The Competition Heats Up: The annual review of thermal cyclers takes a sneak peak at the new products for 1999

Date: December 7, 1998Thermal Blocks Table As a strong contingent of companies maneuvers to establish dominance over a diminishing share of the market for thermal cyclers, the pressure to lower costs and develop new technologies has made this a dynamic year for the industry. Frustrated by competition, some companies that have been steadfast promoters of the technology are bowing gracefully out of the industry. However, as the leviathans of the thermal cycler business put pressure on the little guys, a courageous few are beginning to emerge with instruments that are surprising in their originality. Cepheid SmartCycler Cepheid is developing a thermal cycler that is targeted for sale the summer of 1999. The SmartCycler is the brainchild of Alan Northrop, whose research for Lawrence Livermore Laboratories addressed issues relevant to biological warfare. Rapid PCR, real-time optical detection, and independent reaction sites are crucial to identifying potentially harmful bacteriological weapons. Cepheid incorporates each of these functions, including four different fluorescent dyes for monitoring reactions and quantifying DNA products within the sample tube. "The advantage of our system is that it actually presents information in real time," said Northrop, which eliminates the need for electrophoresis. The SmartCycler appears to be positioned to compete directly with Roche Molecular Biochemical's Light-Cycler and Perkin-Elmer's PCR System 7700. Cepheid plans to lure customers with the juxtaposition of high-speed cycling and low cost. Snark Technologies Snark 96 Snark Technologies' year-end release of the Snark 64 and Snark 96 adds two competitively priced machines to a market that has seen many of its lower cost machines withdrawn from service. "Low cost is our primary emphasis; $3,495 is the lowest cost of a fully featured thermal cycler," said Tom Davidson, product manager for Snark Technologies. Davidson said that he and his colleagues looked at the market and thought it wasn't very competitive on price. Believing that the technology had stabilized, they decided to introduce low-cost manufacturing methods to the production of thermal cyclers. The emergence of the Cepheid and Snark thermal cyclers symbolizes the current schism throughout the industry. In order to survive, companies are choosing one of two paths. One segment of the industry is promoting advanced systems with real-time quantification and extremely high throughput. The other segment is trying to maintain a hold on its market share by simplifying function and reducing cost. The result is a variety of products that have benefits for a number of different applications. Although this is a broad generalization, the way the market has been divided traditionally is that academics get the least expensive equipment with simpler programs for training students, whereas commercial interests such as pharmaceutical companies purchase the high-throughput systems and hire a paid technician to keep them running around the clock. Companies such as Bio-Rad, Genex, and Intelligent Automation Systems try to keep as much distance between themselves and their competition as possible so they're not cross-competing for each others customers. The way they have done this is by clearly delineating their respective spheres of operation within the market. BioRad GeneCycler Bio-Rad's Gene Cycler is a modestly priced device that is designed for researchers looking for a personal thermal cycler as well as those in teaching laboratories at the high school and undergraduate levels. Instead of competing with the rest of the industry, which has tended to concentrate its efforts on servicing high-throughput applications, Bio-Rad has carved out a niche for itself in teaching laboratories, where its machines are used to explain the fundamentals of molecular biology to aspiring young scientists. In order to keep costs low and functions uncomplicated so that students may have direct access to the machines, Bio-Rad has kept the Gene Cycler's design simple and easy-to-use. The system features a small footprint, a heated lid for oil free operation, and an in-sample temperature function that reduces concerns about differences in the heating block and the sample. Similar to Bio-Rad's strategy for targeting small research labs or academic teaching facilities, Genex has come forward with a low cost, easy-to-use thermal cycler called The Pacer. Genex has managed to keep the Pacer simple by making it PC compatible. Instead of packing the machine with microprocessors, the Pacer connects to a PC. The PRECEPTOR CD-ROM software enables a desktop computer to function as the brains of the thermal cycler which, in addition to simplifying its appearance, reduces its size, leaving more room on the counter for work space. Intelligent Automation Systems' TC 1600 Intelligent Automation Systems has taken a different approach to thermal cyclers. Instead of creating small-scale thermal cyclers with the individual researcher in mind, IAS