Up On Blocks: A Profile Of Thermal Cyclers With Interchangeable Blocks

Date: October 12, 1998Comparison Table Bench space and budget--the two biggest limiting factors of life in the lab. How can both be maximized, especially in terms of equipment? This problem undoubtedly occupies the time and efforts of all life scientists at one time or another. Often, easy answers are difficult to find. In this profile, LabConsumer looks at one of its favorite topics, the thermal cycler, for a glimpse at how the manufacturers of these products have tackled the space and budget problem and expanded the versatility of their instruments as well. The versatility provided by interchangeable-block thermal cyclers has many applications. Research and development labs, for instance, benefit from the choice of sample formats, and multiple users can use one base unit for a variety of DNA amplification jobs, including in situ PCR. Dedicated sample blocks also prevent sample cross- contamination with radioactive or other sensitive materials. Stratagene Product Manager Douglas Drake explains another driving force behind interchangeable blocks. "The high-throughput demands placed on thermal cyclers by the human genome product," he says, "have pushed the industry to expand instrument versatility without requiring the customer to buy new instruments." These pressures have resulted in the recent introduction of interchangeable modules that accept 384-well plates, such as Stratagene's RoboCycler Infinity and the dual 384-well GeneAmp PCR System 9700 from Perkin-Elmer. Other cyclers have even greater capacities, such as MJ Research's PTC-225 DNA Engine Tetrad, which runs up to 1,536 simultaneous reactions, and St. John Associates' BioOven III, which is a forced-air cycling oven that handles a whopping 8,640 reactions in the form of ten 864-well plates. The application of the solid-state heat pumping phenomenon called the Peltier effect to thermal cyclers has led directly to their ability to use interchangeable blocks. This effect was named after the Frenchman, Jean Peltier, who first described it in 1834 after observing the absorption and release of heat when an electric current was passed through dissimilar metals. The development of the Peltier technology and its application to thermal cyclers in the 1980s freed refrigerated thermal cyclers from the restrictive tubing connections required to pump chilled liquids through the sample blocks. Because the Peltier heat pumps are frequently incorporated into the sample blocks themselves, the blocks became readily exchangeable. For most of the instruments profiled here, the blocks simply slide in and out without the use of tools. Most of the currently available interchangeable-block thermal cyclers are sold with one block as part of the package, although others require the separate purchase of a sample module. Prices for the thermal cyclers run from $2,055 to $14,995. Interchangeable blocks cost between $200 and $5,395. Here's how 14 interchangeable-block thermal cyclers from eight manufacturers stack up: Biometra's UNO-Thermoblock Biometra (a Whatman Company) Personal CyclerUNO-Thermoblock™UNO II Thermocycler Distributed exclusively in the United States by LabRepNet, the three interchangeable-block thermal cyclers from Biometra, are manufactured in Gottingen, Germany, where the company claims to be the market leader. The Personal Cycler is designed, as the name implies, for personal use and has the largest capacity "mini-cycler" in the market. It features two interchangeable blocks: one with 48 wells for 0.2 ml tubes, tube strips, or half-sized microtiter plates, and another with 20 wells for 0.5 ml tubes. A four-line LCD display facilitates programming and shows all of the important parameters during a run. The instrument's memory stores 100 programs, each consisting of up to 99 steps. Each step can be repeated up to 99 times. Biometra manufactures the Personal Cycler with an optional heated lid for oil-free PCR. The UNO-Thermoblock accepts one of three interchangeable blocks, accommodating 96 x 0.2 ml tubes or one 96-well plate, 40 x 0.5 ml tubes, and four microscope slides. Equipped with Peltier technology, the UNO-Thermoblock's heating rates can be adjusted from 0.01° to 1.5°C per second for slow cooling or heating for specific applications. Time extension, temperature increment, and pause are some of the programming functions built into the UNO which also stores 30 twelve-step programs. Like the Personal Cycler, each step can be repeated 99 times. The UNO is also available with or without a heated lid. Biometra's UNO II Thermocycler incorporates some unique thermocycler technology. Built around eye-catching