Biocal Technology, Inc.

Qiagen Sciences, LLC

Bioptic, Inc.

Varouj D Amirkhanian

Ming-Sun Liu

Paul Mooney

Shou-Kuan Tsai

Bob G Heitel

Andras Guttman

Sing-Tien Chiang

Ming-Jhy Hseu

A method for glycan profiling by capillary electrophoresis (CE), and a CE system for glycan analysis (N-Glycan). The CE system uses integrated dual optical fibers for both radiation excitation and emission detection. The CE system is configured for performing a two-color detection for data analysis. A single radiation excitation source is used to excite two emission fluorophores or dyes in the sample solution to be analyzed. One emission dye is to tag the sample and the other dye is used to provide a reference marker (e.g., a Dextran Ladder) for the sample run. Two detectors (e.g., photomultiplier tubes (PMTs)) are applied to simultaneously detect the fluorescent emissions from the dyes. The data collected by both detectors are correlated (e.g., synchronized, and/or super-positioned for analysis) for accurate data peak identification.

Glycan profiling utilizing capillary electrophoresis

A multi-channel bio-separation system configured to utilize a cartridge that has a individual, separate integrated reagent (i.e., a separation buffer) reservoir dedicated for each separation channel. The multiple channels may have different characteristics, such as different separation medium of different chemistries, different separation length, different channel sizes and internal coatings. In one embodiment, the cartridge does not include integrated detection optics. Not all channels need to be operative. One or more of the channels in the cartridge may be 'dummy channels' that are not operative (e.g., not provided with a capillary tube). A capillary tube may be routed between the reservoir/electrode (anode) of one channel to an electrode (cathode) in another channel, thus allowing a longer length of capillary tube to be used to define a longer separation channel to improve resolution.

Disposable multi-channel bio-analysis cartridge and capillary electrophoresis system for conducting bio-analysis using same

A micro-vial for handling micro-volume of sample fluids. The interior wall defined in the vial has a cylindrical sample section, a wider cylindrical alignment section, a tapered or conical guide section, and a relatively large cylindrical body section, arranged in sequence in that order along the center axis of the vial. The sample section holds a small volume of a sample fluid and receives the tip end of a capillary tube. The alignment section has a larger diameter than the sample section, receiving a cylindrical support that coaxially supports the relatively fragile capillary tube. The tip of the capillary tube dips into the micro-volume of sample fluid held in the sample section. The conical section guides the capillary tube and the support tube into the alignment section and the tip of the capillary tube into the sample section.

Micro-vials

Disposable bio-analysis cartridge

A detection optics configuration for bio-analysis, in which the direction of incident radiation, the axis of the separation channel, and the direction of collection of the output radiation are coplanar at the detection zone. The detection configuration incorporates ball-end optical fibers to direct incident radiation at and collection of output radiation from the detection zone. The detection optics configuration may be implemented in an improved bio-separation instrument, in particular a capillary electrophoresis instrument.

Bio-analysis using ball-ended incident and output optical fibers

A cartridge-based bio-separation system configured to utilize a pen shaped bio-separation cartridge that is easy to assemble and use with no moving parts and that has an integrated reagent (separation buffer) reservoir. The cartridge includes a body, defining an opening as a detection window for receiving external detection optics, at least one capillary column supported in the body, having a first end extending beyond a first end of the body, wherein the detection window exposes a section along the capillary column, to which the external optics are aligned through the detection window, and a reservoir attached to a second end of the body in fluid flow communication with a second end of the capillary column. The reservoir is structured to be coupled to an air pressure pump that pressurizes the gel reservoir to purge and fill the capillaries with buffer as the separation support medium.

Disposible bio-analysis cartridge and instrument for conducting bio-analysis using same

A capillary tube having a hard, optically clear external coating or cladding. In one embodiment, the external clear coating comprises hard-fluoropolymer. The hard-fluoropolymer coating bonds to the fused silica glass, providing higher strength and superior static fatigue performance resulting in vastly improved bending flexibility. The thin hard-fluoropolymer coating of capillaries provides higher initial tensile strength, longer lifetime (resistance to stress corrosion or static fatigue) and superior ability to transmit excitation light and emitted light directly through the coating for fluorescence based detection.

