hour to increase overa ll throughput. A standard, uni(cid:173)
`versal _quick-release hea ted lid adjusts to keep th e opti(cid:173)
`mum pressure o n the samp le. The anricondensa tion skirt
`prevents sa mple loss onto the sid e walls and lid. An on(cid:173)
`board PRl ' sensor 1nonitors temperarure to 1naintain
`reproducibility berween samples and experiments. PC
`control is possible using the RS2 3 2 port and Gen Soft soft(cid:173)
`ware, allowing the researcher to print pro file information
`and choose, start, and stop programs.
`The Genius cycler also has multiple interchangeable
`block formats, with a larger block design for increased
`sample capacity and throughput. The display is a two- li ne
`LCD. The sp ring- loaded lid automatically adjusts the
`pressure to the optimum for the particular block and
`rubes . This unit also features external contro l through th e
`RS232 port.
`The low-cost Progene cycler features a very small foot(cid:173)
`print, high cooling and heating speed, wide thermal range,
`and a h eated lid. Two interchangeable blocks are avail(cid:173)
`able- one for 25 0.2-ml rubes and 5x5 multiwell plates and
`the other for 20 0.5 -ml tubes. A special feature is the abi l(cid:173)
`ity to program incremental/decremental segment holds for
`Long PCR and RAPD and incremental/decrementa l tem(cid:173)
`peramre for Touchdown PCR.
`
`Whatman Biometra® Whatman Biometra offers a wide
`range of cyders to suit most needs. The Tl Therrnocyder
`is the flagship model, wit!, a number of high-end features .
`Peltier heating brings fast ramping· speeds of up to 4'C/sec(cid:173)
`ond heating and 3°C/second cooling. Remote control of up
`to eight units is possible wid1 d1e avai lable PC software. Lid
`pressure is variable with "smart-lid" technology. A large
`display facilitates programming w ith the inntitive interface.
`Microplates can be sealed during the first cycle with the
`specially developed microplates and heat-sealing fi lm .
`The TGrad ient can create a wide tem peran,re gradi(cid:173)
`ent- up to 40°C across the plate. Many of the Tl 's fea(cid:173)
`tures are incorporated in this model, such as Peltier
`hearing, a gold-plated silver block, and an adjustable
`heated lid.
`
`The T3 Thennocyclcr builds upon
`the features found in the Tl to provide
`a platform with three independent
`blocks in a range of format options.
`Blocks are available with 20 or 40 wells
`and
`an
`18/48-well
`combination.
`Microplates, strips, and rubes can all be
`accommodated. As many as 150 pro(cid:173)
`grams can be stored in th e 1nemo1y. The
`heated lids can also seal microplates.
`The UNO II is a modular uni t fea (cid:173)
`Oiring four different in terch angea ble
`block configurations for pla tes, n1bes ,
`and slides. The gold - plated silver
`
`Roche Molecular Biochemicals' LightCycler
`
`Roche Molecular Biochemicals Roche has licensed the
`light technology from Idaho Technology and added some
`extra features to develop the LighrCycler. v\litb a combi(cid:173)
`nation of a fan and halogen bu lb to cool and heat thin(cid:173)
`walled glass capillary tubes, a reaction can be performed in
`less than 30 minutes. One feature tbat differentiates this
`product from Idaho Technology's is a built-in microvol(cid:173)
`ume tl.uorimeter that allows a user to perforrn real-time
`quantitative PCR. Additionally, a user can measure melt(cid:173)
`ing curves, detect rnutations, and simultaneously detect
`multiple
`targets. Programming and
`monitoring are done from a desktop
`PC, allowing unlimited user- defined
`complex protocol s.
`
`Snark Technologies For those looking
`li1nited budget,
`for performance on ,1
`Snark Technologies offers the Snark 64
`and 96 models. Both feature a heated
`lid , N1ST traceable accuracy (±OSC),
`fast heating and cooli ng rates (up to
`4°C /second), wide temperature range (0
`to lOS "C), para llel and seria l pores, a
`two-year warranty, easy progTammmg-1
`and a small footprint. Model 64 holds 64
`0.5 ml tubes while model 96 holds a
`
`microtiter plate or 96 0.2 -ml tubes. ----- block disperses heat uniformly while
`
`allowing fast heating and cooling. The
`adjustable pressure heated lid allows
`to be sealed
`microplates
`in situ.
`External PC control is possible with the
`available software.
`v\lharman's smallest model, the Personal Cycler has
`interchangea ble 20- and 48-well blocks. The unit holds
`l 00 programs and features pause (for hot scans) and
`adjustable ramping functions. A four-line, SO-character
`display allows information to be displayed in full rather
`than in shorthand notation. An optional heated Lid is avai l(cid:173)
`able. Documenta tion of the run is possible through the
`serial or parallel ports.
`Rapid ad vances in technology ensure that there is never
`a shortage of new machines to include in our an nual review
`of th ermal cyders. The accompanying table will help those
`in the marker for the newest models find the thermal
`cycler best suited to thei r individ ual needs.
`
`Sf. John Associates The BioOven III is Snark 64 thermal cycler
`one of the most unique cyders in this
`review. Heating and cooling are Jone by circulating warm
`or cool air in a chamber that contains a rotating sample
`rack that can be easily switched to accommodate a variety
`of sample rubes, plates, and slides. Up to 236 0.5-ml tubes,
`10 microtiter plates, 30 slides, o r hundreds of glass capil(cid:173)
`lary tubes can be loaded in each run. T he simplified menu(cid:173)
`driven interface also includes a format feature, which
`optim izes conditions based on the type of sample being
`run. A serial port allows users to program, format, and
`access data from ao external con1puter.
`
`Stratagene The RoboCycler® is another innovative
`design. The rohot arm moves th!! samples from one pro(cid:173)
`grammable heat block to another. Despite the seeming
`delay in physically moving the samples from one block to
`another, cycling- times arc actually reduced since the block
`doesn't have to change tempera ture also. This also trans(cid:173)
`lates to even heating of the block, allowing very right tl1cr(cid:173)
`rnal uniformity across th e block and between samples
`(±0.1 °C). An optional heated lid allows oil- and wax-free
`
`Grant .,teisenholder can be contacted r,r f!,Vneisen holder@
`t be-scie1 ztfrt. com.
`
`For More Information
`Circle Rc,1dcr Sen:it.:c #74
`
`Agilent Exhibit 1227
`Page 3 of 4
`
`