silver sample blocks covered with a thin layer of gold to prevent corrosion, the UNO II boasts ramping rates approaching 4°C per second and has a maximum temperature difference across the block of less than 1°C. The excellent thermal conductance of silver also provides for more uniform ramping rates throughout a cycling program when compared to other thermal cyclers. Additionally, the UNO II's integral heated lid applies a defined, optimized downward pressure on tubes and plates. This pressure of 3.4 kg sets automatically to guarantee safe sealing for oil-free PCR and to prevent evaporation. Four interchangeable blocks fit into the UNO II. These hold 48 x 0.5 ml tubes, 96 x 0.2 ml tubes or a single 96-well plate, a 384-well plate, and four microscope slides. Hybaid's PCR Express HybaidPCR Sprint™PCR Express™ Hybaid's PCR Sprint™, the company's newest instrument, has been designed for personal thermal cycling of up to 24 samples. Possessing the smallest footprint in the profile, the PCR Sprint's two interchangeable blocks run 20 x 0.5 ml tubes and 25 x 0.2 ml tubes, respectively. Block exchange is a simple, tool-free procedure, and the standard heated lid affords oil-free operation. A robust Peltier heating and cooling system onboard the Sprint provides heating rates up to 3°C per second and cooling rates as high as 2°C per second. An in-tube thermistor functions as an active tube control system for absolute temperature accuracy. Programming the PCR Sprint consists of simple, alphanumeric procedures with an intuitive user interface and memory for 60 programs. Perhaps the sleekest-looking thermal cycler around, Hybaid's PCR Express™ drives a complement of four interchangeable blocks. These cycle 48 x 0.5 ml tubes and 96 x 0.3 ml tubes, 96 x 0.2 ml tubes or one 96-well plate, four microscope slides with a standard humidity chamber, and one 384-well plate. Its heated lid with auto-adjust single-action closure feature allows oil-free thermal cycling with tubes and plates from any manufacturer. The PCR Express also features intuitive software with alphanumeric programming and memory storage for 99 programs. These can be filed in six user-defined directories. Software upgrades are available from Hybaid's internet site. The PCR Sprint and PCR Express feature a run "end time" calculation function and time and temperature increment/decrement abilities. These instruments also have received "Authorized for PCR" status under an agreement between Hybaid and Perkin-Elmer Corporation. Labline's Programmable Thermal Blok Lab-Line Instruments, Inc.Programmable Thermal Blok Lab-Line's modular Programmable Thermal Blok drives one of a set of four interchangeable sample modules. These handle 60 x 0.5 ml tubes, 96 x 0.2 ml tubes or one 96-well plate, a combination of 48 x 0.2 ml tubes and 30 x 0.5 ml tubes, or four glass slides on the in situ module. Module changes are fast and easy with the removal of four screws and a plug. Two efficient Peltier heat pumps incorporated into each module provide the uniform heating and cooling necessary for thermal cycling across the 0° to 105°C temperature range. In combination with the aluminum alloy composition of the modules, the Peltier system provides controlled ramp rates up to 3°C per second for cycling speed and uniformity. Additionally, all of the Programmable Thermal Blok's thermal elements are rated for 210°C for product durability and safety in the event of accidental overheating. According to Lab-Line, this rating is the highest currently available. PC-based software, with self-diagnostics, is a standard feature of the Thermal Blok. Programming is user friendly, easy to learn, and facilitated by a large keypad and LCD display screen. Lastly, each unit features a standard adjustable lock-down heated lid. MJ Research's PTC-225 DNA Engine Tetrad MJ ResearchPTC-150 and PTC-150HB MiniCycler™PTC-200 DNA Engine™PTC-225 DNA Engine Tetrad™ Recognized as the leader in Peltier-based thermal cycler technology, MJ Research brings three interchangeable block machines to the marketplace. The first, the PTC-150 MiniCycler, is portrayed as the standard personal thermal cycler to which all others are compared. Indeed, this rugged machine has found such diverse applications as identifying whale meat taken from endangered species to tracking the Ebola virus and dengue fever in a mobile molecular lab. Three interchangeable blocks are available for the PTC-150 machines, although they have been designed for only occasional changes. These blocks handle 16 x 0.5 ml tubes, 25 x 0.2 ml tubes, and 36 positive-displacement pipet tips. Holding 25 µl samples, the positive displacement tips enable oil-free PCR and have strong