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Evolution of Biological Shakers and Stirrers

Mixing solutions is one of the most common laboratory tasks. Over the years, a number of automated methods for mixing have been devised, all of which remove this burden from the operator by offering a sustained and controlled stirring action for indefinite periods of time.

by John Buie

Mixing solutions is one of the most common laboratory tasks. Over the years, a number of automated methods for mixing have been devised, all of which remove this burden from the operator by offering a sustained and controlled stirring action for indefinite periods of time.

Magnetic stirrers are a popular type of laboratory stirrer that use a rotating magnetic field to cause a stirrer bar to rotate within the solution. These stirrers are often combined with a hotplate and are ideal for small volumes of non-viscous liquids and for situations in which a reaction must take place in a closed vessel or system. The overhead stirrer, however, is more suitable for larger volumes and more viscous solutions, but can be less convenient and more time-consuming to set up.

Laboratory shakers consist of an oscillating board on which solutions can be placed in flasks or beakers and are popular for the simultaneous agitation of multiple solutions, such as mixing the contents of microplates. Samples in a lab shaker can be agitated via a linear motion or by an orbital motion to create a vortex in the solution. The principal application of shakers is for growing yeast, bacteria, or mammalian cells in specialized containers known as shaker bottles.

The earliest laboratories relied on manual stirring to promote chemical reactions and other processes. However, the early twentieth century saw the introduction of the first dedicated laboratory stirrers which relieved researchers of this task, allowing for more controlled and prolonged stirring and agitation.

1910 to 1940

The first hot plate stirrer was patented in 1917 by Richard Stringham of Utah and consisted of stationary electromagnets built into a hot-plate base. When a reaction vessel such as a flask or beaker was positioned on the stirrer, a bar magnet placed in the solution rotated as a result of the magnetic field created by the electromagnets.

A significant problem of early twentieth century research was the risk of fire from the necessity of heating solutions using a naked flame. This problem was resolved in the 1930s by husband and wife team Glen and Ruth Morey who invented the heating mantle, a reliable and non-flammable heating device with electric resistance wires woven into a fiberglass cloth sheath. The first heating mantle was sold in 1939, and the couple formed the Glas-Col Apparatus Company to manufacture their new product. Although not a stirrer, the heating mantle represents an important stage in the development of heating systems which are often used with an external stirrer.

1940s

The bar magnet used with the first magnetic stirrers was gradually found to be less than ideal, particularly because the iron in the magnet could react with chemicals in the solution and change the course of a reaction. To address this problem, two inventors working independently devised the coated magnetic stirrer bar, which was chemically inert and took no part in the ongoing reaction.

In 1944, Arthur Rosinger of Newark, New Jersey was granted a patent for a coated magnetic stirrer bar that was chemically inert. Rosinger’s stirrer bars were coated in plastic, glass, or porcelain and the stirrer itself featured a rotating magnet rather than electromagnets in the mixer’s base. A very similar device was independently designed by Edward McLaughlin of Greenock, Scotland in the late 1940s, apparently without knowledge of the earlier invention. Dr McLaughlin coined the term “flea” to describe the stirrer bar because of the way it jumped erratically in the flask if the magnet was rotated too quickly. The use of the term “flea” to describe a stirrer bar persists to this day.

In 1949, graduate students at Rutgers University were frustrated in their attempts to isolate an antibioticproducing bacterium for treating infection by the frequent failure of their test tube shaking apparatus. David and Sigmund Freedman at the newly formed New Brunswick Tool & Die Company offered to build a more effective shaking device, creating the first New Brunswick Shaker.

The New Brunswick Shaker was subsequently used in the Nobel-prize winning isolation of streptomycin, creating an instant commercial demand for this instrument.

In 1950, Curt Janke and Max Kunkel, founders of IKA, demonstrated their first magnetic stirrer at the first ACHEMA exhibition following the war.

