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Friday, August 14, 2015

A trip to the past: Where the hell are the micropipettes??!!!!!!!!!!


Imagine you are taken by Michael J. Fox into a trip to the past and you travel back 50 years. How well do you think you would manage in a lab from the 60’s?Oh wait!! Where the hell are the micropipettes?!!!!!!!

After suffering from tuberculosis as a soldier in the World War II, which probably saved his life, a one of a kind man named Heinrich Schnitger decided to study medicine…but not to practice medicine itself, but as he once said to control his health while protecting himself from incompetent doctors (told you... one of a kind!)

 At the age of 32 he joined the group of Theodor Bücher, Director of the Institute of Physiological Chemistry at the University of Marburg (Germany) as a post-doc. It was a time when pipetting by mouth was still the only method used.  Schnitger was assigned to work with the new anion exchange chromatography, used to measure phosphate-containing metabolites1. A gradient of up to 80% formic acid, following gravity flow, separated nucleotides and other anionic metabolites, which were collected in up to hundreds of fractions, often less than a millilitre in volume, for further analysis. Within a few weeks and to everyone's surprise, Schnitger developed a piston-driven pumping system, which replaced the gravity-driven flow of acid by more exact pump-controlled pressure…. And without any Google search!

While doing his routine work of aliquoting chromatography fractions for further analysis, Schnitger viewed micropipetting by mouth with great contempt. He eventually disappeared from the lab for a couple of days and came back with a self-designed tool to pipette microlitre volumes. Initially, Schnitger 'rebuilt' a tuberculin syringe by adding a spring to the piston that met an upward stop to define the pipetting volume. The syringe needle was replaced by a polyethylene (PE) tip, pulled from PE tubing. An air buffer separated the fluid from the syringe piston and confined it to the plastic tip. The clever features of Schnitger's device dramatically sped up and eased many other experiments as it enabled more accurate pipetting of all aqueous solutions.
And what did his boss do? Well, Bücher soon realized the enormous potential of this invention and as every great boss should do, he encouraged Schnitger to develop the pipette further while relieving him of his research work. Oh yeah!

Schnitger added various mechanical measures required for the exact and repetitive pipetting of small volumes. A major breakthrough was the introduction of a second spring, which allowed the piston to be pushed beyond the delivery point to blow out any residual fluid from the plastic tip.
 Schnitger also profited from the institute's excellent mechanical workshop, which was established by Bücher. On the basis of his prototypes, the workshop technicians produced copies for use in the lab.
Six months after he had built his first prototype, and conscious of its importance,Schnitger applied for a patent in Germany. His application, dated 3 May 1957, entitled “Vorrichtung zum schnellen und exakten Pipettieren kleiner Flüssigkeitsmengen” (Device for the fast and exact pipetting of small liquid volumes), was finally granted on 24 April 1961.

Soon, the medical supply company Eppendorf (Hamburg, Germany) bought the exclusive license for manufacturing and marketing the micropipette. Wilhelm Bergmann was responsible for developing the micropipette. It was further improved and most importantly, the newly available polypropylene (PEP) was used to create the tip which was ideal for single use. As an important addition, Bergmann created the 1.5 ml and 0.75 ml PEP centrifuge cups (the eppendorf tubes or eppitubes) with their snap-on tight cover as convenient vessels for transferring fluid with the micropipette, which quickly impressed laboratories worldwide. A microcentrifuge complemented this new toolset, in which the micropipette was to become an integral part of enzymatic assays together with the Eppendorf photometer. What an amazing combo right?!


Eppendorf failed to conquer this large market by focusing on technical perfection rather than on marketing. Eventually, Gilson Inc. (Middleton, WI, USA) realized its enormous market potential and created its own brand with a variable volume setting.

Schnitger did’t stop inventing, from a novel fraction colector to UV-micro-spectrophotometer with quartz optics to allow meaurements of 10 ul samples.

This man impressed me. I think just the invention of the micropipette would do for an entire PhD thesis. But what amazes me the most is how tiny problems would lead to such great technology improvements. Does any of us take time nowadays to solve problems like that ourselves? I was lucky enough to have my first lab experience in a lab where shelves were filled with hooses, springs and anything you can imagine for a ‘do it yourself’ experience that was encouraged by my mentor Dr Jaime Eyzaguirre Philippi. Though I must confess I wasn’t very good at it.

Anyways, I also love the hi-tech generation, with such incredible technologies such as cell cytometry, Mass- spec., Microscale thermophoresis, among so many others, with such an easy handling and beautiful outcomes, that make our scientific experience so much better.
  1. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1369176/

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