LabConsumer
`
`Some Like It Hot: A Thermal Cycler Roundup
`
`Former ht'gh—endfeatures are standard
`options in the newest thermal Cycfers
`Bv AILIEII Conrrnlts
`
`lids featuring automatic
`pressure control
`for
`reli-
`able sealing and protection
`of tubes.
`
`It was bound to happen. During the growth of PCR,
`
`many companies joined the tltemtal cycler bandwagon.
`But since The Sct'ertti.r.r'.r last
`thennal cycler review.‘
`some of these manut'acturers—such as Ericomp——l1ave left
`the cut-tl-trnat market and a number of the machines listed
`in previous LabConsumer profiles have been discontinued.
`Market niches remain for those companies and product
`lines that have survived the intense competition.
`One. such niche is real-time therrnocyclers, previously
`reviewed in The Scr'entr'.rt.1 These cyclcrs permit
`researchers to monitor the thermal and optical properties
`of their reactions in real time. and are indispensable for
`quantitative PCR. Another specialty is high-throughput
`PCR. spurred by the rapid growth of genomics-related
`research. Overall. features that were once optional. such
`as heated lids. are now standard, and interchangeable
`blocks allow researchers to customize their experiments
`even with low-end thermal cycler models.
`Although the number of Companies manufacturing
`thenna] cyclers may be on the decline. the number of
`options available to researchers is not. From basic labo-
`ratory PCR workhorses to real-time and hjgh—throughput
`machines. the latest batch of Lherntal eyelets will certain-
`ly heat
`things up in the lab this coming year. What
`follows is an alphabetical
`round up of therrnocycler
`providers:
`
`Applied Biusystems: Foster City. Calif.-based Applied
`Biosystcms holds the patents on thermal cyclers. along
`with the exclusive license to the PCR process,3 and offers
`researchers several PCR options. The CrEtll3Al'l'lp® PCR
`System 9'r‘0l} is designed for high sample volumes and
`comes in fit]-wellll].5 ml, 334-well. and 96-well fonnats.
`The GeneArnp PCR System 2400 is a personal—sized
`cycler that features a heated lid and a 24-well sample
`block. The GeneAmp PCR System 2700 includes many
`of the features of the 9700 system but
`in a smaller
`footprint. For
`the real-time PCR market. Applied
`B'tosystcn1s' AB] PRISM‘? 7700 Sequence Detection
`System features a built-in thermal cycler and the ability
`to detect multiple fluorophores in :1 single tube.
`
`Biomctra: Gortingen. Gennany-based Eiiometra offers a
`variety of Peltier-based cyclers, ranging from personal-
`sizcd to high throughput. (The Pelticr effect transfers
`heat from one side of a seiniconductor to another. creat-
`ing an efficient heating and cooling system without
`refrigerants or compressors] The Tpersorrnt then'nocy-
`cler
`features three different block fon11ats-48-well.
`20-well. and cornbi-block. Each format handles tubes.
`strips. and microplates. The TGm.:ft'ent
`thermocycler
`allows fast optimization of new reactions with a thermal
`gradient of up to 40°C. The Tl‘ thermocycler offers a
`heated lid. gold-plated silver block, and heating and cool-
`ing rates of -l‘C per second and 3°C per second,
`respectively. The T3 thcrmocycler, the successor to the
`company's TRIO model. offers a choice of three formats:
`3 X 48 wells. 3 x 20 wells, and a combi-blocl-t with 3 it 13
`and 3 x 48 wells. The T3 also features three independent
`blocks with adjustable heated lids. allowing the user to
`run experiments with different sample sizes and formats
`in the same instrument. The TROBOTIl’IerI'noCycler is the
`newest addition to Biome.tra's cycler range. It is compat-
`ible with a variety of robotic systems and offers a
`motorized heated lid and a small footprint. The motor-
`ized plate lifter ensures easy removal of plates by a
`robotic arm. All Biorrtetra thermal cyclers have heated
`
`32 The Scientist
`December 10. 200}
`
`Bio-Rad Laboratories:
`Hercules.
