HELICOS BIOSCIENCES CORPORATION Patent applications |
Patent application number | Title | Published |
20120040340 | NUCLEOTIDE ANALOGS - The invention provides for nucleotide analogs and methods of using the same, e.g., for sequencing nucleic acids. | 02-16-2012 |
20120028822 | METHODS, FLOW CELLS AND SYSTEMS FOR SINGLE CELL ANALYSIS - A method, flow cell and/or device for increasing the recovery of a limiting analyte in a sample, e.g., for single molecule analysis is disclosed. Methods for preparing a nucleic acid sample from a single cell and capturing nucleic acids on a surface configured for use in or with single molecule analysis are also provided. | 02-02-2012 |
20120015353 | METHOD OF DETERMINING THE NUCLEOTIDE SEQUENCE OF OLIGONUCLEOTIDES AND DNA MOLECULES - The present invention relates to a novel method for analyzing nucleic acid sequences based on real-time detection of DNA polymerase-catalyzed incorporation of each of the four nucleotide bases, supplied individually and serially in a microfluidic system, to a reaction cell containing a template system comprising a DNA fragment of unknown sequence and an oligonucleotide primer. Incorporation of a nucleotide base into the template system can be detected by any of a variety of methods including but not limited to fluorescence and chemiluminescence detection. Alternatively, microcalorimetic detection of the heat generated by the incorporation of a nucleotide into the extending template system using thermopile, thermistor and refractive index measurements can be used to detect extension reactions. | 01-19-2012 |
20110301042 | METHODS OF SAMPLE ENCODING FOR MULTIPLEX ANALYSIS OF SAMPLES BY SINGLE MOLECULE SEQUENCING - The invention generally relates to methods for sequencing a plurality of nucleic acids from different samples. In certain embodiments, methods of the invention provide contacting a nucleic acid duplex including a primer nucleic acid hybridized to a template nucleic acid with a polymerase enzyme in the presence of a first detectably labeled nucleotide under conditions that permit the polymerase to add nucleotides to the primer in a template-dependent manner, in which a unique oligonucleotide sequence is attached to the template nucleic acid so that the template nucleic acid may be differentiated from other template nucleic acid molecules, detecting a signal from the incorporated labeled nucleotide, and sequentially repeating the contacting and detecting steps at least once, wherein sequential detection of incorporated labeled nucleotide determines the sequence of the nucleic acid. | 12-08-2011 |
20110287426 | Apparatus and Methods for Analyzing Samples - The present invention relates to apparatus, systems, and methods for analyzing biological samples. The apparatus, systems, and methods can involve using a vacuum source to pull microfluidic volumes through analytical equipment, such as flow cells and the like. Additionally, the invention involves using optical equipment in conjunction with the analytical equipment to analyze samples and control the operation thereof. | 11-24-2011 |
20110245086 | SHORT CYCLE METHODS FOR SEQUENCING POLYNUCLEOTIDES - The invention provides methods for sequencing a polynucleotide comprising stopping an extension cycle in a sequence by synthesis reaction before the reaction has run to near or full completion. | 10-06-2011 |
20110152114 | SHORT CYCLE METHODS FOR SEQUENCING POLYNUCLEOTIDES - The invention provides methods for sequencing a polynucleotide comprising stopping an extension cycle in a sequence by synthesis reaction before the reaction has run to near or full completion. | 06-23-2011 |
20110151449 | SHORT CYCLE METHODS FOR SEQUENCING POLYNUCLEOTIDES - The invention provides methods for sequencing a polynucleotide comprising stopping an extension cycle in a sequence by synthesis reaction before the reaction has run to near or full completion. | 06-23-2011 |
20110129827 | METHODS FOR TRANSCRIPT ANALYSIS - The invention takes a unique approach to transcript analysis that provides a novel DGE technology based on single-molecule sequencing. More particularly, the invention relates to methods and compositions for analyzing and identifying genes and gene expression and transcript profiles using a DGE-based technology and single molecule sequencing that does not require amplification or fragmentation. | 06-02-2011 |
20110091883 | METHODS FOR ANALYZING MINUTE CELLULAR NUCLEIC ACIDS - The invention generally relates to methods for analyzing cellular nucleic acid. Methods of the invention involve capturing RNA from a lysed cell onto a substrate, producing a cDNA/RNA duplex, removing the RNA from the cDNA/RNA duplex, priming the cDNA to produce a primer/cDNA duplex, exposing the primer/cDNA duplex to at least one detectably labeled nucleotide in the presence of a polymerase capable of catalyzing addition of the nucleotide to the primer/cDNA duplex, detecting incorporation of the nucleotide into the primer portion, and repeating the exposing and detecting steps at least once. | 04-21-2011 |