In 1959, two brothers, Jack A. Kraft and Harold D. Kraft—then working for Scientific Industries—filed for a patent for the first vortex mixer. A vortex mixer is a device consisting of a verticallyoriented, electrically-powered drive shaft attached to a cupped rubber piece. The rubber cup is mounted slightly off-center and therefore oscillates in a circular motion when the motor is switched on. Holding a reaction vessel against the rubber cup creates a vortex in the solution, allowing reagents to mix effectively.

During the 1960s, numerous stirrers and shakers came onto the market, due to demand from scientists engaged in state-of-the-art research. For example, NBS introduced reciprocating shakers for the rigorous mixing of cultures and chemicals, the first water-bath shakers which provided temperature control for culturing microorganisms, as well as multi-tiered shakers for mass screening antibiotic compounds and producing vaccines. NBS also introduced the first refrigerated incubator shaker, Psychrotherm, as well as the Model G25 large-capacity console-style incubator shaker and the G76 water bath shaker, models which can still be found operating in labs today.

Also during this time, researchers working at Kinematica invented the rotor/stator principle which became the accepted standard homogenizing technique for plant and animal tissue. As well, scientific Industries began manufacturing the Vortex Jr. Mixer, the first vortex mixer to be commercially available. In 1964, the company launched the Vortex-Genie, an updated version of the Vortex Jr. Mixer, which became the standard mixing apparatus and the ‘workhorse’ of many laboratories. The Vortex-Genie is the antecedent of many of today’s vortex mixers.

In 1965, the static mixer was invented by C.D. Armeniades and colleagues at the Arthur D. Little Company. A static mixer mixes fluids by creating fluid or laminar flow through a series of fixed, helical elements enclosed within a tubular housing. Kenics Corporation acquired the license for this first static mixer and sold the device under the name of the Kenics Motionless Mixer.

In 1969, D. Freedman of NBS published a paper, “The Shaker in Bioengineering, Process Biochemistry,” systematically documenting how shaker speed, orbit diameter, and flask angle affect oxygen transfer to cultures for the first time. Also, as a result of improving technology, IKA began introducing magnetic stirrers with diecast cases, direct drives, electronic control systems, and silumin hotplates as replacements for belt-driven models with sheet metal casings.

In 1970, Kuhner began manufacturing its first series of large capacity incubator shakers, known as the IRC-1 range. This innovation allowed samples to be mixed under highly controlled conditions of temperature, humidity, and CO2 concentration.

In 1972, Salvador Bonet of the SBS Company revolutionized laboratory stirrers with the concept of multipoint magnetic stirring, allowing different solutions to be stirred simultaneously for the first time under identical conditions. SBS Company eventually developed and patented the world’s first multipoint magnetic stirrer, the historic A-04 model which offered six rotating points. Around this time, SBS also introduced the practice of measuring stirring power in "liters of water"—a market standard today. Also in this year, IKA developed the RW 20 overhead stirrer which became the first device in the industry to bear the prestigious VDE safety mark.

1980s and 1990s

During this period, NBS developed the world’s first microprocessor- controlled shakers, the Innova® range, which marked the beginning of using microchips to precisely control equipment setpoints, alarms, running time, speed and temperature.

Other innovations during the 1980s and 1990s included Kuhner’s first series of shaker cabinets (ISF-4) in 1981, followed in 1989 by its first stackable incubator shakers (ISF-1). The stackable shakers allowed multiple units to occupy the same floor space as a single unit, providing a space-saving option for laboratories.

In 1991, Kuhner introduced its first series of shaker rack systems, a space-saving device that allowed multiple units to be operated independently.

In 2000, NBS added to its Innova range with the benchtop Innova 4200/4230 and large-capacity Innova 4400/4430 which used dual-temperature programming to automate switching between two temperatures on a programmed basis. Automation increased with the NBS Innova 44 stackable shaker in 2003 and the Innova 40 and 43 instruments released in 2005, allowing the user to program for temperature and speed changes as well as recipe capability and other functions.