Capillary electrophoresis using clear coated capillary tubes

An apparatus for aligning a capillary column with one or more excitation fibers and with one or more optical lens elements for Capillary Electrophoresis. The apparatus includes two identical blocks having a plurality of grooves for positioning and aligning the capillary column with the one or more excitation fibers, and a plurality of lens seats for optically coupling the lens element with the capillary column. Each block includes a male and female part for mating the two identical blocks together.

Optical detection alignment coupling apparatus

A cost-effective multi-channel capillary gel-electrophoresis system for highly efficient, nucleic acid-based analysis, in particular HLA SSP (Human Leukocyte Antigen Sequence Specific Primer) typing applications. Twelve DNA samples are automatically injected, electrophoretically separated, detected and analyzed simultaneously by using a multiple usage and disposable multi-capillary gel-cartridge. Using commercially available DNA size markers as indicators, the system provides high resolving power with 12-channel separations in less than 1.5 minutes. The system can hold a total of 96 samples in a PCR plate that can automatically be analyzed within 25 minutes for a full plate of the HLA SSP kits.

Method and apparatus for high speed genotyping

An integrated bio-analysis system incorporates built-in sample preparation capabilities. In one aspect of the present invention, a bio-analysis instrument is provided with a built-in sample preparation device based on PCR (or thermal cycling block/module). In one embodiment of the present invention, a peltier unit in the sample preparation device provides thermal cycling of samples supported in a multi-well tray. In another aspect of the present invention, a CE instrument is provided with a built-in sample preparation capability, which may comprise a sample preparation (bio-molecular reaction) device based on thermal cycler type. In another aspect of the present invention, a PCR device is provided with a built-in analysis device, such as a CE device, for verifying the results of the PCR (bio-molecular reaction) process.

Integrated bio-analysis and sample preparation system

A cost-effective multi-channel capillary gel-electrophoresis system for highly efficient, high speed, high throughput, carbohydrate analysis. In one aspect of the present invention, a high-performance capillary electrophoresis analyzer system has been optimized for carbohydrate analysis application. The system uses a multiplexed/time-staggered fluorescence type detection mechanism, with an integrated fiber optic array-based technology and a novel disposable gel-cartridge. Twelve carbohydrate samples are automatically injected, electrophoretically separated, detected and analyzed simultaneously by using a multiple usage and disposable multi-capillary gel-cartridge. Using commercially available labeling agent such as APTS (representing 8-Aminopyrene-1,3,6-trisulfonic acid, trisodium salt) as an indicator, the capillary electrophoresis-based carbohydrate system/analyzer provides high resolving power in 2-15 minutes of separations. The system can hold a total of 96 samples, which can be automatically analyzed within 30-60 minutes. This affordable fiber optic based fluorescence detection system can be used in laboratories for high speed carbohydrate sequencing & screening applications.

Method and apparatus for high speed carbohydrate analysis

A reusable bio-analysis cartridge that includes a built-in mechanism to track various parameters and usage data. The tracking mechanism includes a non-volatile rewritable memory 'smart-key' that is associated with the cartridge to provide automatic tracking dedicated to the cartridge. The key may be physically coupled to the cartridge with good high voltage insulating properties. When the cartridge is used in an instrument, the associated key is inserted into an I/O interface to communicate with the instrument. The instrument may be configured to 'authenticate' the cartridge and conduct an integrity check to determine if the particular cartridge has the correct properties (e.g., gel-chemistry, serial no., Patient I.D.) for the particular sample analysis to be conducted. Further, the instrument may communicate/record information concerning usage of the cartridge (e.g., usage history, test parameters, and perhaps test results). Such information provides an update to the stored information from the previous use of the cartridge.

Bio-analysis cartridge tracking and protection mechanism

The present invention provides for an interface mechanism in a bio-separation instrument that makes interface connections to a multi-channel cartridge. The interface mechanism precisely positions the cartridge in relation to the support elements in the instrument (e.g., high-voltage, gas pressure, incident radiation and detector), and makes automated, reliable and secured alignments and connections between various components in the cartridge and the support elements in the supporting instrument. The interface mechanism comprises pneumatically or electromechanically driven actuators for engaging support elements in the instrument to components on the cartridge. After the cartridge has been securely received by the interface mechanism, the connection sequence is initiated. The interface provides separate high voltage and optical connections for each separation channel in the cartridge, thus providing channel-to-channel isolation from cross talk both electrically and optically.

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La Crescenta, CA, United States of America

Varouj D Amirkhanian