`Calif.-based
`Bio-Rad
`offers
`the
`iCyc|er"” Themtal Cycle.
`3 flexible. modular system
`that easily upgrades to real-
`time
`quantitative
`PCR
`capability and also offers
`optional gradient capability to
`facilitate reagent optimization.
`The optical
`real—ttme detection
`system upgrade is a modular unit
`that installs directly over an existing or new iCycler unit.
`The resulting ifjycler iQ system is designed as an open
`platform. capable of detecting a variety of different
`chemistries,
`including DNA binding dyes. Roche
`Molecular Systems‘ TaqMan®. molecular beacons, dual
`FRET. and primerbased technologies. The optical design
`promotes the multiple.\ct.l analysis of up to four different
`fluorophores without compromising sensitivity or
`dynamic range. Eio—Rad also offers a personal-sized
`cycler. the Gene Cycler, which features a small footprint
`and a heated lid.
`
`Instruments: Westbury. NJ’.-based
`Br-inkmann
`Brinknranns Eppendortw Mastercyelcrfll line of thermal
`cyclers includes both personal-sized and gradient mod-
`els. All feature heated lids and are sold with a PCR
`license. The gradient model provides constant ramping
`rates (S£eadySlope"“" technology} so that programs opti-
`mized on the instrument can be used on non—gradient
`machines.
`
`Cepheid: According to company president Kurt
`Petersen. Sunnyvale. Calil'.—bascd Cephcid has sold
`l'l'lU'l'|'.'
`than 400 Smart Cyclerfl’
`instruments since the
`product was launched in May 2000. The system is based
`on the company's l—CORE® tcchnology——mjcrofluidics—
`based. temperature-controlled modules that permit each
`sample to be subjected to different experimental condi-
`tions. Petersen explains that the Smart Cycler is the only
`real-tirnc system on the market that offers this "random
`access" capability, a feature that speeds up assay opti-
`mization by allowing researchers to operate each reaction
`site independently of the others. Each I-CORE unit can
`examine up to four targets in a reaction tube. thus facili-
`tating multiplex reactions.
`
`Curhelt Research: For gadget-loving researchers.
`Corbett Research of Sydney. Australia offers the Palm
`Cycler, an individual -sized thermal cycler integrated with
`a Palm PC. The instrument offers a gradient function fea-
`turing a true gradient from I-53 degrees across the block.
`Corbctt’s Rotor—Gene, a
`real-timc PCR system, can
`detect :1 variety of chcmistrics including SYBR Green 1
`[from Eugene. Ore.-based Molecular Probes), Taqlvlan.
`and molecular beacons, and can detect four different flu-
`orescent prubes in a single tube. The Rotor-Gene
`maintains temperature homogeneity via a centrifuge
`rotor that spins the samples at 500 rpm.
`
`Idaho Technology Inc.: This Salt Lake City based com-
`pany's latest offering is the Indy“ Air Thermocycler,
`which uses air cycling to decrease ramping and cooling
`ti me; a 30-cycle, three-temperature reaction can be com-
`plelcd in less than 35 minutes. Unlike the company's
`flagship RapidCycler®. which uses a similar cycling
`technology but is limited to capillary tubes. the Indy ther-
`
`
`
`CourtesyoiBtlnkrrrannInstruments
`
`Brfnkmann's Eppendorf Masterqrcler fine of thermal
`cycler: includes gradient and personal-sized models.
`
`mocycler is designed for standard 24 it 0.2-ml PCR
`tubes. According to company representative Nathaniel
`Lallatin, the Indy thermocycler's speed and small foot-
`print make it
`ideal for research laboratories that are
`trying to increase throughput but do not wish to invest in
`a more expensive.
`large-:—capacity machine.