In 2006, in an attempt to improve the accuracy of mixing speeds and/or times, Scientific Industries launched the Digital Vortex-Genie 2, offering a digital control and display of both time and speed for a more precise and reproducible operation. Also, Velp Scientifica introduced a family of hot plate stirrers, known as AREC, AREC.X, and AREC.T, which incorporated a reflective white ceramic top to help in the observation of color changes and provided resistance to alkali/acid corrosion and chemical attack.

In 2008, Grant Instruments responded to a need for platform shakers able to withstand harsher experimental conditions with the release of its heavy-duty multi-functional orbital shaker. This shaker provided orbital motion, reciprocation and vibration functions all in one instrument controlled by a microprocessor. Also in this year, Radleys devised a cost-effective way to stir up to six round bottom flasks simultaneously without the need to purchase a dedicated multiple stirrer, through an add-on module known as the Tornado. The Tornado was designed to distribute high-torque stirring from the existing Carousel 6 to multiple positions.

In 2008 as well, Scientific Industries updated their popular Vortex- Genie 2 by introducing the multi-vortex genie which used the same technology but allowed multiple vessels to be stirred simultaneously. That same year Boekel Scientific introduced the Flask Dancer Orbital Shaker, designed to offer a more consistent and uniform mixing action. This instrument provided a smooth horizontal mixing motion and could be programmed to operate for periods up to 99 hours without supervision.

In 2009, VELP Scientifica introduced their Vortex WX system which starts vibrating automatically when a sample is inserted, using infra-red to detect the presence of the test tube. The infra-red system ensures vibration is maintained without the need for pressure from the sample. As well, in an attempt to simplify the sheer variety of laboratory stirrers that was now available on the market, Jeio Tech, Inc. introduced a new line of stirrers in three sizes and four colors. The Lab Companion Magnetic Stirrer range was designed for simple usage, offering a range of stirring capacities and speeds.

Another significant product launched in 2009 was the Thermo Scientific MaxQ 8000 range of stackable shakers designed to offer maximum culture capacity but requiring limited lab space. These shakers provided several unique features such as run points and set points for temperature, speed and time, displayed simultaneously for convenient run cycle monitoring. That same year Torrey Pines Scientific, Inc. responded to a demand for instruments offering a wider range of temperatures with the release of the EchoTherm™ SC20XR and SC20XT Digital and Programmable Orbital Mixing Chilling/Heating Dry Baths. These units offered a greater temperature range than existing models, and were also able to change temperature quickly.

In 2010, Johnstown, PA ITSI Biosciences responded to the growing need for compact instrumentation by releasing the small and light ITSI Vortex Mixer and the ITSI Magnetic Stirrer. Both of these instruments are battery-operated, making them easy to move around the laboratory and ideal for field use.

In 2011, Scientific Industries developed a vortex mixer specifically for applications requiring more aggressive action than can be achieved through standard vortexing. The Vortex-Genie pulse delivers a pulsing action to the sample, providing a random motion and a greater number of collisions. This year has also seen Boekel Scientific develop a variation on existing shakers with the Wrist O’Matic Shaker designed to simulate action of the human wrist. These shakers offer a range of mixing amplitude, from a gentle swirl to a very vigorous mixing.

Lastly, in 2011 as well, Grant Instruments released the GLS Aqua Plus series of linear shaking baths which they developed specifically to meet the needs of molecular biologists in applications such as hybridization, bacterial culture media production and for solubility studies.

The future of laboratory shakers and stirrers

Unlike laboratory instruments that develop incrementally over time without any real innovation, the technology in lab shakers and stirrers continues to advance at a faster rate. The future for lab shakers and stirrers is likely to involve the development of instruments that offer alternative mixing actions for more thorough and efficient mixing, possibly mimicking further the action of the human wrist. Other innovations are likely to include instruments capable of mixing more samples simultaneously, and greater integration with other lab processes, allowing for more automation in the laboratory and less human intervention.