has developed a 16-block machine called the TC 1600 with a view to sustaining large-scale, high-throughput industrial use. "Think of it as a production system," said Jose Valle, product manager for IAS. The 16-block behemoth can operate five times a day, seven days a week. Not only do multiple blocks make the instrument capable of processing large numbers of samples, but the cost per block is relatively low. Another hot issue in the world of thermal cyclers is measuring temperatures. With well blocks containing as many as 1,536 wells, it is extremely important to maintain a consistent temperature throughout the entire sample block so that every vial receives the identical amount of heating and cooling. In order to achieve more precise measurements of sample temperatures some manufacturers place temperature sensors within "dummy" wells. One company that has historically provided this feature is Hybaid. Hybaid - PCR Sprint Hybaid, known for its PCR Sprint and PCR Express thermal cyclers, has recently launched a gradient block thermal cycler. The gradient block can be fitted to the PCR Express unit and has the capacity to perform gradient as well as standard cycling. Hybaid's main concern in PCR technology is temperature uniformity. They claim to be the only company that makes built-in tube thermistors to measure true sample temperature. Typically, when setting up gradient protocols dwell time variations exist between annealing temperatures. Hybaid has addressed this through software and its Active Tube temperature control system to accurately monitor sample temperatures. This is to ensure that annealing temperatures are achieved to within 0.5°C. The science of materials is always an interesting topic in any discussion of technology. Whether the subject is synthetic polymers, silicates, or Bucky balls, there is seemingly no end to the variety of molecules that can be applied to any given problem. When engineers run out of ideas or encounter serious obstacles for improving the mechanical workings of a particular design, they frequently look at the materials they're working with to see if they can be altered to improve an existing product. Manufacturers of thermal cyclers have experimented with different metals to improve the effectiveness of their products. Although most blocks are made from aluminum coated by a hard-anodized surface of corundum crystals, some manufacturers are turning to silver-gold blocks for their accelerated ramping rates. Biometra and Stratagene are just two of the companies that have made the move from aluminum to silver-plated gold and nickel-plated copper. Biometra launched the Tgradient thermocycler on November 12th. It is the culmination of 9 years in manufacturing thermal cyclers. This is the first gradient cycler based on the technology of its TGGE system. In addition to silver blocks with a 4° C/sec ramping rate, the instrument will support a 40° C gradient and have user-interchangeable blocks for 96x0.2ml, 48x0.5ml and 1x384 mtp. Tony Sanchez, product manager for LabRepNet (Biometra's US distributor) said, "Biometra has been making thermocyclers for nearly 10 years and has learned a great deal about what to do and what no to do when making a peltier-based unit." Stratagene RoboCycler® While other manufacturers of thermal cyclers are attempting to achieve faster ramping rates by using specialized materials, Stratagene has developed the RoboCycler temperature cyclers, including the RoboCycler Gradient 96 and 40 temperature cyclers, that use a robotic arm to move samples between isothermally uniform blocks. "Many researchers blame their template or primers when their PCR is not successful. They do not consider how the design of the cycler can affect the PCR thermodynamics," said Brent Keller, product manager for Stratagene. Stratagene has conducted extensive testing on temperature uniformity between well and across the block of several cycler models. Keller, who is critical of the efficiency of Peltier heating devices, argues that Peltier systems are designed to cycle quickly, but not uniformly. "PCR conditions must be uniform, both within the tube and between the sample tube," commented Keller. Therein lies the rub. Keller believes that even though Peltier systems may cycle very rapidly, they suffer from temperature uniformity and lag problems. "This can detrimentally affect sensitive genomic or reverse transcriptase PCR amplifications, fluorescent tagged cycle sequencing, and quantitative PCR techniques." Like its progenitors, the new Infinity RoboCycler with interchangeable 384 and 96-well formats is an example of how Stratagene has attempted to combat temperature variation by maintaining a uniformity of ±0.1°C. By introducing both in-point and real-time quantitative PCR analysis, Stratagene's next generation of instruments will permit researchers to measure precisely the amount of product that is in a tube as well as the rate of amplification. As the uses of PCR are expanding, making thermal cyclers more commonplace, manufacturers have begun to identify specific technical challenges that are faced by researchers