Tools Used for Cell Manipulation

Cell manipulation offers numerous possibilities for the advancement of research in cellular diagnostics, gene delivery, stem cell sorting and for assays that are based on single cells. Direct manipulation of cells is often the more preferred choice because researchers have better access to selection of cells that is more precise, something that averaging a select cell population will not offer. There are several tools that are effective for cell manipulation. These include:

Vacuum technology
Vacuum technology is a technique that uses vacuum to hold cells in order to allow micro injection. This is one of the most commonly used cell manipulation tools. The only disadvantage is that it doesn’t offer enough control for sorting and isolating cells.

Capillary tube method
This method is used to isolate cells through suspension and manipulation using extremely small quantities of phosphate-buffered saline medium. Because this process is based on microsuspension, there is little stress on the cells compared to other methods that use energy and heat absorption.

Microcapillary electrophoresis
This method, once a reliable tool for analytical chemistry, is now used for analyzing microbial cells. Microcapillary electrophoresis may be used in conjunction with fluorescence detection procedures or UV absorption methods. This allows observation of cell staining to observe any metabolic transformation in the enzyme substrates of single cells.

Dielectrophoresis
This technique uses cell lines that secrete insulin and radio frequency to move cells. Cells are manipulated using the electrorotation method and are suspended in the middle of microelectrodes. Using radio frequency signals, a uniformly rotating electric field is generated. The signals produce electric charges that relax the surface and surrounding fluid of the cell.

Optical micromanipulation
Using laser to effect a concentrated radiation pressure on cells allows their manipulation without resorting to direct contact. This tool is modified to make it compatible with a micro-TAS system or a lab-on-a-chip. Using laser-induced fluorescence, optical tweezers and scalpels, cells may be selected, manipulated and analyzed. The tool is refined enough so as to allow cells to be trapped, moved, cut, twisted or pulled.

The only disadvantage to this tool is that it can photodamage the cells, especially if they are too small and extremely fragile. This limits the time that may be spent studying the cells to a few seconds. New research points to the utilization of optical vortex traps that can manipulate cells and its even smaller structures. Using an optical vortex beam (also referred to as the Laguerre-Gaussian beam) that has a dark core will minimize the photodamage to cells usually attributed to the use of lasers.

Electrokinetic micromanipulation
While often used as a tool for microspectroscopy, electrorotation is an effective tool for the micromanipulation of cells. Using a liquid medium, electrokinetic micromanipulation allows cells to be held in place. This allows observation of the cell’s response to other substances.

Piezo impact drive mechanism for microinjection
The piezo impact drive mechanism utilizes mechatronic technologies for cell manipulation. A micro pipette is inserted into the cell’s cytoplasm without causing any deformation, compared to the more traditional hydraulic manipulators.

Micro electromechanical system or MEMS
MEMS are micro-scale tools that allow direct control and manipulation of cells so they can be sorted, isolated and positioned. Using nano particles, tiny vibrations are produced using the device. These cause the particles to adhere to the cell’s surface. The vibrations later convert to heat, incorporating the particles into the cells themselves. A prototype of this device using an SOI or silicon-on-insulator was produced by Toshiba using a mechanical diaphragm that contains diode vibration dishes. This tool is expected to manipulate cells without using any chemical methods.

Biological micro electromechanical system or BioMEMS
This is a broad term that encompasses a group of cell manipulation tools that uses a combination of mechanical, chemical, electrical and microfluidic approaches to analyze cells. The variety of procedures offered by this tool allows the capture, extraction, detection, amplification and purification of cells. This method uses a variety of ways for control, including pressure, electroosmotic flow and acoustic energy. This device not only allows cell manipulation, it also helps in the introduction and mixing of reagents and the detection of analytes.

IR laser tweezers or UV lasers
Using an inverted microscope, cells may be trapped and manipulated in a solution. A single beam or if necessary, multiple beams may be used to perforate cell membrane, depending on the cell size. The cell’s membrane may also be perforated under a microscope using a nitrogen-pulsed laser. It can then be positioned in the proper orientation for further analysis.

Microrobots
With cells suspended in aqueous media, micro-sized manipulators or robotic arms may be used potentially for the manipulation of single cells. These micrometer manipulators are capable of lifting and moving tiny objects within an area measuring 250 micrometers x 100 micrometers, making it a potential contender for cell manipulation technology.