20110081647 | NUCLEOTIDE ANALOGS - The invention generally relates to nucleotide analogs and methods of their use in sequencing-by-synthesis reactions. In certain embodiments, the invention provides a nucleotide analog including a detectable label attached to a nitrogenous base portion of a nucleotide analog by a cleavable linker, in which contact of the analog with at least one activating agent results in cleavage of the label and elimination of the linker, thereby producing a natural nucleotide, a 9-deaza-G, 9-deaza-A, or ψ-uridine. | 04-07-2011 |
20110027790 | METHODS OF EQUALIZING REPRESENTATION LEVELS OF NUCLEIC ACID TARGETS - The disclosure provides methods of reducing the range of representation levels of nucleic acid targets. The methods are particularly useful for multi-target analyses benefiting from a low variance of target representations, such as, e.g., single molecule sequencing and/or heterozygous genotyping, and pathogen diagnosis. Two general methods are provided. In Method 1, starting concentrations of probes are adjusted. In Method 2, target-specific probes are “binned,” i.e., several subsets of probes are selected based on similar representation levels. Thereafter, each subset of corresponding targets is extracted, with or without amplification, using a separate portion of the sample (i.e., separate vessels). | 02-03-2011 |
20100304447 | PAIRED-END READS IN SEQUENCING BY SYNTHESIS - The disclosure provides methods of generating paired reads in sequencing-by-synthesis process, particularly, in systems with relatively short read lengths (e.g., 15-35 bases), such as for example, in single molecule sequencing by synthesis. Several implementations of the methods are provided. Of particular advantage are the methods that permit re-sequencing of the template, which yields lower error rates. The invention further provides methods of using paired reads, for example, for positioning them over repeats or for assembly into large sequences, including whole genome assembly. | 12-02-2010 |
20100233697 | METHOD FOR STANDARIZING SURFACE BINDING OF A NUCLEIC ACID SAMPLE FOR SEQUENCING ANALYSIS - Methods are described which enable nucleic acid sample standardization prior to anchoring to a surface, especially useful in single molecule nucleic acid sequencing applications when sample is limiting or unamplified. | 09-16-2010 |
20100233696 | METHODS, FLOW CELLS AND SYSTEMS FOR SINGLE CELL ANALYSIS - A method, flow cell and/or device for increasing the recovery of a limiting analyte in a sample, e.g., for single molecule analysis is disclosed. Methods for preparing a nucleic acid sample from a single cell and capturing nucleic acids on a surface configured for use in or with single molecule analysis are also provided. | 09-16-2010 |
20100227321 | METHODS AND DEVICES FOR NUCLEIC ACID SEQUENCE DETERMINATION - Methods of the invention comprise methods and devices for nucleic acid sequence determination. Generally, the invention relates to preparing a substrate for sequencing a target nucleic acid | 09-09-2010 |
20100216153 | METHODS FOR DETECTING FETAL NUCLEIC ACIDS AND DIAGNOSING FETAL ABNORMALITIES - The invention generally relates to methods for detecting fetal nucleic acids and methods for diagnosing fetal abnormalities. In certain embodiments, the invention provides methods for determining whether fetal nucleic acid is present in a maternal sample including obtaining a maternal sample suspected to include fetal nucleic acids, and performing a sequencing reaction on the sample to determine presence of at least a portion of a Y chromosome in the sample, thereby determining that fetal nucleic acid is present in the sample. In other embodiments, the invention provides methods for quantitative or qualitative analysis to detect fetal nucleic acid in a maternal sample, regardless of the ability to detect the Y chromosome, particularly for samples including normal nucleic acids from a female fetus. | 08-26-2010 |
20100216151 | METHODS FOR DETECTING FETAL NUCLEIC ACIDS AND DIAGNOSING FETAL ABNORMALITIES - The invention generally relates to methods for detecting fetal nucleic acids and methods for diagnosing fetal abnormalities. In certain embodiments, the invention provides methods for determining whether fetal nucleic acid is present in a maternal sample including obtaining a maternal sample suspected to include fetal nucleic acids, and performing a sequencing reaction on the sample to determine presence of at least a portion of a Y chromosome in the sample, thereby determining that fetal nucleic acid is present in the sample. In other embodiments, the invention provides methods for quantitative or qualitative analysis to detect fetal nucleic acid in a maternal sample, regardless of the ability to detect the Y chromosome, particularly for samples including normal nucleic acids from a female fetus. | 08-26-2010 |
20100203541 | NUCLEOTIDE ANALOGS - The disclosure provides nucleotide analogs and methods of their use. Analogs of the invention comprise a reporter molecule (label) attached via the N4, N6, O4, or O6 position of the nitrogenous base portion of the analog. In a preferred embodiment, nucleotide analogs of the invention comprise a label attached to the nitrogenous base portion of the analog via a cleavable linker at the N4, O4, N6 or O6 position. | 08-12-2010 |
