Chemistry: analytical and immunological testing – Inorganic acid or base
Reexamination Certificate
2001-05-24
2004-06-01
Warden, Jill (Department: 1743)
Chemistry: analytical and immunological testing
Inorganic acid or base
C422S091000, C422S105000, C436S174000, C436S180000
Reexamination Certificate
active
06743636
ABSTRACT:
FIELD OF INVENTION
The present invention relates to a microfluid driving device, especially to a non-contact pneumatic microfluid driving device comprising an external servo system and a chip carrying a microfluid driving platform.
BACKGROUND OF INVENTION
The “biochip” which is able to automatically operate the nucleic acid sample processing and the testing of base series has been developing in all countries the world. In these biochips, the microfluid driving system that drives microfluid that contains samples of biochemical agents to move inside microfluidic channels is one of the most important equipments. The question of how to easily control fluid movement and avoid the cross pollution of the sample or the biochemical agents with the driving system, as become a question of interest.
The microfluid driving system that are known to the public may be divided into three classes. They are the on-chip mechanical micropump, the on-chip electrokinetic micropump and the external servo system. Descriptions thereof will be given as follows:
On-Chip Mechanical Micropump
The on-chip mechanical micropump is an embedded mechanical micropump prepared directly in a chip with the micromachining technology. In an on-chip mechanical micropump, there must have moveable parts in the chip. The electrostatically driven diaphragm micropump invented by Roland Zyngerle et al., U.S. Pat. No. 5,529,456 is one example.
In such a micropump, the micropump includes a pressure chamber. An intermittent electrostatic driving force is generated between the two-layer structure of the pressure chamber and the two one-way passive check valves positioned in the microfluidic channel are driven in turns. Such an operation generates a pumping force to the microfluid. The working flow rate of the micropump is about 350 &mgr;l/min.
The micromachined peristaltic pump invented by Frnak T. Hartley, U.S. Pat. No. 5,705,018 disclosed to another structure. In this invention, a series of flexible conductive strips are provided along the inner wall of the microchannel which is provided in a chip. When voltage pulses pass over the microchannel, the flexible conductive strips are pulled upward by electrostatic force generated in turn. A peristaltic phenomena will thus take place. The microfluid in the microchannel may thus be driven by the driving force of the strips. Working flow rate of this invention is about 100 &mgr;l/min.
In such a mechanical microfluid driving system provided with moveable elements and with a complicated structure, it is very difficult to clean up all residuals of samples or biochemical reagents of another experiment. As a result, most microfluid driving systems for biochips shall be disposable. However, both the embedded rotational micropump and the embedded peristaltic micropump have complicated process of manufacture and expensive customer design components, which made the preparation costs of the micropump relatively high. Such a micropump is not suited in disposable chips.
In addition to that, the mechanical micropumps are generally prepared with membranes, valves or gears which are driven by relatively higher powers, such as electric, magnetic or thermal powers. Such a requirement involves complicated structure, complicated operations and higher costs. Furthermore, it is even more difficult to prepare a pump or pump module that provides driving forces back and forth in the microchannel.
On-Chip Electrokinetic Micropump
The on-chip electrokinetic micropump is a non-mechanical micropump. Inside the pump there are no moveable elements. Operations of such a micropump may be carried on by electro-osmosis (EO), electro-hydrodynamic (EHD) or electrophoresis (EP).
In 1997 Peter J. Zanzucchi et al. disclosed an apparatus and methods for controlling fluid flow in microchannels in their U.S. Pat. No. 5,632,876. This invention related to a microfluid driving system employing the combination of the electro-osmosis power and the electro-hydrodynamic power. The invented apparatus comprises a microchannel provided in a chip and two pairs of electrodes, totally four, are arranged in the microchannel in turn. A pair of electrodes are deeply put in the microchannel. When high voltage is applied to the electrodes, fluid adjacent to the electrodes will be carried in a direction reverse to the direction of the electrical current. An EHD pumping is thus accomplished. Electrodes of the other pair are positioned at both sides from the first pair and contact the walls of the microchannel. When a high voltage is applied to these electrodes, the walls of the microchannel are first electrically charged and charged carriers are accumulated. Electro-osmosis is thus generated in the charge-containing particles in the microfluid and drives the microfluid to flow, carrying out the so-called EO pumping. In this apparatus two kinds of electrode-generated powers are used to generate pumping forces to the microfluid. The microfluid may thus be driven forward, backward or halt inside the microchannel by controlling the ratio of the EHD pumping force and the EO pumping force.
Paul C. H. Li and D. Jed Harrison disclosed a microfluid driving system with the combination of the electro-osmosis power and the electrophoresis power in their article entitled “Transport, manipulation, and reaction of biological cells on-chip using electrokinetic effects (Anal. Chem. 1997, 69,m 1564-1568). In this driving system, electro-osmosis force generators and electrophoresis force generators are arranged in turn in the microchannel. The differences between an electro-osmosis force and an electrophoresis force adjacent to each other, cells in a microfluid may be easily driven to move, direction-turning or even classification. However, the objects moved by the electro-osmosis force or the electrophoresis force are the charge-containing particles in the solution, not the solution itself. As a result, these inventions are not driving systems for microfluids, but rather, are driving systems for charged cells, such as canine erythrocyte et al., in a solution.
From the process point of view, the electrode micropump is simple in structure, low in manufacture cost but limited in application. First, inside the microchannel, solvent must be filled before anything may be driven. It is not possible to introduce samples or reagents into empty channels. Secondly, the distance that an EHD pump can drive a microfluid is limited. The objects that an EO pump or an EP pump drives are charge-containing particles in a microfluid, not the microfluid itself. Neither of these pumps provides satisfactory pumping effects. Working flow rate of these pumps is about 10 &mgr;l/min. In addition, these pumps may only work in microchannels with tiny diameter, e.g., 100 &mgr;m and a voltage difference of hundreds to thousands of volt must be generated within a short distance. High operation costs are thus caused. The EHD pump can only be applied to non-polar organic solvents and the EO pump and the EP pump can only be applied polar solvents. The driving efficiency of the pumps is highly influenced by the concentration of ions in the solution. When the ion concentration of the solution varies during the reaction, driving of the solution will become more difficult to control.
External Servo System
When the microfluid is driven by an external servo system, there is no need to provide any active element in the chip containing the microchannel. Such a chip may be prepared under a lower cost easily. The external servo system is not directly connected to the samples or the reagents and maybe used repeatedly. The problem is the interface between the servo system and the chip, the “system-to-chip interface”. How to connect transmission pipes of carrier fluids, which are in normal sizes, to the microchannels of the chip, which are miniature in size, will become a task to be achieved by using a series of micro fabrication technologies. If the problem of the system-to-chip interface can be solved, the combination of an external servo system and a disposable biochip which contains no active components
Chang Wei-Jieh
Chung Chen-Kuei
Hsiao Chieh-Ling
Weng Kuo-Yao
Bacon & Thomas PLLC
Handy Dwayne K
Industrial Technology Research Institute
Warden Jill
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