University of California

Joseph W Balch

James Courtney Davidson

Steve P Swierkowski

Raymond P Mariella, Jr

Joseph R Kimbrough

J Courtney Davidson

Laurence R Brewer

Anthony V Carrano

Peter A Krulevitch

M Allen Northrup

Robin R Miles

Xiao-Bo Wang

Jackson C Koo

Peter R C Gascoyne

A process for effectively bonding arbitrary size or shape substrates. The process incorporates vacuum pull down techniques to ensure uniform surface contact during the bonding process. The essence of the process for bonding substrates, such as glass, plastic, or alloys, etc., which have a moderate melting point with a gradual softening point curve, involves the application of an active vacuum source to evacuate interstices between the substrates while at the same time providing a positive force to hold the parts to be bonded in contact. This enables increasing the temperature of the bonding process to ensure that the softening point has been reached and small void areas are filled and come in contact with the opposing substrate. The process is most effective where at least one of the two plates or substrates contain channels or grooves that can be used to apply vacuum between the plates or substrates during the thermal bonding cycle. Also, it is beneficial to provide a vacuum groove or channel near the perimeter of the plates or substrates to ensure bonding of the perimeter of the plates or substrates and reduce the unbonded regions inside the interior region of the plates or substrates.

Plates for vacuum thermal fusion

Manipulation of DNA molecules in solution has become an essential aspect of genetic analyses used for biomedical assays, the identification of hazardous bacterial agents, and in decoding the human genome. Currently, most of the steps involved in preparing a DNA sample for analysis are performed manually and are time, labor, and equipment intensive. These steps include extraction of the DNA from spores or cells, separation of the DNA from other particles and molecules in the solution (e.g. dust, smoke, cell/spore debris, and proteins), and separation of the DNA itself into strands of specific lengths. Dielectrophoresis (DEP), a phenomenon whereby polarizable particles move in response to a gradient in electric field, can be used to manipulate and separate DNA in an automated fashion, considerably reducing the time and expense involved in DNA analyses, as well as allowing for the miniaturization of DNA analysis instruments. These applications include direct transport of DNA, trapping of DNA to allow for its separation from other particles or molecules in the solution, and the separation of DNA into strands of varying lengths.

Microfluidic DNA sample preparation method and device

A sample injection method for horizontal configured multiple chromatography or electrophoresis units, each containing a number of separation/analysis channels, that enables efficient introduction of analyte samples. This method for loading when taken in conjunction with horizontal microchannels allows much reduced sample volumes and a means of sample stacking to greatly reduce the concentration of the sample. This reduction in the amount of sample can lead to great cost savings in sample preparation, particularly in massively parallel applications such as DNA sequencing. The essence of this method is in preparation of the input of the separation channel, the physical sample introduction, and subsequent removal of excess material. By this method, sample volumes of 100 nanoliter to 2 microliters have been used successfully, compared to the typical 5 microliters of sample required by the prior separation/analysis method.

Modified electrokinetic sample injection method in chromatography and electrophoresis analysis

An improved apparatus and method for vacuum fusion bonding of large, patterned glass plates. One or both glass plates are patterned with etched features such as microstructure capillaries and a vacuum pumpout moat, with one plate having at least one hole therethrough for communication with a vacuum pumpout fixture. High accuracy alignment of the plates is accomplished by a temporary clamping fixture until the start of the fusion bonding heat cycle. A complete, void-free fusion bond of seamless, full-strength quality is obtained through the plates; because the glass is heated well into its softening point and because of a large, distributed force that is developed that presses the two plates together from the difference in pressure between the furnace ambient (high pressure) and the channeling and microstructures in the plates (low pressure) due to the vacuum drawn. The apparatus and method may be used to fabricate microcapillary arrays for chemical electrophoresis; for example, any apparatus using a network of microfluidic channels embedded between plates of glass or similar moderate melting point substrates with a gradual softening point curve, or for assembly of glass-based substrates onto larger substrates, such as in flat panel display systems.