20100203524 | POLYMERASES AND METHODS OF USE THEREOF - The invention generally relates to polymerases for efficient and controlled sequencing-by-synthesis reactions. In certain embodiments, the invention provides a polymerase enzyme including at least one mutation that enhances ability of the polymerase as compared to a wild-type polymerase to incorporate a nucleotide into a nascent strand of DNA or cDNA including at least one modified nucleotide. | 08-12-2010 |
20100190168 | COMPETITOR MOLECULES USEFUL FOR LOWERING NONSPECIFIC ADSORPTION OF DYE LABELED NUCLEOTIDES - Methods are described which enable higher signal/noise when performing surface measurements at the single molecule level. Methods are particularly useful in the field of molecular biology when performing single molecule nucleic acid sequencing by synthesis using dye labeled nucleotides. The method employs using a competitor molecule which blocks nonspecific binding of analog molecules to the surface. | 07-29-2010 |
20100184045 | Methods for sequencing degraded or modified nucleic acids - The invention provides methods and compositions for sequencing DNA or RNA samples that would be impossible to do via standard means. Samples that are part of mixtures or are degraded or modified may be sequenced so that the individual from whom the sample originated can be determined or useful biological information can be associated with the sample. Methods are described that allow high efficiency sequencing of degraded nucleic acid samples such as are typically found with FFPE. Samples from severely degraded sources or that have been treated with preservatives such as formalin may be sequenced. In addition to permitting identification of samples, information about disease or treatment status may also be determined. | 07-22-2010 |
20100173363 | Use of Single-Stranded Nucleic Acid Binding Proteins in Sequencing - The invention provides methods for stabilizing a nucleic acid sequencing reaction. Generally, methods of the invention include exposing a target nucleic acid to a single-stranded nucleic acid binding protein and performing a sequencing reaction. | 07-08-2010 |
20100159533 | SIMPLIFIED SAMPLE PREPARATION FOR RNA ANALYSIS - Methods and kits for selective preparing cDNA relatively free of sequences found in rRNA and subcellular RNAs are disclosed. The methods and kits utilize approximately 200 hexamer sequences which target messenger RNA. The methods and kits are useful in preparing samples for sequencing analysis, especially when performing single molecule sequencing by synthesis. | 06-24-2010 |
20100143932 | SINGLE MOLECULE SEQUENCING OF CAPTURED NUCLEIC ACIDS - The invention provides methods and devices for detecting, enumerating or identifying target nucleic acid molecules using immobilized capture probes and single molecule sequencing techniques. | 06-10-2010 |
20100143922 | METHODS FOR REDUCING OVER-REPRESENTATION OF FRAGMENT ENDS - Methods for preparing fragments for nucleic acids sequence analysis that demonstrates uniform coverage across the full fragment length. The methods disclosed herein are useful for candidate gene re-sequencing wherein the detailed analysis is performed on selected, amplified regions of the genome. | 06-10-2010 |
20100091289 | APPARATUS AND METHODS FOR ANALYZING SAMPLES - The present invention relates to apparatus, systems, and methods for analyzing biological samples. The apparatus, systems, and methods can involve using a vacuum source to pull microfluidic volumes through analytical equipment, such as flow cells and the like. Additionally, the invention involves using optical equipment in conjunction with the analytical equipment to analyze samples and control the operation thereof. | 04-15-2010 |
20100034444 | IMAGE ANALYSIS - Image processing for certain sequencing technologies requires data processing algorithms that provide fast sequence detection with low error rates. Methods and apparatus for performing image analysis for identifying nucleotide incorporations includes performing an image segmentation procedure on a plurality of data sets to identify sample objects and to create segmented data sets for each of the data sets. Each data set represents a sample image that includes a plurality of pixel locations and intensity data associated with each of the pixel locations. The segmented data sets represent identified sample objects for each one of the sample image data sets. An image registration procedure is performed on the segmented data sets to align the identified sample objects and to create data representative of the aligned identified sample objects. A strand formation procedure is then performed on the data representative of the aligned identified sample objects to identify nucleotide incorporations. | 02-11-2010 |
20090275034 | TEMPERATURE CONTROL SYSTEM - Single molecule technologies generally require sensitive optical detection and the ability to operate at multiple temperatures simultaneously in different parts of the instrument. The system for controlling the temperature of a microfluidic device and methods for controlling the temperature of sequencing reactions includes a chamber for receiving a microfluidic device, a heating control device in fluid communication with the chamber for delivering a heated fluid to the chamber to heat the microfluidic device, and a cooling control device in liquid communication with the chamber for delivering a cooled fluid to the chamber to cool the microfluidic device. A temperature control unit in liquid communication with a cooling element and/or a heating element are used to regulate temperature of sequencing substrates and objective lenses for optical detection of sequencing reactions. | 11-05-2009 |
