Micropipette – The scientist’s paintbrush

Just as painters would struggle to practise their craft without a paintbrush, scientists and technicians alike would be disorientated without a trusted pipette. Pipettes, especially micropipettes, allow scientists to accurately transfer and measure hazardous or harmful substances which are often less than a millilitre in volume.

A lab, and a scientist for that fact, is simply redundant without one.However, before the invention of the micropipette, measuring small quantities wasn’t so simple, or even safe to do so. So how did the micropipette, a tool used by every calibre of scientist, come to its renowned use?

French pipetting: Pasteur Pipette

The term “pipette” was first coined by the French scientist Joseph-Louis Gay-Lussac in the 1820s. However, Louis Pasteur constructed a version of the pipette still utilised in labs today1. Pasteur, a microbiologist by nature, created a pipette to ensure that foreign contaminants were not introduced into his experiments. This provided a sterile environment where decisive conclusions could be made.

The Pasteur pipette, made from either glass or plastic, is similar to an eyedropper and can even be used to dispense cosmetics. However, within the lab, this pipette is not recommended when accurate volume measurements are required. It is generally utilised to add liquids in a drop-wise manner.

Spit, Not swallow: Carlsberg Pipette

Figure 1 Rebel in a lab-coat: Dr.Adah Elizabeth Verder mouth pipetting an unspecified solution, she studied gastrointestinal flora at the National Institute of Health.

The Carlsberg pipette was constructed from a long, thin graduated piece of glass which allowed air flow but, limited the movement of liquid during pipetting. This was an improvement over the Pasteur pipette as it provided accurate volumetric measurements for scientists to utilise. The Carlsberg pipette required suction to measure and transfer liquids, which only 60 years or so ago, was done by creating a vacuum with the user’s mouth (Figure 1)2.

This type of pipetting was aptly named “mouth-pipetting” as the substance was drawn up by an action similar to sipping a Pepsi by straw. This type of pipetting was not for the faint of heart, as one wrong move could have the user inadvertently swallowing toxic or infectious reagents. Successful pipetting by-mouth required adequate experience by the user and depended on the construction of the Carlsberg pipette.

Unsurprisingly, accidents were so widespread that a review of 57 laboratory accidents which caused 47 infections in staff, found that 40% of those infections were attributed to mouth pipetting3. Such hazards and accidents relating to mouth-pipetting were well known to US Army Biological Labs in 1964 during the introduction of the Carlsberg pipette3. This prompted the use of suction devices. Much like a rebellious teenager who refuses to listen, after the introduction of suction devices, mouth-pipetting was still a widely “acceptable” practise in many labs.

Sick of sucking: Marburg Pipette

Figure 2: Ingenious mind: Heinrich Schnitger revolutionised the pipette into one which is safely and heavily used today

Heinrich Schnitger (Figure 2)4, a son of an inventor, joined the Institute of Physiological Chemistry at the University of Marburg as a postdoctoral student in 1957. There he would go onto to create, using the institutes workshop, the micropipette scientists recognise and utilise today.

His post-doctoral studies involved exchange chromatography experiments that separated substances based on their charges. However, during his experiments he found the chromatography methods produced samples that were less than a millimetre in volume. A close witness to Schnitgers work at the time, Martin Klingenberg, outlined that when collecting the fractions, Schintiger “viewed micro-pipetting by mouth with great contempt4.”

His annoyance towards mouth-pipetting grew to such a level, like a modern-day messiah, he disappeared from the lab for a couple of days. Upon divine reappearance, he returned with a tool to pipette microlitre volumes

Astonishingly, his prototype of the micropipette had many features of what a modern micropipette looks like today (Figure 3)5,6 which consists of a spring-loaded piston and a removable plastic tip7. The plastic tip is thrown away after every use to ensure no cross-contamination takes place between reagents.

Figure 3 : Relic of the past, modernised: (left) shows the initial micropipette developed by Schnitger and (right) shows a modern micropipette produced by Eppendorf which has many common features of the original design.

Understanding the importance of the breakthrough, copies of the pipette were made throughout the institute for use. Feedback from scientists using the pipettes were taken into account to improve and alter the initial design. In the same year, the prototype was created, Schiniger applied for a patent in Germany, which was swiftly accepted in 1961.

World-Market domination

Figure 4: Commercialised success : Shows the patent application submitted by Schnitger which was shortly bought by Eppendorf for widespread commercial production.

The real test of the usefulness of his invention, was whether it came to widespread use to avoid the hazards associated with mouth-pipetting. To appeal to the general and wider scale market, Wilhelm Bergman used different shapes and materials to further optimise the micropipette. Shortly afterwards, Eppendorf, a supplier of lab equipment, bought the intellectual rights to manufacturing and marketing the micropipette (Figure 4)4. The initial launch of the pipette, dubbed the Marburg pipette, was widely accepted and used throughout Europe and Germany.

According to one source4, the use of the micropipette didn’t quite catch on in the US as Eppendorf was focusing more on optimisation rather than advertisement. An American company, Gilson, marketed the same pipette, with the addition of an adjustable volume capacity, through the exploitation of various loopholes in patent law. The marketing of the Marburg pipette was a success, and mouth pipetting fell out of fashion and mostly became the subject of edgy jokes between many scientists today.

Sadly, Schnitger died before the global spread of his invention due to a swimming accident in 1964. To an extent, he knew the importance of his work, but there is a difference between knowing and seeing your inventions used, even decades later, throughout the world by scientists and students alike.

Innovation,the cornerstone of science

The Pasteur, Carlsberg and finally the Marburg pipette present the innovative and collaborative nature of science. Each iteration of the pipette has somewhat built upon the previous version. However, there is an astounding feat of difference between the Carlsberg and Marburg pipette that Schnitger achieved which deserves honourable mention.

Modifications and improvements of the Marburg pipette are taking place even today, to produce more ergonomic designs, presenting the never-ending quest to optimise tools for research and teaching uses.

References:

1.         Joseph-Louis Gay-Lussac | French scientist. Encyclopedia Britannica https://www.britannica.com/biography/Joseph-Louis-Gay-Lussac.

2.         Dr. Adah Elizabeth Verder mouth pipetting. (2017).

3.         Phillips, G. B. & Bailey, S. P. HAZARDS OF MOUTH PIPETTING: http://www.dtic.mil/docs/citations/AD0640356 (1964) doi:10.21236/AD0640356.

4.         Klingenberg, M. When a common problem meets an ingenious mind. EMBO Rep. 6, 797–800 (2005).

5.         Martin Klingenberg. The Original Micropipette. The Scientist Magazine® https://www.the-scientist.com/foundations-old/the-original-micropipette-48026.

6.         Pipette.com. Eppendorf Pipettes | Manual/Electronic Pipettes, Repeaters, Dispensers. https://www.pipette.com/Eppendorf-Research-Plus-Fixed-Volume-Pipette.

7.         Vellayutham, B. Who invented pipette? | The Petri Dish. https://thepetridish.my/2019/06/30/who-invented-pipette/.

Photo credits:

Pipette Icons made by Freepik from www.flaticon.com

Micro-pipette photo by Polina Tankilevitch from Pexels

Pasteur-pipette photo by Edward Jenner from Pexels

Lab-bench top photo by Polina Tankilevitch from Pexels

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