applications for field use. Driven by a sophisticated Peltier-Joule heat pump, the PTC-150 operates across a thermal range of -9° to 105°C and has temperature ramping rates of up to 2.4°C per second. It also features a large memory for storage of up to 80 programs and "amiable" software with a 32-character LCD display. The PTC-150HB version of the MiniCycler features the Hot Bonnet™ heated lid. This lid uses clamp-arm action to tightly seal reaction vessels for oil-free PCR. The flagship instrument of MJ Research, the PTC-200 DNA Engine, is the second member of this family of interchangeable-block thermal cyclers. Designed to accommodate an armada of eight interchangeable Alpha™ module sample-block/heat-pump assemblies, the DNA Engine is the most versatile of the interchangeable-block cyclers in the profile. These eight Alpha modules consist of a combination of single- and dual-block formats. The single-block Alpha modules handle 60 x 0.5 ml tubes, 96 x 0.2 ml tubes or a 96-well V-bottom plate, a 192-well plate, and a 384-well plate. Capable of running two different protocols simultaneously, the dual-block Alpha modules all feature two independently operated blocks in these configurations: 30/30 x 0.5 ml tubes, 48/48 x 0.2 ml tubes, 30/48 x 0.5 and 0.2 ml tubes, and 16/16 glass slides for in situ PCR. All eight modules can be changed in 10 seconds. The list of features for the DNA Engine is impressive and includes a unique Peltier-Joule heat pump, ramp rates of up to 3.0°C per second, the Hot Bonnet heated lid, and a large memory for up to 200 programs organized in 12 named folders. Optional features, such as the motorized Power Bonnet™ lid and the Remote Alpha Dock System which allows an Alpha module to operate in tight quarters away from the base unit, facilitate robotic applications for the DNA Engine. The PTC-225 DNA Engine Tetrad™ is the third instrument in the MJ Research family of interchangeable-block cyclers. Fully compatible with the PTC-200 DNA Engine, the Tetrad runs the same Alpha modules but handles four at once in a base unit that has only twice the footprint of the PTC-200. Overall, the Tetrad runs any mixture of Alpha modules, so that one machine operates four to eight independent blocks with a mixture of sample vessels and a total capacity as high as 1,536 simultaneous reactions. PE Applied Biosystems' GeneAmp PCR 9700 PE Applied BiosystemsGeneAmp PCR System 9700 Originally introduced in 1997 with a 96-well sample block, the GeneAmp PCR System 9700 was designed with the future in mind. Built around a wafer-thin Peltier heating and cooling system that allowed the development of a low-weight, small-footprint machine, the 9700 has been primed for the introduction of new sample block formats. For instance, the recently introduced dual 384-well interchangeable-block format increased the 9700's capacity eight times within the same instrument footprint. Running a total of 768 samples, the dual 384-well block format provides the high sample throughput needed for automated DNA sequencing. While only two blocks are currently available for the 9700, new ones will be introduced as they are conceived and developed. Programming features on the 9700 include many of the intuitive programming methods found on the GeneAmp PCR System 2400. The new back-lit display on the 9700 offers improved viewing of the graphical display, which shows time and temperature profiles of each protocol. In the 9600 emulation mode, users can transfer methods created on the 2400 and 9600 thermal cyclers to the 9700 system without making any modifications. Additionally, the new Max Mode allows users to exploit faster ramp rates, larger reaction volumes, and shorter run times. The GeneAmp PCR System 9700 has received "Authorized for PCR" status. St. John's BioOven III St. John AssociatesBioOven III Employing electrically heated air to heat its samples, the unique BioOven III is this profile's hands-down leader in thermal cycler sample capacity, deftly handling ten 864-well plates. In fact, the BioOven III features an array of interchangeable sample carousels that handle several sample formats, including 0.5 ml tubes; 2.0 ml tubes; 96-, 384-, and 864-well plates; 20 or 30 glass slides; and hundreds of glass capillaries. These carousels accommodate 4, 6, or 10 plates and up to 236 tubes. In addition, custom carousels are available. All of the carousels rotate within the fan-circulated air oven environment contained inside the large chamber of the BioOven III, thereby exposing all samples to the same thermal conditions and high temperature uniformity. Because the entire sample vessel is exposed to heating and cooling, refluxing is not a problem. The BioOven