Electromanipulation is a micro-material analyzing method mostly used for manipulations of biological cells that uses properties of diverse electric fields. In nanotechnology, nanomaterials are so small that they can hardly be directly mechanically manipulated. Hence, electric fields are applied to them to make field-induced movements or deformations. It is a recently developed technology and is still in progress of widening applications. Types of Electronmanipulation includes dielectrophoresis, electro-rotation, electro-deformation, electro-disruption, electro-destruction, electroporation, and electro-fusion. Diverse electromanipulations are achieved using various electric fields including AC(alternating current), DC(direct current), and pulsed(deliver high-energy discharges at very short periods) electrical fields. Electromanipulation of cells permits diverse cell manipulations with minimal mechanical contact between cells and device structures. Although predominantly used in cells, elctromanipulation also contributes to other scientific fields such as Hybridoma technology and nanoelectronic devices development.
There are seven types of electromanipulation, some are drastically different in purpose and function while some are closely related. The most developed and common type is dielectrophoresis. Various manipulations of micro-materials can be achieved using one or several of the seven electromanipulation. Distinct types sometimes require various electric fields or conditions.
Electric field applied: DC or AC oscillating (most cases)
Purpose: displacement
Condition: suspension media of low electrical conductivity; spatially non-uniform electric field [1]
Theory: DEP force is produced by differential polarizability of cells and their suspending medium. There are two types of DEP force, positive DEP(pDEP) and negative DEP(nDEP). pDEP points towards strong regions of the nonuniform electric field while nDEP points towards weak regions of the nonuniform electric field. Live cells can quickly be attracted to the electrode edge when applying DEP, thus separating live cells and dead cells. Dielectric properties of cells can be analyzed using measurements of DEP spectra of cells. [2]
Electric field applied: AC oscillating
Purpose: rotation
Condition: suspension media of low electrical conductivity; frequency is approximately the crossover frequency(DEP force is negligible)
Theory: ER changes the alignment of non-spherical cells by changing the frequency of the oscillating electric field. [2]
Electric field applied: AC oscillating
Purpose: deformation; compare viscoelastic and power-law properties of cells
Condition: suspension media of low electrical conductivity
Theory: ED controls and deforms cells that being attracted to the edge of the electrode edge(by DEP) by increasing AC potential [2]
Electric field applied: pulsed
Purpose: disruption of subcellular structures
Condition: non-uniform electric field
Theory: ED performs electromanipulation inside a cell which has compromised cytoskeletons and a detached nuclei. Deradated cells eject cytosolic contents and become "ghosts"(about 1.5 times the normal cell size). Ghosts can be deflected by pulsed fields and inflected by ac fields. [2]
Electric field applied: pulsed
Purpose: lysis (the disintegration of a cell by rupture of the cell wall or membrane.)
Condition: non-uniform electric field
Theory: pDEP is used to increase the occurrence of lysis, and nDEP is used to decrease the occurrence of lysis. Conditions of cell lysis can be studied by switching pulsing amplitudes. [2]
Electric field applied: pulsed
Purpose: Cell-membrane disruption
Condition: non-uniform electric field; dielectrophoretic alignment of cells
Theory: Cell membrane disruption can be achieved by switching amplitude, duration, pulses rate and number of pulses of the pulsed electric field. When cells' membranes are disrupted, some cells merge into one big cell which can be 3-4 times the size of a normal cell. There are two types of EP: One is irreversible EP which can lead to cytolysis(the bursting of cell membrane when excess water is in the cell); the other is reversible EP which helps maintain cells’ vitality while transforming molecules into cells. [2] [1]
In the early part of 20th century, discoveries of irreversible membrane breakdown and dielectrophoresis are made. Those discoveries serve as fundamental ideas of cellular electromanipulation. In late 20th century, cellular electromanipulation techniques was developed based on the discovery of later discovered reversible membrane breakdown. [3]
Devices for various kinds of electromanipulation are constantly updating, some of newly invented EM devices are introduced in this section. Each device is dedicated to perform a unique kind of electromanipulation.
