Tech Resources
Necessity is the Mother of Invention
18-Jul-05
Sabine Drecker, BioTek Instruments GmbH
The first microtiter plate was made by hand; liquid handling was performed with knitting needles.
The best ideas are born of necessity. Nobody can say which unexpected inventions may arise from such ideas and which markets they may build. The prototype of microtiter plates was invented more than fifty years ago. Today, microtiter plates and readers are essential equipment in all life sciences laboratories.
The first microtiter plate was hand-made in 1951. A serious influenza epidemic in Hungary urged the physicians to find a fast, economic and reliable test method for the identification on the influenza virus. Standard test methods involving reagent tubes and dilution series were too unreliable and also too tedious, too expensive and time-consuming. In addition, most laboratories lacked equipment and money. However, this was just the right environment for such a revolutionary idea - a common phenomenon in the invention of technical improvements. Therefore, 1951 is the year of birth of microtiter plates.
1951: The Year of the Birth of Microtiter Plates
It was the Hungarian physician, scientist and inventor Dr. Gyula Takátsy who had the idea to place sample tubes on a plate. Using a side-by-side arrangement of wire metering loops, he was able to fill multiple sample tubes with a defined sample volume at the same time, thus significantly increasing the sample throughput of his laboratory.
For time-saving, Dr. Takátsy soon replaced the wire loops by thin iron or steel knitting needles that could be flame-sterilized. He arranged the needles in a way that he could keep them in his hands without problems. This led to a plate with 8 x 12 wells that could be quickly and easily filled - the 96-well plate was born.
Dr. Takátsy improved this method with his “microtitrator“. He evaluated a number of materials and optimized his invention to save even more time during pipetting. However, it took another five years, before his work was internationally accepted. From this time, the triumphant progress of microtiter plates led to its use in different application ranges like clinical diagnostics, molecular biology and cell biology, also in food analysis and pharmaceutics. Without Dr. Takátsy’s invention, recent scientific applications involving high-throughput screening would be impossible.
New Scientific Disciplines
In particular clinical chemistry and of course the immune diagnostics of the late seventies and early eighties had a great demand in convenient and quick solutions for the processing of large sample numbers. Therefore, the technical staff of equipment manufacturers put a large effort into designing more exact, more economic and quick detection methods.
However, titration was still the quantitative detection method involved. It would still take some time until the benefits of photometry would be utilized and even years until the first microtiter plate reader as we know it today would be designed. The great handicap of titration was inherent in the method: in volumetric analyses like titration, the endpoint is defined by a change in color. Therefore, its assessment is often subjective and thus a source of error to be deleted. The technology of choice was photometry, offering the wanted objectivity. However, the requested sample volume was by far too high to be processed by standard photometric measurement. The measuring arrangement of photometers, i.e. light source è filter è sample è detector, does not allow to measure more than nine to ten cuvettes in a sequence. Each sample has to be individually exposed to the light beam.
Vertical instead of Horizontal Measurement
The solution was ingeniously simple. The technicians had the idea to measure the samples with a vertical light beam, making it relatively simple to measure a high number of samples through the sample bottom when closely arranged in a matrix. The consecutive sample measurement could be performed by moving the sample matrix along the detection site or by moving the measuring device from sample to sample. However, classic photometric measurement is based on the Beer-Lambert Law and requires a well-defined sample thickness in the direction of the light path.
While classic photometry solves this problem using cuvettes with defined thickness, vertical photometry involved highly exact dispensing of the sample volume, because the direction of the light path is from the bottom of the sample tube to its meniscus or vice versa. No reliable procedure was available at that time, and some time would pass, until microtiter plates would be used for samples. We should keep in mind that they had not been originally designed for photometric purposes. Plates were filled with pipettes and later with multichannel pipettes; therefore, the matter of reproducible sample thickness was solved.
Today, working with microtiter plates is an essential part of laboratory work in biology, chemistry and biotechnology. Applications range from biochemical, medical and cell-biological methods to the pharmaceutical screening of active compounds. Microtiter plates and their periphery develop independently. Increasing needs in high-sample throughput and low-volume measurement lead to the design of economic, time-saving fully automated equipment with highly sensitive detection devices.
Small Footprint, Flexibility, Precision
In the course of time, microtiter plates underwent many changes and modifications to meet market requirements. Also readers were further developed and optimized for a number of various applications. Today, they are easier to use, smaller and more precise than ever. Also flexibility has become an increasingly important issue. For example, photometers with a monochromator for any wavelength are available, and they are equipped with software that even makes it easy to fulfill FDA requirements like 21 CFR Part 11.
Microtiter plates together with the respective readers and automated devices made life easier for countless users in laboratories. Even today, the handling of high sample numbers would be almost impossible without the equipment that evolved from the pioneering spirit and inventiveness of a man who used a shortage in material to successfully develop an idea. Thank you very much, Dr. Takátsy!
Dr. Gyula Takátsy, 1914–1980, Hungarian physician, researcher and inventor
Still today, Hungarians celebrate “their” Dr. Gyula Takátsy as a man, who has significantly promoted diagnostic methods for influenza virus in the early fifties. However, people more rarely recognize his creativity and inventiveness that invented the microtiter plate and thus launched diagnostics and therapeutic methods into a new era.
In 1955, Dr. Takátsy presented his idea of a 96-well-Platte in the journal Acta Microbiologica et Immunologica Hungarica. Meanwhile, even plates with the hundredfold number of wells are used. Methods like high-throughput screening current diagnostics would be impossible without his ideas.
References
Suovaniemi, O.: “Automated Instrumentation for Clinical and Research Laboratories”, 1998 Helsinki
Takátsy, G.: “The use of spiral loops in serological and virological micro-methods”, 1955 Budapest
Roy L Manns: “Necessity is the Mother of Invention”, PolyPops Development Foundation