in their day-to-day work. Automated systems that are capable of rapidly titrating large sample capacities have caused many product managers to sit up and take notice of the creative ways in which some of these instruments are being adapted. Idaho Technology's RapidCycler™ According to Kim Woodhouse, product manager for Idaho Technology 's RapidCycler®, the key to a successful experiment is removing people from the process. An old adage says,"Too many cooks spoil the broth." Only in this particular instance, we might say, "Too many scientists contaminate the reaction." The people at Idaho Technology believe that by reducing human intervention, PCR can run cleaner and faster. The engineers at IT are currently working to develop one-step machines that reduce user interface by cleaning samples and proceeding directly to gels. MJ Research From the time that MJ Research developed its first Peltier cycler 10 years ago, MJ Research has been a major contributor to the cause of thermal cycling. Its sophisticated DNA Engine and Tetrad have made it one of the most recognizable manufacturers of thermal cyclers in the industry. According to vice president of communications John Hansen, MJ Research is interested in automation concerns and ways to more easily integrate its cyclers into current systems. He explained that as well plates approach their maximum density, greater automation is required to process the small sample volumes that becomes a difficult if not impossible task using human fingers. The company is also researching better ways to seal high-density plates and keep them from sticking to blocks. In the final analysis, what all of these technical advances are aiming toward is speed. The goal is to get the most product with as little fuss as possible in the least amount of time. The use of the Peltier system by MJ Research was a major improvement in the speed of thermal cyclers ten years ago. Since then, interchangeable blocks, gradient cyclers, and new heat-resistant polymerase have further increased the speed and productivity of thermal cycling. Many companies have found ingenious ways to enhance existing systems, while others have departed almost entirely from the standard model. Ericomp DeltaCycler Well known for its DeltaCycler and Powerblock systems, Ericomp has responded to the changing demands of its customers by focusing on economical and durable multiblock cyclers. According to product manager Craig Alvis, one reason researchers are using smaller sample amounts, in part, is that the cost of reagents is high. Multiblock Peltier systems that use high-throughput blocks are able to cycle large numbers of samples inexpensively. To further enhance the economy of these instruments, Ericomp is expanding its format to include 384-well plates. Ericomp's cyclers are also distinguished by heated lids that have an added midposition heater, which enables the system to control condensation and low-volume samples. Techne - Robotic Deck Cycler Jennifer Wax, product manager at Techne, said that she was sensitive to the industry's trend toward very high throughput. Higher demands for low volumes of samples has driven the development of interchangeable blocks with increasing well capacity. As the speed and sophistication of these instruments continue to advance, prices have risen accordingly. However, Techne has made an effort to curb the inflationary trend in thermal cyclers. With the introduction of its Robotic Deck Thermal Cycler, which adapts to any existing liquid handling deck, Techne plans to make its devices universally accessible. Eppendorf MasterCycler® gradient Eppendorf Scientific was first to market with a single block gradient thermal cycler, the Mastercycler® Gradient. The Mastercycler Gradient is capable of testing 12 different temperatures simultaneously across a gradient that can be set between 1-20° C. Eppendorf also offers a non-gradient version called the Mastercycler Personal. Both units feature cross-compatible personal memory cards and a universal block that can hold either 0.2ml or 0.5ml tubes and PCR plates. As other companies are beginning to appreciate the advantages of the gradient design, Eppendorf Scientific is looking for ways to break away from the pack. Eppendorf Scientific has introduced a complete line of innovative consumables, a line of Taq Polymerase, and a MasterTaq kit that features a PCR enhancer that the company says gives more reproducible and robust PCR. "It is our goal to be a company that provides, one-stop shopping" for our customers' PCR needs," says Vincent Prezioso, product manager for Eppendorf. "We plan on launching many new instruments and reagents for PCR in the coming year." St. John BioOven III St. John Associates, the 15 year old Beltsville, Maryland instrument maker, recently acquired BioTherm Inc., manufacturer of the BioOven III thermal cycler. The BioOven III provides a unique solution to the conflicting requirements of sample capacity, cycle speed, and type of sample container. Instead of heating and cooling media-specific heavy metal blocks, the BioOven III uses a light-weight rotating