This multilayer micro-electrode structure is designed for selective manipulation and separation of bioparticles using traveling field dielectrophoresis.
Multilayer micro-electrode structure enables bioparticles to move in a stationary supporting fluid which lead to stationary separations of viable and nonviable yeast cells. It can also achieve transportation of bioparticles in suspended mixtures. It also plays an important role as an integral component contributing to the "biofactory on a chip" technology.
It contains a base portion and a top portion. Each contains one layer of electrodes. The base part consists(from bottom to top):
After the base portion, an insulating layer is applied. On top of the insulating layer is the top part which consists(from bottom to top):
It also contains four electrical busbars to energize traveling field electrode arrays. Electrodes on each side of a channel are aligned with windows between electrodes on the opposite side. Opposing electrodes on each side of a channel were designed to be offset from each other.
An improved device to conduct electroporation was invented by Andrew M. Hoff, Richard Gilbert, Richard Heller, Mark J. Jaroszeski from University of South Florida in 2010.
This device is dedicated to deliver a molecule into a tissue using electroporation.
Spin Crossover complexes are formed by transition metal ions. They can switch between high spin and low spin which leads to changes of magnetic, optical, mechanical properties and more. Dielectrophoresis (DEP) is used to perform molecular spin-state switching. It organizes nano-objects between the electrodes. DEP force aligns the SCO nanorods with the direction of electric field applied. Electromanipulation of spin crossover nanorods is a new field of electromanipulation that are possible building block techniques for nano electronic devices. [6]
Electromanipulation of droplets refers to using electric fields to move or shape small quantities of liquids. When applying a low frequency AC electric field to a high conductive liquid droplet inside a parallel capacitor, the droplet deforms into a new shape. By conducting numerous experiments, an equation which describes the deformation of liquid drop can be summarized. [7]
Electroporation, or electropermeabilization, is a microbiology technique in which an electrical field is applied to cells in order to increase the permeability of the cell membrane, allowing chemicals, drugs, electrode arrays or DNA to be introduced into the cell. In microbiology, the process of electroporation is often used to transform bacteria, yeast, or plant protoplasts by introducing new coding DNA. If bacteria and plasmids are mixed together, the plasmids can be transferred into the bacteria after electroporation, though depending on what is being transferred, cell-penetrating peptides or CellSqueeze could also be used. Electroporation works by passing thousands of volts across suspended cells in an electroporation cuvette. Afterwards, the cells have to be handled carefully until they have had a chance to divide, producing new cells that contain reproduced plasmids. This process is approximately ten times more effective in increasing cell membrane's permeability than chemical transformation.
Electrophysiology is the branch of physiology that studies the electrical properties of biological cells and tissues. It involves measurements of voltage changes or electric current or manipulations on a wide variety of scales from single ion channel proteins to whole organs like the heart. In neuroscience, it includes measurements of the electrical activity of neurons, and, in particular, action potential activity. Recordings of large-scale electric signals from the nervous system, such as electroencephalography, may also be referred to as electrophysiological recordings. They are useful for electrodiagnosis and monitoring.
Digital microfluidics (DMF) is a platform for lab-on-a-chip systems that is based upon the manipulation of microdroplets. Droplets are dispensed, moved, stored, mixed, reacted, or analyzed on a platform with a set of insulated electrodes. Digital microfluidics can be used together with analytical analysis procedures such as mass spectrometry, colorimetry, electrochemical, and electrochemiluminescense.
Electroosmotic flow is the motion of liquid induced by an applied potential across a porous material, capillary tube, membrane, microchannel, or any other fluid conduit. Because electroosmotic velocities are independent of conduit size, as long as the electrical double layer is much smaller than the characteristic length scale of the channel, electroosmotic flow will have little effect. Electroosmotic flow is most significant when in small channels. Electroosmotic flow is an essential component in chemical separation techniques, notably capillary electrophoresis. Electroosmotic flow can occur in natural unfiltered water, as well as buffered solutions.
