Pipettes no longer suck

Pipettes no longer suck

It’s been 60 years since Eppendorf brought the very first piston-stroke pipette to the global market. What better way to celebrate than to take a delve into the history books and find out where it all began?

Take a look around any research, industry or hospital lab and you’ll be hard pressed not to find a plethora of pipettes. These seemingly innocuous devices grace nearly every benchtop. They are essential to almost all laboratory protocols and serve a paramount importance in modern bioscience and biotechnology. Their necessity has been long-standing in the world of science but if it wasn’t for Eppendorf ushering in the age of precise and accurate pipetting, might we still all be mouth pipetting?

Leaving a bad taste: mouth pipetting

If we take a journey back in time to the 18th century, we can find the earliest pre-cursors to the modern-day pipette; the berthollimêtre and the alcalimetre, developed by French chemist, pharmacist and inventor Francois Descroizilles1. Joseph-Louis Gay Lussac later made some slight modifications to these early designs and coined the term pipette in 18241, however, it wasn’t until the 1950’s that pipettes began to truly resemble those we know today.

Universally considered the original architect of the micropipette, Heinrich Schnitger joined a research team at the Institute of Physiological Chemistry at the University of Marburg in 1957 where he quickly grew frustrated by the inadequacies of mouth-pipetting2; a technique whereby the user would suck up liquids by mouth into thin glass tubes. Not only were these pipettes routinely cleaned with dangerous chemicals such as sulfuric acid, but anecdotal reports linked mouth-pipetting to the ingestion of hazardous substances, including a typhoid culture3 and even plutonium4. Following a very brief disappearance from the lab – merely a few days – Schnitger returned with a self-constructed tool capable of aliquoting microliter volumes.

The tool, now widely termed the “Marburg” pipette, consisted of a repurposed tuberculin syringe, fitted with a spring to the piston that met an upward stop to determine the volume. In addition to substituting the syringe needle for a polyethylene tip, Schnitger engineered the tool such that an air buffer separated the liquid from the syringe piston thereby confining it to the polyethylene tip2.

Schnitger’s role in the story of the micropipette does not end yet. His supervisor at the University of Marburg was quick to realise the significance of Schnitger’s invention and in turn, relieved him of his research duties and encouraged him to pursue work on his innovation. Following the introduction of a second coaxial spring – allowing the user to expel the last drop of liquid – along with some other minor modifications, Schnitger applied for a patent in Germany, dated 3rd May 1957. Nearly four years later, on 24th April 1961, his patent application was finally granted. It not only described all the essential features of the modern pipette but also ideas on how to decrease errors from ambient temperature effects and an outline of the mechanics required for pipetting variable volumes2.

Heinrich Schnitger filed for a patent describing a "device for the fast and exact pipetting of small liquid volumes" - the first micropipette.
The Eppendorf piston-stroke pipette keeps evolving after the launch of the first "Marburg pipette" in 1961.

Eppendorf paves the way for modern liquid handling

Eppendorf was the first to recognize the importance of Schnitger’s invention and their in-house engineer, Wilhelm Bergmann, continued to invest in further development. Amongst Bergmann’s modifications were new shapes for better handling and the replacement of Teflon with polypropylene (PP) for tips. This work culminated in the first commercial piston-stroke pipette, launched by Eppendorf in 1961. Not only did Bergmann play a pivotal role in bringing the piston-stroke pipette to market, but he is also credited with the design of the first successful disposable tube for handling microliter volumes (the “Eppi”).

Technical drawing of the first Eppendorf Tubes® ("Eppi™"). The development of vaccines would be unthinkable today without the Eppi™ and its specific material properties, which Eppendorf has continued to develop.
The Eppendorf "microliter system": the holistic approach set new standards in labs around the world.

Alongside the piston-stroke pipette, the microliter centrifuge and the thermo-mixer, these disposable tubes formed Eppendorf’s microliter system; a revolutionary toolset in many scientific disciplines. Sadly, only a few years after Eppendorf took his invention to market, Schnitger drowned in a Bavarian lake in 19642. However, his legacy and his propensity for innovation lives on through Eppendorf. It continued to invest in the development of the piston-stroke pipette, bringing us the Eppendorf Comforpette 4700 in 1976. The Comforpette 4700 was the first pipette to include automatic tip ejection, eliminating the need for direct contact between the hand and the used tip; an especially important mechanism when working with hazardous liquids.

The first pipette with automatic tip ejection: the Eppendorf Comforpette 4700.

The continued global dissemination of pipettes brought to light new challenges and inspired new designs. For example, the original pipette relied on the air-cushion principle, and although highly accurate for most applications, can be affected by temperature and atmospheric pressure, as well as the viscosity, volatility and surface tension of the solution. Consequently, positive displacement instruments were designed. Unlike air-cushion pipettes, positive displacement instruments do not integrate the piston inside the pipette. Instead, the piston forms part of specialized disposable tips and is in direct contact with the liquid.

The lack of air buffer in positive-displacement pipettes ensures liquid properties do not interfere with accuracy, making them a perfect choice when working with difficult liquids. The Multipette/Combitips® system, first released by Eppendorf in 1978, works according to the positive displacement principle. It was the very first instrument allowing the user to fill the tip once and dispense multiple times – and remains a driver for efficient liquid handling and a staple in many labs working with plates or series of tubes. The current Multipette models are the most important positive displacement pipettes in Eppendorf’s portfolio, retaining the quality of its predecessors while combining the latest innovations in pipette technology.

The Multipette®/Combitips® manual dispenser/tip system quickly enjoyed great popularity in laboratories.

A promising future

An incredible 60 years has passed since Eppendorf launched the very first commercial piston-stroke pipette; a tool that has fundamentally revolutionized science. This pivotal moment means that Eppendorf’s DNA is ingrained in every pipette manufactured since. However, the story does not end here. Eppendorf’s commitment to providing the best liquid handling solutions continues to result in innovative designs that make the lab an ever-more efficient, safer and generally better place to be!

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1. Origins of the Pipette: Why Today’s Scientists Don’t Need to Use Their Mouths – The Incubator. http://incubator.rockefeller.edu/origins-of-the-pipette-why-todays-scientists-dont-need-to-use-their-mouths/.
2. Klingenberg, M. When a common problem meets an ingenious mind. EMBO Reports vol. 6 797–800 (2005).
3. Phillips, G. B. & Bailey, S. P. Hazards of Mouth Pipetting * 1190.
4. Lawrence Bartell’s Interview | Manhattan Project Voices. https://www.manhattanprojectvoices.org/oral-histories/lawrence-bartells-interview.

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