Radiant energy – Fluent material containment – support or transfer means – With irradiating source or radiating fluent material
Reexamination Certificate
2002-08-07
2004-05-11
Lee, John R. (Department: 2881)
Radiant energy
Fluent material containment, support or transfer means
With irradiating source or radiating fluent material
C250S428000, C250S251000, C250S453110, C250S454110, C250S455110, C356S364000, C204S450000, C436S174000, C436S518000, C436S547000, C436S527000, C436S543000, C359S566000
Reexamination Certificate
active
06734436
ABSTRACT:
TECHNICAL FIELD
The present invention relates to the use of electromagnetic radiation to move droplets of fluid on a fluid-transporting surface. In particular, the invention relates to microfluidic devices and methods in which radiation is directed through a material that is substantially transparent to that radiation in order to optically move fluid droplets on a fluid-transporting surface. Typically, optical movement of fluid droplets is achieved while evaporative loss from the droplets is reduced.
BACKGROUND
A number of factors have contributed to the recent advances in the fields of biological sciences, biochemical assays, clinical diagnostics, and synthetic and analytical chemistry. These factors, for example, include the growing significance of genomics, the emergence of proteomics, and developments in combinatorial chemistry. In addition, the rise of drug-resistant forms of infectious diseases, increases in the incidence of food-chain contamination by pathogenic bacteria, the threat of biological warfare, and the continued prevalence of infectious diseases in underdeveloped countries also highlight the need for improved techniques for drug screening, drug target validation, toxicology studies, and combinatorial chemistry.
In these fields, progress has often been limited by the inability to process large numbers of samples at high speed. Extended time frames are necessitated by tedious sample preparation techniques and slow detection methods. These constraints in turn make automation of diagnostic assays difficult and create barriers to driving assay costs down. Thus, there is a current need in the art for rapid and inexpensive techniques to carry out diagnostics, parallel syntheses, and high throughput screening.
Expensive or rare fluids are employed in many emerging scientific applications, such as proteomics and genomics. Thus, considerable interest has been focused on microfluidic techniques, which typically involve small sample volumes and low reagent consumption. In addition, microfluidic techniques may be used to carry out numerous parallel processes, can be used across a range of fluid properties, and are compatible with movement of biological moieties that may vary by orders of magnitude in size and physical characteristics (e.g., from peptide hormones to intact cells). Processes in a microfluidic format are, therefore, particularly amenable to automation, enabling routine screening and surveillance programs to be established. In addition, new process paradigms, such as flow-through processing of biological samples, become feasible only in a microfluidic format.
A variety of microfluidic devices have been developed for chemical and bioanalytical applications. Typically, microfluidic devices involve the miniaturization and automation of a number of laboratory processes, which are then integrated on a chip. Thus, microfluidic technology may be employed to carry out a series of chemical or biochemical processes in a single device, including sample purification, separation, and detection of specific analytes. Applications include medical diagnostics, genetic analysis, or environmental sampling. See, e.g., Ramsey et al. (1995) “Microfabricated chemical measurement systems,”
Nat. Med
. 1:1093-1096.
Microfluidic devices may be constructed using simple manufacturing techniques and are generally inexpensive to produce. For example, the microfabrication methods used to make microchips in the computer industry may also be used to create microfluidic devices, enabling the creation of intricate, minute patterns of interconnected channels. Once a pattern is created, microchip manufacturing methods are employed to recreate the channel design in a substrate. In some instances, chemical etching or stamping techniques are employed. As a result, highly precise channels with dimensions that can be varied in their width and depth may be produced on a substrate. Once the pattern is produced in the substrate, a cover plate is affixed over the substrate so as to form conduits in combination with the channels.
Typically, the substrates and/or cover plates are comprised of a rigid material such as glass (see, e.g., Woolley et al. (1994), “Ultra-high-speed DNA fragment separations using microfabricated capillary array electrophoresis chips,”
Proc. Natl. Acad. Sci. USA
91:11348-11352), plastic (see, e.g., McCormick et al. (1997), “Microchannel electrophoretic separations of DNA in injection-molded plastic substrates,”
Anal. Chem
. 69:2626-2630), silicon, or quartz. Alternatively, microfabricated elastomeric valve and pump systems have been proposed in International Patent Publication No. WO01/01025. Similar valves and pumps are also described in Unger et al. (2000) “Monolithic microfabricated valves and pumps by multilayer soft lithography,”
Science
288:113-116. These publications describe soft lithography as an alternative to silicon-based micromachining as a means by which to form microfluidic devices. Through soft lithography, microfluidic structures created entirely from an elastomer may be constructed containing on/off valves, switching valves, and pumps.
The above-described microfluidic devices, however, pose certain technical challenges that must be overcome. For example, fluid flow characteristics within the small flow channels of a microfluidic device may differ from the flow characteristics of fluids in larger devices, since surface effects tend to predominate, and regions of bulk flow become proportionately smaller. Consequently, several techniques have been developed in order to achieve fluid flow control in microfluidic devices. One commonly used technique involves the generation of electric fields to manipulate buffered, conductive fluids around networks of channels through electrophoretic or electroosmotic forces. See, e.g., Culbertson et al. (2000), “Electroosmotically induced hydraulic pumping on microchips: differential ion transport,”
Anal. Chem
. 72:2285-2291. Another technique, as described in Anderson et al. (2000), “A miniature integrated device for automated multistep genetic assays,”
Nucleic Acids Res
. 28:E60, involves achieving fluidic control by coupling the device to an external system of solenoid valves and pressure sources.
The use of three-dimensional channels to define fluidic pathways, however, gives rise to several limitations. For example, leakage of fluids or analytes into undesired channels through diffusion or the influence of local electric field gradients requires the precise control of bias voltages along each channel in the microfluidic network. This need for precise control increases the design constraints for complex systems and requires that a high degree of engineering sophistication be incorporated into the microfabricated device. In particular, electric field gradients and path length differences around bends or corners in fluidic channels will also distort the distribution of analytes within the sample stream. This distortion can degrade the performance of an electrophoretic separation. In addition, the infrastructure and circuitry required to establish the electric fields are associated with certain spatial requirements that limit the complexity of the microfluidic devices. Furthermore, microvalves and other fluid control mechanisms greatly increase the complexity, cost, and manufacturability of such highly integrated designs.
In some instances, electric fields may be applied to move fluids without the use of three-dimensional channels. For example, U.S. Pat. No. 6,294,063 to Becker et al. describes microfluidic devices that programmably manipulate packets of fluids through the application of electric fields via electrodes located on the devices. A fluid is introduced onto a reaction surface and compartmentalized to form a packet. An adjustable programmable manipulation force is applied to the packet according to the position of the packet. As a result, the packet is programmably moved according to the manipulation force. In some cases, electromagnetic radiation may be used to maintain photochemical reaction or for sensing process
Bashkin John S.
Faris Gregory W.
Heydt Richard P.
MacQueen David
Wright William H.
Lee John R.
Reed & Eberle LLP
SRI - International
Vanore David A.
Wu Louis L.
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