20090253141 | METHODS AND APPARATUSES FOR ANALYZING POLYNUCLEOTIDE SEQUENCES - Methods for high speed, high throughput analysis of polynucleotide sequences, and apparatuses with which to carry out the methods are provided in the invention. | 10-08-2009 |
20090249949 | METHODS AND DEVICES FOR BUBBLE MITIGATION - The invention relates to methods, systems and devices for mitigation of bubbles in a micro-fluidic environment. For example, the invention relates to methods, systems and devices for mitigation of bubbles from reagents, solvents, formulations and for improving chemical reactions in micro-fluidic systems, such as for fluorescence detection and polynucleotide sequencing. | 10-08-2009 |
20090246760 | METHODS OF EQUALIZING REPRESENTATION LEVELS OF NUCLEIC ACID TARGETS - The disclosure provides methods of reducing the range of representation levels of nucleic acid targets. The methods are particularly useful for multi-target analyses benefiting from a low variance of target representations, such as, e.g., single molecule sequencing and/or heterozygous genotyping, and pathogen diagnosis. Two general methods are provided. In Method 1, starting concentrations of probes are adjusted. In Method 2, target-specific probes are “binned,” i.e., several subsets of probes are selected based on similar representation levels. Thereafter, each subset of corresponding targets is extracted, with or without amplification, using a separate portion of the sample (i.e., separate vessels). | 10-01-2009 |
20090246085 | Liquid Handling System and Methods for Mixing and Delivering Liquid Reagents - A liquid storage apparatus provides a safe and easy to use device for efficiently managing liquid reagents used in a variety of laboratory equipment. The liquid storage apparatus helps reduce the likelihood of accidents, allows for flexibility of experimental design, and helps maximize the use of chemical regents to prevent waste. The apparatus includes a plurality of containers with a pierceable septum interface at each end. The apparatus also includes a lower array of needles with each of the lower needles in the lower array of needles arranged to penetrate the bottom pierceable septum of a different one of the containers. The apparatus further includes a piercing device arranged to penetrate the top pierceable septum of a different one of the containers. Each of the piercing devices include a passageway so gas can flow into the pierced container. | 10-01-2009 |
20090240441 | SYSTEM AND METHOD FOR ANALYSIS AND PRESENTATION OF GENOMIC DATA - A method for analyzing genomic data that includes obtaining genomic sequence information from an anonymous individual, processing the information via a secure computerized algorithm, and presenting phenotypic information to the individual based upon the genomic sequence information. | 09-24-2009 |
20090233303 | METHODS FOR ASSESSING BREAKDOWN PRODUCTS AND STABILITY OF SIRNA AND OTHER TARGET OLIGONUCLEOTIDES - The disclosure provides methods and compositions for assessing by sequencing the type and quantity of in vivo or in vitro breakdown products and stability of nucleic acids such as small interfering RNA (siRNA) and other target oligonucleotides. In general, the disclosed methods involve the use of tester oligonucleotides that comprise a double-stranded region, an optional loop (in the case of hairpin testers), and a single-stranded 3′ overhang that is complementary to the full-length and a shortened target oligonucleotide. A tester is designed so that the 3′ end of a respective target oligonucleotide anneals to the overhang immediately adjacent to the 5′ end of the tester. The juxtaposed ends of the tester and target at adjacent positions allow for a ligase to ligate the chain if there is a match between a tester and its respective target. By sequencing the ligated product in the region of the ligation site, one may determine the sequence of the 3′ end of the target oligonucleotide or of the entire target and its relative amount in the sample. | 09-17-2009 |
20090197257 | PAIRED-END READS IN SEQUENCING BY SYNTHESIS - The disclosure provides methods of generating paired reads in sequencing-by-synthesis process, particularly, in systems with relatively short read lengths (e.g., 15-35 bases), such as for example, in single molecule sequencing by synthesis. Several implementations of the methods are provided. Of particular advantage are the methods that permit re-sequencing of the template, which yields lower error rates. The invention further provides methods of using paired reads, for example, for positioning them over repeats or for assembly into large sequences, including whole genome assembly. | 08-06-2009 |