Vacuum fusion bonded glass plates having microstructures thereon

A system and method is disclosed for chromatography and electrophoresis using circular optical scanning. One or more rectangular microchannel plates or radial microchannel plates has a set of analysis channels for insertion of molecular samples. One or more scanning devices repeatedly pass over the analysis channels in one direction at a predetermined rotational velocity and with a predetermined rotational radius. The rotational radius may be dynamically varied so as to monitor the molecular sample at various positions along a analysis channel. Sample loading robots may also be used to input molecular samples into the analysis channels. Radial microchannel plates are built from a substrate whose analysis channels are disposed at a non-parallel angle with respect to each other. A first step in the method accesses either a rectangular or radial microchannel plate, having a set of analysis channels, and second step passes a scanning device repeatedly in one direction over the analysis channels. As a third step, the scanning device is passed over the analysis channels at dynamically varying distances from a centerpoint of the scanning device. As a fourth step, molecular samples are loaded into the analysis channels with a robot.

System and method for chromatography and electrophoresis using circular optical scanning

Vacuum fusion bonding of glass plates

A system and method is disclosed for optically locating a microchannel position. A laser source generates a primary laser beam which is directed at a microchannel plate. The microchannel plates include microchannels at various locations. A back-reflectance beam detector receives a back-reflected beam from the plate. The back-reflected beam is generated when the primary beam reflects off of the plate. A photodiode circuit generates a trigger signal when the back-reflected beam exceeds a predetermined threshold, indicating a presence of the microchannel. The method of the present invention includes the steps of generating a primary beam, directing the primary beam to a plate containing a microchannel, receiving from the plate a back-reflected beam generated in response to the primary beam, and generating a trigger signal when the back-reflected beam exceeds a predetermined threshold which corresponds to a presence of the microchannel.

System and method for optically locating microchannel positions

High throughput electrophoresis systems which provide extended well-to-read distances on smaller substrates, thus compacting the overall systems. The electrophoresis systems utilize a high density array of microchannels for electrophoresis analysis with extended read lengths. The microchannel geometry can be used individually or in conjunction to increase the effective length of a separation channel while minimally impacting the packing density of channels. One embodiment uses sinusoidal microchannels, while another embodiment uses plural microchannels interconnected by a via. The extended channel systems can be applied to virtually any type of channel confined chromatography.

Extended length microchannels for high density high throughput

Vacuum pull down method for an enhanced bonding process

A micro injector sample delivery system for charged molecules. The injector is used for collecting and delivering controlled amounts of charged molecule samples for subsequent analysis. The injector delivery system can be scaled to large numbers (&gt;96) for sample delivery to massively parallel high throughput analysis systems. The essence of the injector system is an electric field controllable loading tip including a section of porous material. By applying the appropriate polarity bias potential to the injector tip, charged molecules will migrate into porous material, and by reversing the polarity bias potential the molecules are ejected or forced away from the tip. The invention has application for uptake of charged biological molecules (e.g. proteins, nucleic acids, polymers, etc.) for delivery to analytical systems, and can be used in automated sample delivery systems.

Micro injector sample delivery system for charged molecules

A hybrid slab-microchannel gel electrophoresis system. The hybrid system permits the fabrication of isolated microchannels for biomolecule separations without imposing the constraint of a totally sealed system. The hybrid system is reusable and ultimately much simpler and less costly to manufacture than a closed channel plate system. The hybrid system incorporates a microslab portion of the separation medium above the microchannels, thus at least substantially reducing the possibility of non-uniform field distribution and breakdown due to uncontrollable leakage. A microslab of the sieving matrix is built into the system by using plastic spacer materials and is used to uniformly couple the top plate with the bottom microchannel plate.

Hybrid slab-microchannel gel electrophoresis system

A silicon-based sleeve type chemical reaction chamber that combines heaters, such as doped polysilicon for heating, and bulk silicon for convection cooling. The reaction chamber combines a critical ratio of silicon and silicon nitride to the volume of material to be heated (e.g., a liquid) in order to provide uniform heating, yet low power requirements. The reaction chamber will also allow the introduction of a secondary tube (e.g., plastic) into the reaction sleeve that contains the reaction mixture thereby alleviating any potential materials incompatibility issues. The reaction chamber may be utilized in any chemical reaction system for synthesis or processing of organic, inorganic, or biochemical reactions, such as the polymerase chain reaction (PCR) and/or other DNA reactions, such as the ligase chain reaction, which are examples of a synthetic, thermal-cycling-based reaction. The reaction chamber may also be used in synthesis instruments, particularly those for DNA amplification and synthesis.

Growing community of inventors

Livermore, CA, United States of America

Joseph W Balch