1087 results about "Flow cell" patented technology

The present invention provides an apparatus for analyzing the sequences of polynucleotides. The apparatus comprises (a) flow cell which has at least one microfabricated multilayer elastomeric synthesis channel; and (b) an inlet port and an outlet port. The inlet port and outlet ports are in fluid communication with the flow cell for flowing fluids into and through the flow cell.

The present invention provides methods for determining a nucleic acid sequence by performing successive cycles of duplex extension along a single stranded template. The cycles comprise steps of extension, ligation, and, preferably, cleavage. In certain embodiments the methods make use of extension probes containing phosphorothiolate linkages and employ agents appropriate to cleave such linkages. In certain embodiments the methods make use of extension probes containing an abasic residue or a damaged base and employ agents appropriate to cleave linkages between a nucleoside and an abasic residue and / or agents appropriate to remove a damaged base from a nucleic acid. The invention provides methods of determining information about a sequence using at least two distinguishably labeled probe families. In certain embodiments the methods acquire less than 2 bits of information from each of a plurality of nucleotides in the template in each cycle. In certain embodiments the sequencing reactions are performed on templates attached to beads, which are immobilized in or on a semi-solid support. The invention further provides sets of labeled extension probes containing phosphorothiolate linkages or trigger residues that are suitable for use in the method. In addition, the invention includes performing multiple sequencing reactions on a single template by removing initializing oligonucleotides and extended strands and performing subsequent reactions using different initializing oligonucleotides. The invention further provides efficient methods for preparing templates, particularly for performing sequencing multiple different templates in parallel. The invention also provides methods for performing ligation and cleavage. The invention also provides new libraries of nucleic acid fragments containing paired tags, and methods of preparing microparticles having multiple different templates (e.g., containing paired tags) attached thereto and of sequencing the templates individually. The invention also provides automated sequencing systems, flow cells, image processing methods, and computer-readable media that store computer-executable instructions (e.g., to perform the image-processing methods) and / or sequence information. In certain embodiments the sequence information is stored in a database.

Provided is a surface having metal regions and an interstitial region having a composition that differs from the metal regions, wherein a continuous gel layer coats the surface across the metal regions and the interstitial regions. Nucleic acids or other analytes can be attached to the continuous gel layer such that a greater amount is attached over the metal regions than over the interstitial region. Also provided are methods for making such surfaces. Methods are also provided for making an array of nucleic acids or other analytes using such surfaces.

Methods and devices are provided for controlling a fluid flow over a sensing surface within a flow cell. The methods employ laminar flow techniques to position a fluid flow over one or more discrete sensing areas on the sensing surface of the flow cell. Such methods permit selective sensitization of the discrete sensing areas, and provide selective contact of the discrete sensing areas with a sample fluid flow. Immobilization of a ligand upon the discrete sensing area, followed by selective contact with an analyte contained within the sample fluid flow, allows analysis by a wide variety of techniques. Sensitized sensing surfaces, and sensor devices and systems are also provided.

A system and method for imaging biological samples on multiple surfaces of a support structure are disclosed. The support structure may, for instance, be a flow cell through which a reagent fluid is allowed to flow and interact with the biological samples. Excitation radiation from at least one radiation source may be used to excite the biological samples on multiple surfaces. In this manner, fluorescent emission radiation may be generated from the biological samples and subsequently captured and detected by detection optics and at least one detector. The captured and detected fluorescent emission radiation may then be used to generate image data. This imaging of multiple surfaces may be accomplished either sequentially or simultaneously. In addition, the techniques of the present invention may be used with any type of imaging system. For instance, both epifluorescent and total internal reflection (TIR) methods may benefit from the techniques of the present invention. In addition, the biological samples imaged may be present on the surfaces of the support structure in a random special pattern and need not be at known locations in order for the imaging to be performed.

In embodiments of the present invention, a system and method of cytometry may include presenting a single sperm cell to at least one laser source configured to deliver light to the sperm cell in order to induce bond vibrations in the sperm cell DNA, and detecting the signature of the bond vibrations. The bond vibration signature is used to calculate a DNA content carried by the sperm cell which is used to identify the sperm cell as carrying an X-chromosome or Y-chromosome. Another system and method may include flowing cells past at least one QCL source one-by-one using a fluid handling system, delivering QCL light to a single cell to induce resonant mid-IR absorption by one or more analytes of the cell, and detecting, using a mid-infrared detection facility, the transmitted mid-infrared wavelength light, wherein the transmitted mid-infrared wavelength light is used to identify a cell characteristic.

