Pipette History 4

There are many other elements to a mechanical pipette that have improved its safety and usefulness. They may not seem obvious at first glance, but are compulsory on any unit. Imagine a pipette without a tip ejector for example or a tip cone that didn’t seal with a large range of manufacturers tips!  There are countless patent applications and patents granted for these pipette functions. There are many patents that are less obvious, such as those related to reduction of “hand warming” effects (Suovaniemi 1975), or the mechanisms to reduce thumb and tip ejection pressures through use of springs and leverage systems. An example of this is a Beckman application for an “Armed Tip Ejection” mechanism from 1981 or the replaceable tip assembly from Rainin Instruments in 1985.
Pipettes are simply devices to transfer precise amounts of fluid from place to another. Initially it was sufficient to have single tip cone designs with fixed volumes. As time moved on it made sense to have a single use instrument for varying volumes which reduced the need for many fixed volumes. The entire picture changed dramatically in the late 1970’s and early 1980’s however as the use of microplates and ELISA technology developed rapidly with the need for automation and increased sample processing and speed of test reaction times.

Pipette History
The earliest microplate was created in 1951 by a Hungarian, Dr. G. Takatsky, who machined 6 rows of 12 "wells" in a Lucite (a synthetic polymer). By the late 1950’s however a moulded 8 x 12 version had been introduced and the format was seen as a good alternative for performing many types of tests such as haemagglutination.  By the 90’s there were more than a dozen companies producing a wide range of microplates with different features, such as flat or round bottoms or for luminescence or fluorescence use.  There are hundreds of millions of microplates used yearly still, although many of the ELISA technologies have now moved over to dedicated instruments.

Pipete History
The convergence of microplates and pipettes took effect when ELISA technology started replacing radioimmunoassay and the production of ELISA kits for many diseases accelerated using the microplate as the test medium of choice. The ELISA techniques published (in 1971 Peter Perlmann and Eva Engvall at Stockholm University in Sweden, and Anton Schuurs and Bauke van Weemen in The Netherlands) were widely adopted and as the patent record shows pipettes developed accordingly.
In January 1973, the first multichannel pipette patent was filed by Suovaniemi (Pat No: 3,855,658) and was developed into the incredibly successful “Finnpipette Multichannel” manufactured by Labsystems and marketed by Flow Laboratories under the brand name “Titertek”.  The multichannel range included 4, 8 and 12 channels up to 300ul per channel in volume. This product along with the development of vertical light photometry from the same stable launched an industry enabling fast and accurate processing of medical samples in volume.  This invention and the massive increase of microplates spawned many other multichannel pipettes over the years, all having the same commonality of design due to the microplate well spacing. Research into drug development and other screening techniques has changed the market structure and increased the pipette range to encompass 16 channel models for 384 well plates now.
Advances in moulding technologies and plastics allowed further biological advances in cell culture and research applications. This combined with varying microplate formats opened up avenues for variable spacing multi-channels as patented by Matrix Inc. in 1989.  
Pipettes are used for countless applications and manufacturers are always looking for ways to provide tools to make tasks easier and less repetitive.  Movement of fluid from one vessel to another becomes more tiring, cumbersome and increases inaccuracy when undertaken repeatedly. Multi-dispensing devices were recognised as a potential tool and several patents have been lodged for mechanical devices, such as that by Oxford Laboratories in 1976.  
Pipetting like all industries moves with the times and needs to address problems in the workplace both in terms of economy, safety and productivity. For pipetting, developments in the microchip world and advances in battery capacity presented opportunities to rectify known issues:
--Repetitive tasks can lead to the now well know “Repetitive Strain Injury” particularly carpal tunnel syndrome and a loss of dispensing accuracy.
  • --Tip ejection is also associated with RSI. This and thumb plunger pressure are the two main causes of this injury and therefore reducing these forces is paramount.
  • --Speed and accuracy of dispense go hand in hand. The need to accurately fill a complete microplate or tube array quickly for example.
Electronic” or Motorised pipettes have long been in the planning, only held back by technology. The history of who was first and what technology is used can be seen through the Patent history. There are however 4 types of “electronic” pipette;
  • --The Pipetting Aid, a ubiquitous and quite primitive (electronically) tool used in cell culture work.  These are not true pipettes in the accuracy sense of the word
  • --The Stepper Motor Electronic Pipette as introduced by Rainin as the EDP units. Rainin filed a Patent in 1984 for this type of unit.
  • --The DC Motor unit as introduced in 1989 by Biohit, now the World’s most successful electronic pipette sales company, who originally manufactured the “Eppendorf Response” models.
  • --The Hybrid pipette. This is pipette with a digital display but the piston movement is still thumb activated. Rainin filed a patent in 2000 for this type of unit. Also filed (slightly earlier in 1989 by Labsystems is a similar concept).
The barriers to entry are far higher for electronic motorised devices due to the levels of investment in research, development and manufacture. The complex nature of these devices has ensured that the players are only those companies with the technical skills and distribution infrastructure to support such an enterprise. Without doubt Biohit Oyj of Finland dominates the global electronic pipette market, with Eppendorf and Rainin following.  As these barriers to entry have dropped and company mergers and take-overs resulted in start-ups, so have the number of electronic pipette suppliers increased.
Electronic pipetting is now well accepted and the current models will morph into ubiquitous tools of the future. Any concerns over RSI can be put at rest with motorised tip eject and plunger movements, tip fits are guaranteed through spring loaded tip secure mechanisms (such as “OptiLoad”). Multi dispensing, mixing and diluting can all be performed with one pipette.
With all these problems solved and the bureaucrats satisfied you may think the whole world will gravitate to electronic or motorised hybrid pipettes. This will happen slowly as the products do tend to be more expensive and often pipettes may only be used sporadically or may be used in field locations where recharging may not be possible. Third world countries have taken up the manufacturing mantle either themselves or through overseas subsidiaries and have followed the injection moulding, eco friendly route where less material is used in manufacture and less fuel is needed for transport. These products are sold in large volume domestically and are now creeping into the main distribution channels globally. Quality often remains a problem and the manufacturing numbers will shrink as distribution gains even more momentum with changes in brand loyalty and customer perceptions.
There is a problem here however and it is very apparent but seldom considered!  A pipette is only part of the solution. The pipette tip is just as important to accuracy and precision as is the pipette!
There are many more manufacturers of tips than pipettes and the market is of considerable size globally! The history of the pipette tip is our next venture!
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