Electrowetting is the modification of the wetting properties of a surface with an applied electric field.
Electrohydrodynamics (EHD), also known as electro-fluid-dynamics (EFD) or electrokinetics, is the study of the dynamics of electrically charged fluids. It is the study of the motions of ionized particles or molecules and their interactions with electric fields and the surrounding fluid. The term may be considered to be synonymous with the rather elaborate electrostrictive hydrodynamics. ESHD covers the following types of particle and fluid transport mechanisms: electrophoresis, electrokinesis, dielectrophoresis, electro-osmosis, and electrorotation. In general, the phenomena relate to the direct conversion of electrical energy into kinetic energy, and vice versa.
Dielectrophoresis (DEP) is a phenomenon in which a force is exerted on a dielectric particle when it is subjected to a non-uniform electric field. This force does not require the particle to be charged. All particles exhibit dielectrophoretic activity in the presence of electric fields. However, the strength of the force depends strongly on the medium and particles' electrical properties, on the particles' shape and size, as well as on the frequency of the electric field. Consequently, fields of a particular frequency can manipulate particles with great selectivity. This has allowed, for example, the separation of cells or the orientation and manipulation of nanoparticles and nanowires. Furthermore, a study of the change in DEP force as a function of frequency can allow the electrical properties of the particle to be elucidated.
A Coulter counter is an apparatus for counting and sizing particles suspended in electrolytes. The Coulter counter is the commercial term for the technique known as resistive pulse sensing or electrical zone sensing. The apparatus is based on the Coulter principle named after its inventor, Wallace H. Coulter.
Electrosurgery is the application of a high-frequency alternating polarity, electrical current to biological tissue as a means to cut, coagulate, desiccate, or fulgurate tissue. Its benefits include the ability to make precise cuts with limited blood loss. Electrosurgical devices are frequently used during surgical operations helping to prevent blood loss in hospital operating rooms or in outpatient procedures.
Electrochemotherapy is a type of chemotherapy that allows delivery of non-permeant drugs to the cell interior. It is based on the local application of short and intense electric pulses that transiently permeabilize the cell membrane, thus allowing transport of molecules otherwise not permitted by the membrane. Applications for treatment of cutaneous and subcutaneous tumors have reached clinical use by utilizing drugs such as bleomycin or cisplatin). Electrochemotherapy with bleomycin was used to treat a patient for the first time in 1991 at the Institute Gustave Roussy in France, while electrochemotherapy with cisplatin was used to treat for the first time in 1995 at the Institute of Oncology, Ljubljana, Slovenia. Since then, more than 4000 patients were treated with electrochemotherapy all over the world. Recently, new electrochemotherapy modalities have been developed for treatment of internal tumors using surgical procedures, endoscopic routes, or percutaneous approaches to gain access to the treatment area.
There are various classifications of the electro-optical modes of liquid crystal displays (LCDs).
Bio-MEMS is an abbreviation for biomedical microelectromechanical systems. Bio-MEMS have considerable overlap, and is sometimes considered synonymous, with lab-on-a-chip (LOC) and micro total analysis systems (μTAS). Bio-MEMS is typically more focused on mechanical parts and microfabrication technologies made suitable for biological applications. On the other hand, lab-on-a-chip is concerned with miniaturization and integration of laboratory processes and experiments into single chips. In this definition, lab-on-a-chip devices do not strictly have biological applications, although most do or are amenable to be adapted for biological purposes. Similarly, micro total analysis systems may not have biological applications in mind, and are usually dedicated to chemical analysis. A broad definition for bio-MEMS can be used to refer to the science and technology of operating at the microscale for biological and biomedical applications, which may or may not include any electronic or mechanical functions. The interdisciplinary nature of bio-MEMS combines material sciences, clinical sciences, medicine, surgery, electrical engineering, mechanical engineering, optical engineering, chemical engineering, and biomedical engineering. Some of its major applications include genomics, proteomics, molecular diagnostics, point-of-care diagnostics, tissue engineering, single cell analysis and implantable microdevices.