Provided is a surface having metal regions and an interstitial region having a composition that differs from the metal regions, wherein a continuous gel layer coats the surface across the metal regions and the interstitial regions. Nucleic acids or other analytes can be attached to the continuous gel layer such that a greater amount is attached over the metal regions than over the interstitial region. Also provided are methods for making such surfaces. Methods are also provided for making an array of nucleic acids or other analytes using such surfaces.

Disclosed is a piezoelectric resonator, a process for the fabrication thereof and its use as a sensor element, which implemented in a through-flow cell, is integratable in a measurement system for the determination of the concentration of a substance contained in a liquid and / or for the determination of the physical properties of the liquid. The piezoelectric resonator is designed plane and is provided on its surface with electric contact areas for an electrode and a counter electrode, which is connectable to a signal source as well as to a measurement device. For measuring, the piezoelectric resonator is brought into contact with the to-be-examined liquid on one side, with the resonator responding to the accumulation of the mass of the to-be-detected substance or to a change in the physical properties of the liquid by changing its resonance frequency and / or oscillation amplitude.The present invention is distinguished by the fact that the piezoelectric resonator is provided with contact electrode areas which is contactable from one single side of the resonator. The resonator is the heart piece of a sensor element, which is integrated in a through-flow cell. The through-flow cell us insertable module-like in a measurement arrangement for determining the concentration of a substance contained in a liquid and / or determining the physical properties of the liquid.

A redox flow cell is presented that utilizes a porous membrane separating a first half cell and a second half cell. The porous membrane is chosen to have a figure of merit (FOM) is at least a minimum FOM. A method of providing a porous membrane for a flow cell can include determining a figure of merit; determining a first parameter from a pore size or a thickness for the porous membrane; determining a second parameter from the pore size or the thickness that is not the first parameter for the porous membrane, based on the figure of merit; and constructing a porous membrane having the pore size and the thickness.

PCT No. PCT / US97 / 04398 Sec. 371 Date Sep. 18, 1998 Sec. 102(e) Date Sep. 18, 1998 PCT Filed Mar. 19, 1997 PCT Pub. No. WO97 / 35176 PCT Pub. Date Sep. 25, 1997Improvements in a biosensor of the type having reservoirs or wells for analyzing a biological liquid are disclosed. A biosensor (190) includes a waveguide (164) placed between a plurality of members such as plates (100, 186), at least one of the members (100) being formed to define the walls (132, 134, 136) of the reservoirs where the liquid is biologically analyzed. The walls of the reservoirs are made of an inert, opaque material such as a metal. Although the biosensor may include a gasket (162), the gasket is associated with the members and waveguide in such a way (e.g. by recessing the gasket into a channel formed into a metal plate) so that the gasket does not form any significant portion of the reservoir wall. Waveguides of varying composition (e.g. plastic, quartz or glass) may be associated with the members to form the biosensor. The metal plate of the biosensor has input and output ports for infusing, draining, or oscillating the liquid to be analyzed in the reaction reservoir. Also disclosed is a sled-shaped waveguide associated with a rear lens to couple light out of the waveguide to serve as a quality control measure thus insuring that the biosensor is properly placed and that the light is working.

A cartridge is provided for receiving a sample, including but not limited to blood, urine, and the like. The cartridge includes an input port or dock for receiving a sample from a sample container. A first chamber is in fluid communication with the input port. A flow cell is in fluid communication with the first chamber. The flow cell contains at least one reagent. The reagent can be a calibrant, a fluid containing reactant, a fluid not containing a reactant, a sample, and the like. A pressure port is configured to be coupled to a pressure source, including but not limited to a syringe pump, and the like. A vent port is also provided. The cartridge is configured to maintain fluids in a sealed manner.

A flow cytometer includes an optical flow cell through which particles to be characterized on the basis of at least their respective side-scatter characteristics are caused to flow seriatim. A plane-polarized laser beam produced by a laser diode is used to irradiate the particles as they pass through a focused elliptical spot having its minor axis oriented parallel to the particle flow path. Initially, the plane of polarization of the laser beam extends perpendicular to the path of particles through the flow cell. A half-wave plate or the like is positioned in the laser beam path to rotate the plane of polarization of the laser beam so that it is aligned with the path of particles before it irradiated particles moving along such path.

A flow cell and flow cytometer in which a nozzle at the end of a flow channel is disposed on a removable substrate held at a registered location on a flow cell. Other elements including illumination optics, light collection optics, and the flow cell may then be positioned at fixed locations and would not require subsequent periodic adjustment. The registered location for positioning the nozzle allows removal and replacement of the nozzle key with the nozzle subsequently positioned in the identical location.