`Idaho
`Technologys popular RapidCycler model
`is still avail-
`able and is actually faster Lha.rt the Indy cycler owing to
`the higher heat conductivity of glass capillary tubes;
`however. researchers may find that standard PCR tubes
`are easier to use.
`
`Marsh Bio Products: Rochester. N.'x'.—based Marsh
`offers two Duncan thermal cyclers. each utilizing a water
`bath for thermal control. The DT—M and DT-I08 instru-
`ments can accommodate 24 or I08 rnicrotilcr plates
`respectively. Since these instrtttnents use water baths for
`temperature control. they exhibit small weil~to—wel] tem-
`perature variability, according to David Witkosl-ti,
`Marsh’.~; marketing communications manager. The
`Duncan thermal cyclers are robotic—bascd and are mostly
`found in pharmaceutical and biotechnology companies.
`
`MatriCal: Chadds Ford. Pa.-based MatriCal developed
`the MatriCycler‘“ for
`the company's specialized
`Man-iPlatesW, which are designed to optimize the shape
`of hi gh-throughput wells for increased signal detection
`and ease of liquid handling. According to company liter-
`ature. researchers using the Mat1'iCyclcr with the plates
`can increase their throughput up to I00 percent, with a
`reduction in reagent use of approximately 80 percent.
`Company co-founder Kevin Oldenburg explains that the
`MatriCycler overcomes four problems associated with
`the use of traditional cyclers for high-throughput experi-
`ments. First, the heating block of a conventional cycler is
`a large thermal mass that takes a long time to heat and
`cool. Similarly. the plastic used in rt1ulti—wcll plates is
`thermally insulated and therefore takes time to heat.
`Because plastic tends to deform upon heating. the plates
`tend to warp and become wedged into the machine. pre-
`venting easy removal. Finally. reactions using multi-well
`plates require the use of a heated lid to prevent evapora-
`tion:
`this often results
`in the development of a
`temperature gradient across the plate.
`The Matt-iCycler works by healing each sample well
`with a thermally conductive probe. rather than relying on
`the thermal block to heat the samples. This eliminates the
`problem of sample evaporation, speeds up sample heat-
`ing, and. according to Oldenburg. provides a heating rate
`of up to 2G"C per second. Thus. a 30-cycle reaction takes
`20-30 minutes to complete with this instrument.
`
`MJ Research lnc.: Ml Research {MlR) of Waltham.
`Mass.. has added a number of new items to the world of
`thermal cyclcrs. All of the company's cyclers feature
`Peltier heating and Alphall“ modules.
`interchangeable
`
`THERMO FISHER EX. 1030
`
`

`
`healing blocks that allow users to change sample forrnat
`rapidly. MIR offers ll) dillcrcnt Alpha units for formats
`ranging from 0.5-ml PCR tubes to microwell plates to
`microscope slides; one of the more unique products is a
`set of microscope slide blocks that allow users to run a
`total of 3! slides at a time for in situ PCR. The DNA
`Engine‘-“ cycler. the company's “workhorse" model. lea-
`lurcs a heated lid and independent dual blocks to allow
`two experiments to be run simultaneously. The Dyadm
`thermal cycler. one of the newest members of the MIR
`family. allows four separate protocols to be run at the
`same time with the use oflwo Alpha modules. It also fea-
`tures an easy-to—usc. Windows—driven, graphical user
`interface. The newer Tetradm model oliers the same fea-
`tures as the smaller DNA Engine“ cyclcr. but is capable
`of handling four times as many samples. All units feature
`a heated lid and are roboticcompatible. For more modest
`budgets, MJR ofl'r:rs a number of personal-sized cyclcrs,
`including the Mini-Cycler and P'TC-lDl]'”" thermal
`cycler. These cyclers feature Hot Bonnet"" heated lids
`and can be used for a variety of sample formats.
