Lab-on-a-chip and micro-Total Analysis Systems (mTAS) have generated much excitement in recent years due to their potential to provide high resolution, low cost, and rapid analysis for a wide range of biological and chemical applications. The pursuit of these fully integrated analytical devices has spawned the development of micron scaled technologies to 1) isolate specific cells of interest, 2) amplify the information if necessary, 3) accurately measure an indicator for the cell, and 4) deliver or measure a quantitative result. Electrokinetic tools are attractive and utilized with many of the 1 through 4 stages described due to selectivity and ease of interfacing within microfabricated devices.
This brief discussion focuses on one relatively new electrokinetic technique with far-reaching and versatile appeal: dielectrophoresis (DEP) is the application of an alternating current in a nonuniform geometry. At radio frequencies, cells are selectively controlled due to their inherent intramembrane polarizability characteristics, which cause them to respond uniquely from other cells at specific AC frequencies. Genetically or geometrically similar cells have more similar, but still distinct, responses at given frequencies. The dielectrophoretic force acting on the polarized cell causes it to move either up or down the electric field gradient created by the non- uniform electrode geometry.
Dielectrophoresis can be considered a competitive alternative to the more conventional methods of cell concentration and separation, such as centrifugation, filtration, fluorescence activated cell sorting, or optical tweezers. Because DEP can operate directly on native, unlabeled cells, it eliminates the expense, labor and time of labeling and tagging, as well as the development and validation of such labels and tags. The same basic DEP method has the (probably unique) capability of isolating and analyzing a wide range of particle types (cells, bacteria, viruses, DNA and proteins) using one basic procedure.
After their selective isolation and recovery by DEP, cells remain viable for further analysis, processing or cell therapy. Multiple parameters on individual live cells can be determined and, if desired, specific cell types can be collected. Because it utilizes electronic signals, the technology is capable of extensive automation, is inexpensive and is portable. DEP can also operate under sterile conditions.
Although the ability to selectively isolate cells without harming them is important for many biomedical applications, there are also advantages to be gained by being able to destroy selected target cells. DEP appears capable of achieving this objective. Just as there are limitations in the use of electrofusion and electroporation (mainly associated with the fact that not all cell types can be treated with the same ease, and with irreproducibility between different laboratories), we can expect that efficient and reproducible protocols for selective cell destruction by DEP will not be so easily achieved as the DEP isolation of viable target cells. But it is a worthwhile challenge.
This then prompts the discussion of two possible DEP applications. The first is a pure DEP analysis of an intact cell possibly able to provide enough information that the traditional subcellular efforts to accomplish DNA isolation and polymerase chain reaction (PCR) amplification for genetic detection would be obsolete. The second is to contribute to the first two stages of a mTAS system to nonchemically lyse cells such that the DNA-PCR-detection sequence could continue. We expect to see exciting developments in each of these areas.
In conclusion, dielectrophoretic technologies are an attractive tool with wide-reaching applications in whole cell separation, manipulation, and characterization. However, much work is needed to seamlessly interface DEP modules with other microdevice components in order to attain the sought after lab-on-a-chip, systems. This will require the cooperative pursuit of research into these technologies by individuals in a variety of academic, clinical, and industrial settings. The AES Electrophoresis Society currently strives to facilitate these important dialogues and invites you to become involved at the 2005 Annual Conference in Cincinnati, OH. For additional reading, we suggest the following six articles:
|Adrienne Minerick||Ronald Pethig|