III uses temperature probes that precisely match the sample environment so that the displayed temperature, which drives the controller, accurately matches that of the sample. Its menu-driven controller stores up to 99 programs and features flexible programming and the convenient format function. Here, the user indicates the type of sample format in use, and the BioOven III then optimizes the run specifically for that format. Stratagene's RoboCycler Infinity StratageneRoboCycler Infinity Stratagene's family of RoboCycler Temperature Cyclers tackles thermal cycling by mechanically moving the samples from one heated block to another, rather than ramping a single block's temperature up and down. By incorporating large, isothermic, heat-retaining sample blocks into the works, the RoboCyclers maintain an adjacent well-to-well temperature uniformity of ±0.1°C, the best block temperature uniformity in the industry. According to Stratagene, this block uniformity has important applications for more sophisticated thermal cycling techniques, such as RT PCR, site mutagenesis, and PCR using genomic DNA templates. In addition, the elimination of the need to ramp a sample block up or down to the next temperature reduces the RoboCycler's total cycling times by 30 percent. The standard RoboCycler uses a set of four blocks. Three heated blocks are maintained at the annealing, extension, and denaturization temperatures, and a fourth block is refrigerated for sample storage at the completion of a run. Stratagene's interchangeable-block RoboCycler, the RoboCycler Infinity, features three sets of interchangeable blocks. These contain 40, 96, and 384 wells for 0.5 ml tubes; 0.2 ml tubes or a 96-well plate; and a specially machined 384-well plate, respectively. Each block module is self-contained and easily changed by simply unplugging it and removing the paddle assembly. All three sets are sold with a standard sample paddle, the portion of the robotic arm that physically moves the samples from block to block. For oil-free PCR, an independent Hot Top assembly for each block format is sold separately. Finally, for in situ PCR applications, an in situ PCR adapter accommodating three slides is available for the 40-well blocks. The RoboCycler Infinity is an "Authorized Thermal Cycler" under an agreement between Stratagene and Perkin-Elmer Corporation. Techne's Progene Genius TechneProgene Genius Founded in 1948 as a manufacturer of temperature-controlled products, Techne offers two thermal cyclers with interchangeable blocks. The first, the personal-sized Progene Thermal Cycler, is billed as the smallest, least expensive, and fastest microtube thermal cycler in the world. Indeed, the Progene has the lowest price in the profile and boasts heating and cooling rates of 2.8° and 2.2°C per second in the 55° to 90°C range. The Progene uses advanced Peltier technology to generate its rapid heating and cooling rates and to provide a block uniformity of ±0.3°C. Its two interchangeable blocks accommodate 25 x 0.2 ml tubes or a 5 x 5-microwell plate, and 20 x 0.5 ml tubes. Only four screws need removing when exchanging blocks. A heated lid for oil-free PCR is standard. Techne's Genius Thermal Cycler has been designed for labs with high sample throughput requirements. The Genius handles a 384-well plate, a 192-well plate, a 96 x 0.2 ml V bottom plate, and four slides from its battery of four interchangeable-blocks. Its user-friendly block interchange systems allows block exchange without the use of tools. Additionally, the standard heated lid contains a unique spring device that self-adjusts to fit the different tube sizes used in the various block options. Techne's GENSOFT software is also available as an accessory for connecting the Genius to a computer. This software allows networking of up to 32 thermal cyclers and interfacing with robotic systems. Both the Progene and Genius machines are fully programmable and incorporate Techne's incremental/decremental hold time and incremental/decremental temperature features. The incremental/decremental hold time has applications for incrementally increasing extension times with each cycle for techniques such as Long PCR and RAPD. Similarly, denaturation times may be decrementally shortened with each cycle to maintain the polymerase's half-life. Useful for optimizing annealing conditions, the incremental/decremental temperature feature has applications with Touchdown PCR, among other techniques. Chemical Company in Irvine, California. He can be reached at mdbrush@compuserve.com. Comparison Table

Up On Blocks: A Profile Of Thermal Cyclers With Interchangeable Blocks

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