Optoelectrofluidics, also known as optically induced electrohydrodynamics, refers to the study of the motions of particles or molecules and their interactions with optically-induced electric field and the surrounding fluid.
A Nanogenerator converts mechanical or thermal energy as produced by small-scale physical changes into electricity. There are three typical approaches: piezoelectric, triboelectric, both of which convert mechanical motion and pyroelectric nanogenerators which use heat. Both the piezoelectric and triboelectric nanogenerators can convert mechanical energy into electricity. However, pyroelectric nanogenerators can be used to harvest thermal energy from a time-dependent temperature fluctuation.
A capacitive micromachined ultrasonic transducer (CMUT) is a relatively new concept in the field of ultrasonic transducers. Most of the commercial ultrasonic transducers today are based on piezoelectricity. CMUTs are the transducers where the energy transduction is due to change in capacitance. CMUTs are constructed on silicon using micromachining techniques. A cavity is formed in a silicon substrate, and a thin layer suspended on the top of the cavity serves as a membrane on which a metallized layer acts an electrode, together with the silicon substrate which serves as a bottom electrode.
Irreversible electroporation is a soft tissue ablation technique using short but strong electrical fields to create permanent and hence lethal nanopores in the cell membrane, to disrupt cellular homeostasis. The resulting cell death results from induced apoptosis or necrosis induced by either membrane disruption or secondary breakdown of the membrane due to transmembrane transfer of electrolytes and adenosine triphosphate. The main use of IRE lies in tumor ablation in regions where precision and conservation of the extracellular matrix, blood flow and nerves are of importance. The first generation of IRE for clinical use, in the form of the NanoKnife System, became commercially available for research purposes in 2009, solely for the surgical ablation of soft tissue tumors. Cancerous tissue ablation via IRE appears to show significant cancer specific immunological responses which are currently being evaluated alone and in combination with cancer immunotherapy.
Electrohydrodynamic droplet deformation is a phenomenon that occurs when liquid droplets suspended in a second immiscible liquid are exposed to an oscillating electric field. Under these conditions, the droplet will periodically deform between prolate and oblate ellipsoidal shapes. The characteristic frequency and magnitude of the deformation is determined by a balance of electrodynamic, hydrodynamic, and capillary stresses acting on the droplet interface. This phenomenon has been studied extensively both mathematically and experimentally because of the complex fluid dynamics that occur. Characterization and modulation of electrodynamic droplet deformation is of particular interest for engineering applications because of the growing need to improve the performance of complex industrial processes(e.g. two-phase cooling, crude oil demulsification). The primary advantage of using oscillatory droplet deformation to improve these engineering processes is that the phenomenon does not require sophisticated machinery or the introduction of heat sources. This effectively means that improving performance via oscillatory droplet deformation is simple and in no way diminishes the effectiveness of the existing engineering system.
Optoelectrowetting (OEW) is a method of liquid droplet manipulation used in microfluidics applications. This technique builds on the principle of electrowetting, which has proven useful in liquid actuation due to fast switching response times and low power consumption. Where traditional electrowetting runs into challenges, however, such as in the simultaneous manipulation of multiple droplets, OEW presents a lucrative alternative that is both simpler and cheaper to produce. OEW surfaces are easy to fabricate, since they require no lithography, and have real-time, reconfigurable, large-scale manipulation control, due to its reaction to light intensity.
A flowFET is a microfluidic component which allows the rate of flow of liquid in a microfluidic channel to be modulated by the electrical potential applied to it. In this way, it behaves as a microfluidic analogue to the field effect transistor, except that in the flowFET the flow of liquid takes the place of the flow of electric current. Indeed, the name of the flowFET is derived from the naming convention of electronic FETs.
Ohmic heating generates heat by passage of electrical current through food which resists the flow of electricity. Heat is generated rapidly and uniformly in the liquid matrix as well as in particulates, producing a higher quality sterile product that is suitable for aseptic processing.