A detection apparatus having a read head including a plurality of microfluorometers positioned to simultaneously acquire a plurality of the wide-field images in a common plane; and (b) a translation stage configured to move the read head along a substrate that is in the common plane. The substrate can be a flow cell that is included in a cartridge, the cartridge also including a housing for (i) a sample reservoir; (ii) a fluidic line between the sample reservoir and the flow cell; (iii) several reagent reservoirs in fluid communication with the flow cell, (iv) at least one valve configured to mediate fluid communication between the reservoirs and the flow cell; and (v) at least one pressure source configured to move liquids from the reservoirs to the flow cell. The detection apparatus and cartridge can be used together or independent of each other.

When utilized in a flow imaging instrument, calibration beads provide a known data source that can be employed in various self-diagnostic, calibration and quality metric applications for the both the optical system of the flow imaging instrument, as well as the flow cell of the flow imaging instrument. Such data can be used to determine point spread functions associated with an imaging system, to determine a sensitivity of an imaging system, and to determine a focal point of the imaging system. Imagery collected from calibration beads can be used to determine core size and stability and TDI / flow speed synchronization. Calibration beads can be beneficially employed to enable stable system operation, even when very low sample concentration, or very small sample sizes are to be analyzed.

An integrated detection, flow cell and photonics (DFP) device is provided that comprises a substrate having an array of pixel elements that sense photons during active periods. The substrate and pixel elements form an IC photon detection layer. At least one wave guide is formed on the IC photo detection layer as a photonics layer. An optical isolation layer is formed over at least a portion of the wave guide. A collection of photo resist (PR) walls patterned to define at least one flow cell channel that is configured to direct fluid along a fluid flow path. The wave guides align to extend along the fluid flow path. The flow cell channel is configured to receive samples at sample sites that align with the array of pixel elements.

A method for increasing the throughput, or the precision, or both the precision and the throughput, of a flow cytometer, or of a hematology analyzer employing a flow cytometer, by utilizing the technique of laser rastering. Laser rastering involves sweeping a laser beam across a flowing sample stream in a hematology analyzer. An apparatus suitable for carrying out the method of this invention comprises an optical module comprising a source of light, a scanning device, a lens or system of lenses, a flow cell, detectors, and filters; and an electronic module comprising preamplifiers, analog signal conditioning elements, analog-to-digital converters, field-programmable gate arrays, digital signal processing elements, and data storage elements.

An imaging fountain flow cytometer allows high resolution microscopic imaging of a flowing sample in real time. Cells of interest are in a vertical stream of liquid flowing toward one or more illuminating elements at wavelengths which illuminate fluorescent dyes and cause the cells to fluoresce. A detector detects the fluorescence emission each time a marked cell passes through the focal plane of the detector. A bi-directional syringe pump allows the user to reverse the flow and locate the detected cell in the field of view. The flow cell is mounted on a computer controlled x-y stage, so the user can center a portion of the image on which to zoom or increase magnification. Several computer selectable parfocal objective lenses allow the user to image the entire field of view and then zoom in on the detected cell at substantially higher resolution. The magnified cell is then imaged at the various wavelengths.

A flow cell is disclosed for collecting and concentrating a sample dispersed in a flowing medium. The collected sample can be selectively manipulated within the cell by the use of one or more traveling wave grids. The cells are particularly useful as bio-enrichment devices and can be utilized upstream of conventional analytical or detection instruments.

Microfluidic devices are provided for trapping, isolating, and processing single cells. The microfluidic devices include a cell capture chamber having a cell funnel positioned within the cell capture chamber to direct a cell passing through the cell capture chamber towards one or more a cell traps positioned downstream of the funnel to receive a cell flowing. The devices may further include auxiliary chambers integrated with the cell capture chamber for subsequent processing and assaying of the contents of a captured cell. Methods for cell capture and preparation are also provided that include flowing cells through a chamber, funneling the cells towards a cell trap, capturing a predefined number of the cells within the trap, interrupting the flow of cells, flowing a wash solution through the chamber to remove contaminants from the chamber, and sealing the predefined number of cells in the chamber.