`MIR‘: recently released DNA Engine Opticonl“ is a
`real-time cyclcr that uses fluorescent detection to moni-
`tor reactions. The system is essentially a DNA Engine
`chassis coupled to a 96-well Alpha unit and an optical
`detector. According to vice president of sales and mar-
`keting Mike Mortillaro. the Upticorl is the only 96-well
`real time system on the market that involves no moving
`pans yet allows the instrument to view each sample or
`well independently. A photomultiplier tube detects sig-
`nals from samples
`individually. "One of the big
`advantages that we see in the Opticon’s design is that
`we're looking at each sample independently and individ-
`ually. and we have much lower cross-talk. That gives us
`a broader dynamic range and a higher level of sensitivi-
`ty." says Mortilluro.
`
`MWG-Biotech AG: Ebcrsburg, Germany—bascd MWG,
`offers the Primus system. a multi-block cyclcr that
`is
`designed as at four-block. stand-alone unit but can also be
`interfaced with up to 30 individual blocks via PC soft-
`ware. The. system also features a patented ltigh—pressure
`lid that. unlike other heated lids. prcvcnts evaporation of
`reaction volumes from 384-well platcs. Standard heated
`lids were developed to promote temperature homogeneity
`across the block. but were designed when scientists were
`still using individual microfuge tubes with caps. says
`Craig Abrahms. president of High Point. N.C.-based
`MWG Biotech lnc..
`the company's U.S. subsidiary.
`However. in today‘: higher-throughput market where sci-
`entists use rnicroplales. they cannot" be fully scaled or
`capped easily. “So these same hcuted lids
`are now pro-
`moting evaporation." explains Abrahams. The Primus
`cyt:ler's. high-pressure lid provides up to 300 Newtons of
`pressure. making it effective for evaporation protection.
`According to Abrahams. the Primus system has been pop-
`ular with high-thmughput labs looking for high capacity
`instruments at a low cost. For example. Graham Casey.
`a
`researcher at
`the Cleveland Clinic Foundation in
`Cleveland, Ohio. recently purchased three of the multi-
`blocit instruments and says that he has been “pleased with
`all of the machines." Laura Bcdzylt. staff biologist at
`Wilmington, Del.—baserl DuPont Co., has been using the
`Prirnus thermocycler in her research for almost two years
`for generating PCR products for DNA microarrays;
`Bedzyk says that the factors influencing her decision to
`purchase this insutiment included “multiple. independent
`positions. pressurized lids. ease of use. and the potential
`for incorporation into a custom. automated system."
`
`lndianapolis—based
`Roche Molecular Biochemicals:
`Roche has licensed Idaho Tcchnology‘s thermal cycler
`technology and reengineered it
`for the L'tghtCyclerT'~'
`insuumcnt. a real-time thermal cyclcr that. like Idaho's
`RapidCyc|cr. employs circulating air and glass capillary
`tubes to dramatically reduce amplilicaiion limc. The sys-
`tem uses fluoresccnt detection for real—time analysis and
`is controlled by a PC‘ wt1rk5lill.it'J1'L Researchers can use
`the LightCyt:ler
`for assays using SYBR Green I.
`
`LabConsumer
`
`Tecltnc‘s Touchgene® Gradient Thermal Cyclcr is adver-
`tised as the most linear gradient cycler on the market—it
`is linear over a 30°C‘ range —and offers real-time graplti
`cal display and 2 touch—sensitivc screen for case of
`programming. To
`ensure
`block
`uniformity,
`the
`Tottchgene cyclcr includes four temperature sensors per
`block. All Techne cyclers come standard with adjustable
`heatcd lids and interchangeable blocks.
`
`Roche‘: ljghrfycler instrument uses circulating air and
`glass capillary tubes to reduce amplification time.