`

`Please Note: The contents of the attached document are
`copyrighted works and may not be shared. You have secured
`permission to use this document for the requested purpose below:
`
`(cid:82)(cid:101)(cid:103)(cid:117)(cid:108)(cid:97)(cid:116)(cid:111)(cid:114)(cid:121)(cid:32)(cid:83)(cid:117)(cid:98)(cid:109)(cid:105)(cid:115)(cid:115)(cid:105)(cid:111)(cid:110)
`
`To the extent that a publisher or other appropriate rights-holder has
`placed additional terms and conditions on your use of this
`document, such terms and conditions are specified herein under
`“Copyright Terms”.
`
`This coversheet may not be removed from the article without
`permission from the Information Center. For permission to share
`this article please contact the Information Center at
`infocenter@thermofisher.com or 815-987-4625.
`
`Thermo Fisher Information Center
`
`infocenter@thermofisher.com
`
`(815) 987-4625 tel
`(815) 968-7316 fax
`
`Information Center on iConnect
`CIA 2.0
`
`Agilent Exhibit 1227
`Page 4 of 4
`
`

This document is available on Docket Alarm but you must sign up to view it.


Or .

Accessing this document will incur an additional charge of $.

After purchase, you can access this document again without charge.

Accept $ Charge
throbber

Still Working On It

This document is taking longer than usual to download. This can happen if we need to contact the court directly to obtain the document and their servers are running slowly.

Give it another minute or two to complete, and then try the refresh button.

throbber

A few More Minutes ... Still Working

It can take up to 5 minutes for us to download a document if the court servers are running slowly.

Thank you for your continued patience.

This document could not be displayed.

We could not find this document within its docket. Please go back to the docket page and check the link. If that does not work, go back to the docket and refresh it to pull the newest information.

Your account does not support viewing this document.

You need a Paid Account to view this document. Click here to change your account type.

Your account does not support viewing this document.

Set your membership status to view this document.

With a Docket Alarm membership, you'll get a whole lot more, including:

  • Up-to-date information for this case.
  • Email alerts whenever there is an update.
  • Full text search for other cases.
  • Get email alerts whenever a new case matches your search.

Become a Member

One Moment Please

The filing “” is large (MB) and is being downloaded.

Please refresh this page in a few minutes to see if the filing has been downloaded. The filing will also be emailed to you when the download completes.

Your document is on its way!

If you do not receive the document in five minutes, contact support at support@docketalarm.com.

Sealed Document

We are unable to display this document, it may be under a court ordered seal.

If you have proper credentials to access the file, you may proceed directly to the court's system using your government issued username and password.


Access Government Site

We are redirecting you
to a mobile optimized page.





Document Unreadable or Corrupt

Refresh this Document
Go to the Docket

We are unable to display this document.

Refresh this Document
Go to the Docket