Chemistry: electrical and wave energy – Processes and products – Electrophoresis or electro-osmosis processes and electrolyte...
Reexamination Certificate
2000-10-03
2003-07-22
Nguyen, Nam (Department: 1753)
Chemistry: electrical and wave energy
Processes and products
Electrophoresis or electro-osmosis processes and electrolyte...
C204S643000, C204S450000
Reexamination Certificate
active
06596143
ABSTRACT:
RELATED APPLICATIONS
The present application claims priority to the Chinese patent application entitled “Apparatus For Switching and Manipulating Particles and Method of Use Thereof”, Serial No. 001290436, (NTD Patent & Trademark Agency Limited), filed on Sep. 27, 2000 the disclosure of which is incorporated herein by reference in its entirety.
BACKGROUND OF THE INVENTION
1. Field of the Invention
The invention is concerned with the manipulation of particles, and more particularly, with the manipulation of small particles (e.g., cells, microbeads) using electric fields.
2. Description of the Related Art
The manipulation of particles, especially biological material, can be used to advantage in a variety of biomedical applications. The ability to manipulate individual cancer cells is of particular significance, permitting the researcher to study the interaction of either a single cancer cell or a collection of cancer cells with selected drugs in a carefully controlled environment. Various kinds of forces can be used to manipulate particles, including optical, ultrasonic, mechanical, and hydrodynamic. For example, flow cytometry has been successfully used to sort and characterize cells. Another example is the centrifuge, which has been widely used in laboratories for processing biological samples.
A current trend in the biological and biomedical sciences is the automation and miniaturization of bioanalytical devices. The development of so-called biochip-based microfluidic technologies has been of particular interest. A biochip includes a solid substrate having a surface on which biological, biochemical, and chemical reactions and processes can take place. The substrate may be thin in one dimension and may have a cross-section defined by the other dimensions in the shape of, for example, a rectangle, a circle, an ellipse, or other shapes. A biochip may also include other structures, such as, for example, channels, wells, and electrode elements, which may be incorporated into or fabricated on the substrate for facilitating biological/biochemical/chemical reactions or processes on the substrate. An important goal for researchers has been to develop fully automated and integrated devices that can perform a series of biological and biochemical reactions and procedures. Ideally, such an integrated device should be capable of processing a crude, original biological sample (e.g., blood or urine) by separating and isolating certain particles or bio-particles from the rest of the sample (e.g., cancer cells in blood, fetal nucleated cells in maternal blood, or certain types of bacteria in urine). The isolated particles are then further processed to obtain cellular components (e.g., target cells are lysed to release biomolecules, such as DNA, mRNA and protein molecules). The cellular components of interest are then isolated and processed (e.g., DNA molecules are separated and target sequences are amplified through polymerase-chain-reactions, PCR). Finally, a detection procedure is performed to detect, measure and/or quantify certain reaction products (e.g., a hybridization may be performed on the PCR-amplified DNA segments with fluorescent detection then being used to detect the hybridization result). Clearly, the ability of a biochip to manipulate and process various types of particles, including cells and cellular components from a particle mixture, would be of great significance.
Limited progress has been made to date in the manipulation of particles or bioparticles on a chip. Electronic hybridization technologies have been developed in which charged DNA molecules are manipulated and transported on an electronic chip (e.g., “Rapid Determination of Single Base Mismatch Mutations in DNA Hybrids by Direct Electric Field Control”, Sosnowski, R., et al.,
Proc. Natl. Acad. Sci
., Volume 94, pages 1119-1123, 1997; “Electric Field Directed Nucleic Acid Hybridization on Microchips”, Edman, C.,
Nucl. Acids Res
., 25: pages 4907-4914, 1998, the disclosures of which are incorporated herein by reference in their entireties). Also, electrokinetic pumping and separation technologies have been developed in which biomolecules or other particles can be transported, manipulated, and separated through the use of electroosmosis and electrophoresis based kinetic effects (e.g., “Micromachining a miniaturized capillary electrophoresis-based chemical analysis system on a chip”, Harrison, D. J. et al,
Science
, Volume 261, pages: 895-896, 1993; “High-speed separation of antisense of ligonucleotides on a micro machined capillary electrophoresis device”, Effenhauser, C. S. et al.,
Anal. Chem
. Volume 66, pages: 2949-2953, 1994, the disclosures of which are incorporated herein by reference in their entireties). However, each of these devices suffer from limitations. Accordingly, there is a need for improved particle manipulation devices.
SUMMARY OF THE INVENTION
The present invention relates to the manipulation of particles (including bioparticles such as cells, cell organelles) using traveling-wave dielectrophoresis. The devices and methods of the present invention are suitable for the selective processing and manipulation of one kind of particle in a particle mixture. The devices and methods of the present invention are also capable of concentrating and mixing different types of particles. In addition, the devices and methods of the present invention allow the flexible and easy manipulation and control of a single type or multiple types of particles.
In one embodiment, there is provided a device for producing traveling wave electric fields, which comprises at least three electrically independent branches. Each of the branches comprises a plurality of electrodes capable of producing a traveling wave electric field in its respective branch when the electrodes in its respective branch are connected to out-of-phase signals. The branches meet at a common junction.
In another embodiment, there is provided a device for producing traveling wave electric fields, which comprises at least three sets of electrodes. The sets of electrodes are capable of producing respective traveling wave electric fields in regions adjacent to the sets of electrodes when the electrodes are connected to out-of-phase signals. The sets of electrodes are electrically independent of each other and meet at a common junction.
In another embodiment, there is provided a device for manipulating particles, which comprises at least three sets of electrodes that are electrically independent from each other. The sets of electrodes are capable of generating respective traveling-wave dielectrophoresis (twDEP) forces on particles to move the particles along respective branches when the electrodes in the sets of electrodes are connected to out-of-phase signals, and the branches are interconnected at a common junction to permit the twDEP forces to route particles from one of the branches to another of the branches. In one preferred embodiment of the device, there are three sets of electrodes, and the three sets of electrodes are oriented at about 120 degrees with respect to each other. In another preferred embodiment of the device, there are four sets of electrodes, and the four sets of electrodes are oriented at about 90 degrees with respect to each other. In yet another preferred embodiment of the device, each of the sets of electrodes comprises at least three electrodes. In another preferred embodiment of the device, the device further comprises input tubing which is in fluid communication with a particle source and at least a first one of the sets of electrodes, and may further comprise output tubing in fluid communication with at least a second one of the sets of electrodes (in which the output tubing is in fluid communication with an output reservoir). In one preferred embodiment of the device, the at least three sets of electrodes are disposed on a solid substrate, and the substrate may be selected from the group consisting of silicon, glass, ceramics, and plastics. In another preferred embodiment of the device, the device further comprises a substrat
Cheng Jing
Wang Xiao-Bo
Wu Lei
Xu Junquan
Yang Weiping
Aviva Biosciences Corporation
Knobbe Martens Olson & Bear LLP
Nguyen Nam
Noguerola Alex
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