`
`scqucncc—speciftc hybridization probe pairs. or several
`other detection l"ormats.3
`
`St. John Associates: Bcltsville. Md.-based St. John's
`BioDven Ill Them-tocycler is based on circulating air
`technology but is capable ofhandling samples in a vari-
`ety of formats,
`including standard PCR tubcs. glass
`capillary tubes. slides. and rnultiwcll plates. Designed
`t'or very high capacity. the BioOven Ill cycler can han-
`dle ill multi—\-vell plates per run and features a rotating
`carousel to ensure temperature uniformity. According to
`Peter St. John. the BioOven Ill cycler enjoys populari-
`ty with seientists in a variety of
`fields including
`agribusiness.
`forensics. and pharmaceutical
`research.
`because it offers greater well—to-well uniformity than
`aluminum block cyclcrs and provides higher flexibility
`in terms of sample media.
`
`Jolla. Calif.-based Slratagentfs
`Stratagertc: La
`RoboC‘yclcr
`features
`four programmable blocks and
`offers it gradient feature to simplify optimization. What
`makes this cyclcr unique is that it employs a robotic arm
`to move samples from block to block. The user can set
`three of the four blocks to denaturation. annealing. and
`polymerization temperatures; the fourth is a cooled stor-
`age block. Because samples are moved rnhotically to the
`appropriate temperature block for each point in the reac-
`tion. there is no need for temperature ramping of a given
`block. According to company literature.
`this method
`reduces experiment time up to 30 percent. Product man-
`ager Peter Pingerelli cxplains that the popularity of the
`RolJOCycler stems from its durability. Competing instru-
`ments. he says. "have had a lot of problems. with
`he-avy—use instruments [failing] post-warranty."
`Stratagcne's Mx4tJ(J0T"' Multiples Quantitative PCR
`System, introduced last year? offers llttoresccnce-based
`real-time detection and can measure up to four dit‘ferertt
`dyes in a single tube. The system uses a quart.~:—tungstcn
`halogen lamp rather than a laser light source. broadening
`the excitation wavelength range.
`it also features a PC
`interface and. according to company literature. tempera-
`ture control that exceeds the industry standard.
`
`Techne: Princeton. NJ.-based Techno offers a range of
`cyclers to tit different research needs and budgets. The
`Tcchgene"9 cycler. a Pcltier—bascd system that replaces
`the company's Progeneg‘ model. is a compact. inexpen-
`sive instrument that researchers can run remotely through
`a PC. Although the Techgene cycler is designed for a low
`sample quantity (2tL35 wells). up to 32 units can be
`linked for larger experiments. The Flcrtigene“—" cyclcr.
`which will replace the company's Ge.-nius® model.
`is a
`Peltier—brtsed system designed for higher throughput.
`
`Thermn Hybaid: Franklin. M:tss.—based Thermo
`1-lyttaid‘:. cyclcrs. which range from individual-sized to
`mu|1i—block networks. come in a variety of formats.
`The company's most basic system. the PCR Sprint. fea-
`tures Peltier heating. a 20-24 sample individual block,
`and two different block format options. Titermo
`Hybaid‘s PCR Express and soon-to—bc—rc1cased Prtll.
`also Peltier-based machines. feature six different inter-
`changeable block options. including a flat block for in
`situ or microarray experiments. The Pxll also includes
`Tlterrnu Hybahfs new last block technology and :1
`large graphical display panel.
`The company‘s Multililock System (MES) is a flexi-
`ble thermal cycler system driven and monitored by at
`central PC that features software. which allows real-time
`monitoring and automatic logging for good laboratory
`practice lGl.Pi purposes. By enabling up to 30 individual
`blocks to be attached to a single processor. users pay less
`per block than they would if purchasing individual stand-
`alone machtnes. And. unlike the multi—bloclt systems
`from MJR and MWG, Thermo Hybaid‘s system allows
`the user to purchase blocks individually. The company's
`newest product
`is
`the MES“.
`the
`fully robotic
`Multil3lock. which facilitates high-throughput PCR.
`According to the company. by ejecting the whole block
`through the front of the unit, the MES“ is fully stackable
`and integrates easily into robotic systems. E
`Ailetm Corrsrtzrrs can be carilarred ur
`r:1t:'tm.t‘.mn.<@the-scir'rrrEst.c'om.
