30 Years of Thermal Cycler Innovations #1: The World’s First Thermal Cycler and How it Advanced Science

By Kenneth Tan, Senior Product Manager, Molecular Biology

The polymerase chain reaction (PCR) is a revolutionary laboratory technique used in molecular biology research worldwide. PCR technology was developed by Kary Mullis at the Cetus Corporation in 1983. Initially, the PCR reaction was a very time-consuming process.  Early adopters had to perform all of the necessary PCR steps manually. Many of these steps required moving the DNA sample back and forth between three large water baths of different temperatures. The invention of an all-in-one machine (thermal cycler) that would help automate the PCR process changed history for molecular biology researchers.

Several key innovations in the mid 1980s led to the development of the first commercial thermal cycler, the TC1 DNA Thermal Cycler (TC1) in 1987.

• One of the first thermal cycler innovations was to automate the transfer of DNA samples between the different temperatures.
• An instrument that facilitated the manual addition of the PCR enzyme was also a key development. When PCR was first conducted in the laboratory, PCR enzymes were not heat-stable; therefore, they had to be added during each cycle manually.
• Most importantly, the key engineering innovation for the thermal cycler was the ability to heat and cool samples using a metal block to adjust the sample to a precise temperature accurately, along with the ability to program the instrument to cycle through these temperatures.

The cooling system of the TC1 thermal cycler was comprised of a refrigerator compressor, and included plumbing within the aluminum sample block. Early-stage heater elements were used. A block temperature control algorithm was developed to achieve accurate and precise block temperatures for successful PCR reactions. Developing an accurate, programmable block hinged on several key criteria:

• A cooling system small enough to fit on a laboratory bench
• Reliability in a wide variety of operating conditions
• Portability

The innovations that inspired and made the TC1 possible paved the way for discoveries that have changed science, including:

– In 1988, R. Saiki and K. Mullis¹ were the first to describe the use of a thermostable DNA polymerase from the bacterium Thermus aquaticus (Taq), using the TC1. And we know how that story evolved: Taq DNA Polymerase revolutionized molecular biology and the analysis of DNA, and it was essential for the development of modern thermal cyclers.

– In 1989, DNA was amplified from the remains of ancient human bones using the TC1², launching ancient DNA research on human populations. This has broadened our understanding of human evolution, of extinct human ancestors, and of the evolutionary history of human disease.

Learn more at thermofisher.com/30yearsofinnovation

 

For Research Use Only. Not for use in diagnostic procedures.

¹ Saiki RK, Gelfand DH, Stoffel S, Scharf SJ, Higuchi R, Horn GT, Mullis KB, Erlich HA (1988) Primer-Directed Enzymatic Amplification of DNA with a Thermostable DNA Polymerase. Science 239:487–491.

² Hagelberg E, Sykes B, Hedges R (1989) Ancient bone DNA amplified. Nature 342:485.

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Kenneth Tan Sr. Product Manager, Thermo Fisher Scientific

Kenneth has 20 years of experience with PCR-related products. He began his career as a project engineer responsible for thermal cycler technology transfer to manufacturing. He moved into the development of thermal cyclers as an R&D system engineer, and then managed PCR and qPCR thermal cycler programs. Currently, he is a thermal cycler and PCR plastics product manager.

Kenneth holds patents related to Applied Biosystems™ VeriFlex™ temperature control technology, and patents related to thermal cycler temperature uniformity.