The present invention relates to diagnostic assays whereby the detection means is based on electrochemical reactions. This means that the label to be detected provides an electric signal. Preferred labels are enzymes giving such a signal. Provided is a flow cell whereby a solid phase is provided in a flow stream of the sample, in close proximity to a working electrode to detect any electrical signal. In a typical embodiment, a sample is mixed with molecule having specific binding affinity for an analyte of which the presence in the sample is to be detected, whereby said specific binding molecule is provided with a label. The conjugate of labelled specific binding molecule and analyte is then immobilized on the solid phase in the vicinity of the working electrode, the flow cell is rinsed with a solution and afterwards a substrate solution for the label (an enzyme) is provided upon which an electrical signal is generated and can be detected by the working electrode. The methods and devices of the present invention are particular useful for liquids which comprise many substances that may disturb measurement in conventional assays. The design of the flow cell allows for removal of said interfering substances before measurement. In a preferred embodiment at least part of the solid phase is provided in the form of magnetic beads. In this embodiment the solid phase can be mixed with the sample thereby creating a longer reaction time, a better sensitivity and a higher speed of the assay.

An improved optical flow cell adapted for use in a flow cytometer for differentiating formed bodies (e.g., blood cells). Manufactured from a monolithic transparent material, the improved flow cell has an internal flow channel of polygonal transverse cross-section through which prepared samples can be metered and an external envelope suited to acquisition of optical parameters from formed bodies in such samples. Preferably, such flow cell is formed by a glass-drawing process in which a relatively large glass preform having a rectilinear internal channel of a desired polygonal cross-sectional shape is heated and drawn to achieve a desired cross-sectional area of reduced size. Also disclosed are preferred methods for differentiating formed bodies using the flow cell of the invention.

Improvements in a biosensor of the type having reservoirs or wells for analyzing a biological liquid are disclosed. A biosensor (190) includes a waveguide (164) placed between a plurality of members such as plates (100, 186), at least one of the members (100) being formed to define the walls (132, 134, 136) of the reservoirs where the liquid is biologically analyzed. The walls of the reservoirs are made of an inert, opaque material such as a metal. Although the biosensor may include a gasket (162), the gasket is associated with the members and waveguide in such a way (e.g. by recessing the gasket into a channel formed into a metal plate) so that the gasket does not form any significant portion of the reservoir wall. Waveguides of varying composition (e.g. plastic, quartz or glass) may be associated with the members to form the biosensor. The metal plate of the biosensor has input and output ports for infusing, draining, or oscillating the liquid to be analyzed in the reaction reservoir. Also disclosed is a sled-shaped waveguide associated with a rear lens to couple light out of the waveguide to serve as a quality control measure thus insuring that the biosensor is properly placed and that the light is working.

A flow battery with thermal management is presented. The flow battery is housed in an enclosure where fluid is uniformly circulated about holding tanks of electrolyte to control the temperature inside the enclosure.

A laser light source emits a first light beam irradiating a solution including target particles and being flowed in a flow cell to generate forward scattered light and orthogonal scattered light therefrom. A light emitting diode emits a second light beam irradiating the solution in the flow cell to generate at least one wavelength of fluorescence therefrom. A first detector is adapted to detect the forward scattered light. A second detector is adapted to detect the orthogonal scattered light. At least one third detector is adapted to detect the at least one fluorescence. A first filter is disposed between the flow cell and the third detector and adapted to eliminate scattered light generated from the target particles by the irradiation of the first light beam.

During the light illumination period of a monomer addition cycle in synthesizing an DNA microarray, undesirable reflections of illumination light from various interfaces that the illumination light passes through near the synthesis surface of the substrate may reduce the light-dark contrast, and negatively affect the precision and resolution of the microarray synthesis. The present invention provides an flow cell that reduces the undesired reflections by constructing certain flow cell structures with materials that have similar refractive indexes as that of the solution that is in the oligomer synthesis chamber during the illumination period and / or constructing certain flow cell structures or covering the structures with a layer of a material that has a high extinction coefficient.

Devices for detecting particle sizes and distributions using focused light scattering techniques, by passing a sample through a focused beam of light, are disclosed. In one embodiment, the devices include one or more lasers, whose light is focused into a narrow beam and into a flow cell, and dispersions are passed through the flow cell using hydrodynamic sample injection. In another embodiment, a plurality of lasers is used, optionally with hydrodynamic sample injection. Particles pass through and scatter the light. The scattered light is then detected using scatter and extinction detectors, and, optionally, fluorescence detectors, and the number and size of the particles is determined. Particles in the size range of 0.1 to 10 μm can be measured. Using the device, significantly smaller particles can be detected than if techniques such as EQELS, flow cytometry, and other conventional devices for measuring biological particles.