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Micromanipulators are devices intended to translate macroscopic movements of the human hand into microscopic movements of a fine tool held in its grasp. The purpose of its design is to help scientists move very small instruments or tools used in experiments that are conducted under a microscope. Even a skilled surgeon would not have the fine-motor skills required to hold these tiny instruments steady under a high-power microscope, and steady microscopic tools are vital to the success of many experiments. For example, reproductive biologists conducting intracytoplasmic sperm injection (ICSI) use micromanipulators along with microinjection systems to manipulate egg and sperm cells. Electrophysiologists use micromanipulators to make electrical recordings with micropipets from single living cells, such as neurons in brain slices, and to manipulate stimulation electrodes, or perfusion pipets for local application of pharmacological compounds. Micromanipulators are used for a myriad of other purposes, including the dissection of tissue or even single cells, and acute or chronic stereotaxis experiments.
Movement dimension and hand controls
Micromanipulators can be dedicated to movement in one direction, or up to four directions (or dimensions/axes). The number of instruments that a micromanipulator can control simultaneously also varies; you will need to look for one that suits your particular needs. Models that hold single instruments are common, but they range up to micromanipulator platforms that can. Another choice to make is hand controls. Some micromanipulators offer a large dial to turn by hand for each plane of movement, while others accomplish motion control by means of a joystick, or even a remote control.
Several types of movement details are important to consider when perusing micromanipulators. Resolution of movement is denoted as micrometers per step, indicating the finest unit of movement the micromanipulator can effect. Another important detail is the full travel distance, or working range, indicating the distance that the micromanipulator can move the instrument that it is holding. You will probably also see variations in the maximum speeds of travel; this is the fastest rate at which the instrument held by the micromanipulator can travel. The working range, and the maximum speed of travel, might vary for different dimensions, or for fine and coarse controls, as discussed below.
Some micromanipulators designed for use with microscopes combine both coarse and fine movements in one device, for controlling larger and smaller movements, respectively. This allows the researcher to find an instrument such as a micropipet in the microscope’s field of view under the low-power objective, move the micropipet to the desired area of the specimen, center it within the field of view, and then switch to the high-power objective. Here the fine movement control is necessary for tiny, controlled movements such as gently approaching a cell for patch-clamp recordings, or injecting a cell with nuclear material.
Other micromanipulators are dedicated as either coarse or fine. For example, often hydraulic micromanipulators (see below) with a smaller working range are combined with a coarse mechanical or electrical micromanipulator that serves to bring the instrument into the field of view initially. Then the actual experiment is carried out under the higher-power objective using the hydraulic micromanipulator. To make it useful in this role, the coarse micromanipulator will have a longer working range, and a higher maximum speed, than the hydraulic micromanipulator.
Type of drive
Though they share the same overall purpose, micromanipulators differ by generally falling into three categories according to their drive mechanisms, or what controls their movements: direct drive (mechanical), motor/electronic drive, and hydraulic drive. Mechanical, or direct drive, micromanipulators use mechanical gears or cantilevers to reduce macroscopic movements into microscopic ones. Micromanipulators that are powered by electrically driven motors use a similar gear system as the mechanical micromanipulators, but they are driven by electrical motors controlled by either buttons or a joystick. Another type, hydraulic micromanipulators, may also incorporate mechanical elements, but they also rely on the movement of hydraulic fluid. Movements of the human hands are scaled down when hydraulic fluid is transferred between cylinders or pistons of smaller diameters to larger diameters.
Controlling unwanted movements
Unfortunately, there is no such thing as a micromanipulator that holds instruments perfectly still, all the time. But micromanipulator manufacturers continue to strive toward this ideal by developing ways to minimize unwanted movements. A vital characteristic of most micromanipulators is drift and backlash control. This is definitely something to look for if you will be using the micromanipulator to hold fine instruments under high magnification, and/or use specimens requiring great delicacy. Drift is any unwanted movement of the instrument held by the micromanipulator when the operator is not intending to cause movement, and is often reduced with stop locks and springs. Backlash is the unwanted movement of the instrument held by the micromanipulator at the end of an intended movement, and is often minimized by limiting the degrees of freedom in each dimension. Isolation of the micromanipulator from the microscope stage may also reduce drift. Micromanipulators may be self-contained, or may attach to the microscope itself. If you are using a vibration isolation air table, such as in an electrophysiological patch-clamp recording setup, you might prefer to attach the micromanipulator to the air table to minimize unwanted movements.
If drift is a large concern, consider using dedicated coarse and fine micromanipulators as described above. Mechanical micromanipulators are usually ill-suited for higher magnifications, when a turn of the dials will cause the instrument held by the micromanipulator to vibrate. Hydraulic micromanipulators were developed to solve this problem, using either oil or water as the hydraulic fluid. For applications requiring stability of the instrument held by the micromanipulator, such as electrophyiological patch-clamp recordings requiring nearly motionless micropipets, water hydraulics are a better choice‒thermal fluctuations cause more volume changes in oil than in water, which has the effect of creating unwanted drift. A drawback of water as the hydraulic fluid is that it evaporates over time, requiring more frequent maintenance, though usually researchers can replace the water themselves.
By contrast, oil hydraulics tend to be more suitable for applications requiring fast, quick movements. For example, a common use for oil hydraulic micromanipulators are in ICSI, especially in conjunction with a joystick controller. This allows the operator to change directions quickly when trying to capture sperm or egg cells that are floating in media. A drawback of oil as the hydraulic fluid is that it can degrade over time, and might need to be returned to the manufacturer for fluid replacement.
The considerations discussed here can help researchers seeking a micromanipulator by pointing them in the right direction. With the range of micromanipulators available today, there is likely a model out there now that is ready to serve.
Caitlin Smith is a freelance science writer who has a Ph.D. in Neuroscience from Yale University and postdoctoral work in Electrophysiology and Synaptic Plasticity; e-mail: [email protected].
Please check out our Micromanipulator section for more information or to find manufacturers that sell these products