carousel that is heated and cooled by circulating air. Tubes, plates, slides, and capillaries all can be accommodated. The BioOven also features a fast-response probe that senses the temperature inside the tube or plate, a feature that is claimed to produce some of the fastest cycle times in the industry. The future of technologically advanced thermal cycling appears to belong to real-time DNA quantitation. Presently, only two instruments are available that have such a capability: the 7700 PCR System from PE Biosystems and the Light Cycler from Roche. Although Cepheid plans to release its SmartCycler in the summer of 1999, until then, these two cyclers own the field. PE Biosystems PCR System 7700 PE Biosystems is the biggest manufacturer of thermal cyclers in the industry. Although it may not be the first company to market with the newest and latest gadgetry, it does provide instruments for PCR that have garnered consumer loyalty. The reliability of PE Biosystems PCR Systems is indicated by the claim that the company hasn't had a Peltier failure since its first Peltier machine was introduced in March of 1997. This record of success should satisfy some critics of Peltier technology. The newest model of PE thermal cyclers incorporates a graphic interface that is claimed to require little or no training, and a guarantee that every instrument will perform up to specifications with a full sample load. PE also claims to have one of the most uniform ramping cycles according to tests conducted with machines working at full burden. The LightCycler, true to its name, is one of the few thermal cyclers that employs fluorescent technology. Using special DNA probes, researchers can now quantify PCR in real time. The primers that are used in the Light Cycler contain fluorophors that fluoresce when activated by light at 470 nm. A built-in fluorimeter detects the fluorescent signal and monitors the rate of the reaction via computer/software interface. Roche LightCycler Rapid cycling is also a feature of the instrument, with a cycling time of 35 cycles in 30 minutes. Steven Bye, a product manager for Roche Molecular Biochemicals, attributes the speed of the system to the use of air as the heating and cooling medium. He suggested that this system is quicker than thermal block designs, which are limited by the conductivity of the block material. Though originally the invention of Idaho Technology, the Light Cycler has been re-engineered and is now manufactured and distributed by Roche Molecular Biochemicals. As for the future of the Light Cycler, Bye assured that the instrument's ongoing development with RT-PCR quantification kits would make it an invaluable asset to researchers working with mRNA. End of the year buying decisions are always difficult. Should you go out and get the brand new 1999 model off the showroom floor, or do you get last year's model for a discount? Some companies that have discontinued their lines of thermal cyclers are selling their remaining inventory at greatly reduced prices. However, the buyer should beware that when the product line has been discontinued, the infrastructure for supporting that machine has also been dismantled. That means no customer support, no spare parts, and no one to fix it when it breaks. Though, if you already have one of the older models in your laboratory it might be a good idea to go ahead and buy one of the discontinued models. That way you can always cannibalize spare parts from the existing machines you already have. It is safe to say that Peltier technology has been well established at this point. As the usefulness of Peltier devices continues to be demonstrated in a growing number of machines, many of the problems that once made Peltier thermal cycling a less than exact science, have been obviated. The advent of interchangeable blocks has also made Peltier machines a preferred method for many researchers. Gradient cyclers have also proven their effectiveness in generating optimal results in PCR and have caught on in rapid-fire succession as companies scramble to add the gradient format to their line of products. The success of new gradient cyclers will, no doubt, have an important influence on which direction the industry decides to take with regard to this technology. Fluorophor, in-the-tube quantification in real time is somewhat of a fledgling science, but it is already showing great potential. As the industry gradually converges on the ideal for thermal cycling, no doubt radical changes in the design of the thermal cycler will become fewer. The thermal cycler, as such, has been characterized to where any major departure from existing formats will be greeted with suspicion. In this respect, the industry is at a crossroads. The success or failure of these competing designs in the ensuing months will largely determine how thermal cyclers are built in the next century. Thermal Blocks Table The author can be reached at bjohnson@the-scientist.com.

The Competition Heats Up: The annual review of thermal cyclers takes a sneak peak at the new products for 1999

Interested in reading more?

Become a Member of