`References
`I. C-. Metsenholdcr, "New lids on the blucl-t.“ The 5t'l:'flllFt.
`Nov. 22. ‘£999
`2 D. Fitzgerald. "Up to speed on PCR." Fire Scicrtrisr.
`27. Zfllltl.
`3. A Constarts. "Court: Lilhl clouds mt-r PCR prrctng." The Sdenrtrr.
`Ii[l3|’.l.St.-pi 3.2001
`
`l-'1[2.'l-i'.'-ll. Nov
`
`|3I33]:l7.
`
`5:. John '5 Biooven lull‘ tfterrhot.-ycler offers
`flexibility in terrns ofsample fom-rats.
`
`The Scientist
`December 10. 200]
`
`THERMO FISHER EX. 1030
`
`

`
`LabConsumer
`
`Suppliers of Thermal Cyclers .
`
`Applied Biosystems
`(800) 345-5224
`wwwiappliedbiosystemsxcom
`
`Biometra
`+ 49 (551) 50 53 6 0
`www.biometra.wm
`
`8iD—Rad
`(BUD) -12:1-5723
`www.hio-rad.corn
`
`Brinkmann
`[800] 645-3050
`l'\fL\I\'\(.bHI1|(l11£I|1l1‘COITI
`
`Cepheid
`(888.1 838 3222
`W\.I‘nf\I'IJ'.SfT1al'[(}r(|EF.[fJITI
`Corbett Research
`+61(2)‘3?36132[|
`wwwmrbemesearclmcom
`
`GL Appiied Researth
`[S-17) 221222
`
`Idaho Technomgy
`(300) 735-65¢!-1
`www,id;ul1otr:ch.com
`
`IIIfluI(ydaI 3|!
`
`nu Ila’-an: nml :-gi-i
`
`Hvfiflfluflfl
`
`34 The Scientist
`December [0, 200;‘
`
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`
`THERMO FISHER EX. 1030
`
`

`
`LabConsumer
`
`Suppliers of Thermal Cyclers (continued)
`
`Marsh Bio Produnr.
`(S0l'J}- S-2812
`\.wv\.1.rm. _:h|)iu.cum
`
`MntIiC.!l
`(610; 361-8867
`www_mat
`. ' '
`MJ Researclu
`(333) pgg | [R
`w\r»rw.n1jr.ccm1
`
`Maiuuluwt
`
`-
`
`.
`
`kn$IuIIoli'(
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`
`Imma
`
`H51
`
`IJIU. E-plirnl tyda
`
`um:
`
`«fr EI.3°(
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`5—III5"t
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`
`fl
`
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`
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`-
`
`7
`
`V
`
`L
`
`um
`
`+1-on
`
`-S-lDS“t
`
`Nlh"HG Bicm_-ch
`(Sm 694-2332
`www.r11wgl3Iul«::;h_cL1m
`Rncim |'v'\n\c-‘L11 N‘ Binilwmicals
`[(500) 262-1
`|Jiochen1.roche_cum
`St, John Agsocnatea
`{8flD" S3?-2023
`uw.w.st1oi1n.1ssoci.aLes.corn
`Stralngene
`(800) ¢2=‘1—54:'l«'l
`www.5trat.:ugene.com
`
`Tecime
`(800) 225-9243
`VL"l'\r\.'V‘IEC|'II'H'3LIS:].CE|l‘I‘!
`
`Thermo Hybaid
`(3881 =1—HYBA|D
`u\mrw.t h ern10I13.r|_1.:3 i d. r. um
`
`Inhiydu Emliuu Turqnunm
`tgdnsillflfiil
`
`Editors Note: To the best of our knowledge, this tabie is a comprehensive fisting of suppliers.
`
`The Scientist
`December 10, 2001
`
`THERMO FISHER EX. 1030
`
`

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