20090191565 | SHORT CYCLE METHODS FOR SEQUENCING POLYNUCLEOTIDES - The invention provides methods for sequencing a polynucleotide comprising stopping an extension cycle in a sequence by synthesis reaction before the reaction has run to near or fill completion. | 07-30-2009 |
20090186771 | NUCLEOTIDE ANALOGS - The invention provides nucleotide analogs for use in sequencing nucleic acid molecules. | 07-23-2009 |
20090186351 | NUCLEOTIDE ANALOGS - The invention provides for nucleotide analogs and methods of using the same, e.g., for sequencing nucleic acids. | 07-23-2009 |
20090163366 | TWO-PRIMER SEQUENCING FOR HIGH-THROUGHPUT EXPRESSION ANALYSIS - The disclosure provides a method of sequencing a nucleic acid molecule that contains two or more target regions to be sequenced (such as, for example, barcodes). The invention is advantageous for sequencing by synthesis two or more target regions whose combined lengths plus the length of any intermediate sequence exceeds the available read length on a given sequencing platform. The methods of the invention utilize nucleic acid constructs containing at least the following elements: a complement of a first universal primer, a first target sequence, an optional polynucleotide spacer, a complement of a second universal primer, and a second target sequence. A first round of sequencing by synthesis is performed to sequence the first target sequence by elongating the first universal primer. Once the sequence of the first target region is obtained, and before the complement of the second primer is reached, the first round of sequencing is terminated. Thereafter, a second round of sequencing by synthesis is initiated—this time, by elongating the second universal primer, thereby sequencing the second target region. | 06-25-2009 |
20090156412 | SURFACE-CAPTURE OF TARGET NUCLEIC ACIDS - The disclosure provides methods of capturing target nucleic acids (e.g., gene or gene fragments) onto a solid support for further analysis. The disclosed methods utilize a capture probe that selectively circularizes only the target nucleic acid. Following the circularization of the target, the linear, non-target, nucleic acids are removed from the sample. Next, the circularized target is linearized and bound to a solid support. To allow for linearization, the capture probe may include a cleavage site that can be a noncanonical nucleotide(s) (e.g., uracil in DNA) and/or a rare-cutter site (e.g., the Not I restriction site). In some embodiments, the target nucleic acid is captured onto a support without an intermediate amplification step. | 06-18-2009 |
20090129980 | Multi-Channel Flow Cells - A multi-channel flow cell can allow for reduced cross-contamination in sample loading and the ability to observe activity within the flow cell once the channels are loaded. A multi-channel flow cell includes a plurality of independently-addressable channels sandwiched between a two substrates. Each of the channels can be coated with a layer that facilitates support-binding of an analyte. Each of the channels terminates on one end in an inlet and on the other end in an outlet. A loading block having inlet ports that match the inlets of the channels can be mated to the inlets of the channels, and an outlet block can be mated to the outlets of the channels. Analytes can be introduced into the channels via the inlet ports of the loading block and are pulled through the channels by capillary action or by vacuum. Once analyte has been introduced into each of the channels, the loading and outlet blocks can be removed and the device turned over Such a flow cell can be used for streamlining the process of reaction and interrogation of biochemical assays at the microfluidic level. Reagents can be introduced into each of the channels of the flow cell for chemical reactions therein, excess reagent being washed out through the channel outlets. Observation of optically-detectable moieties is then conducted. With such a flow cell optical labels associated with incorporation in a sequencing-by-synthesis reaction can be observed. | 05-21-2009 |
20090075252 | Methods for increasing accuracy of nucleic acid sequencing - The invention provides methods for improving the fidelity of a sequencing-by-synthesis reaction by resequencing at least a portion of a nucleic acid template. | 03-19-2009 |
20090061439 | Methods and Compositions for Sequencing A Nucleic Acid - The invention provides nucleotide analogs and methods of using them in sequencing reactions. | 03-05-2009 |
20090061437 | Nucleotide Analogs - The invention provides for nucleotide analogs and methods of using the same, e.g., for sequencing nucleic acids. | 03-05-2009 |
20090053705 | METHODS FOR INCREASING ACCURACY OF NUCLEIC ACID SEQUENCING - The invention provides methods for improving the accuracy of a sequencing-by-synthesis reaction by sequencing at least a portion of a template and at least a portion of template complementary sequence. | 02-26-2009 |
20080287306 | Methods and devices for sequencing nucleic acids - The invention provides methods and devices for high throughput single molecule sequencing of a plurality of target nucleic acids using a universal primer. Devices of the invention comprise a plurality of oligonucleotides, each having the same sequence, bound to a solid support, and ligated to a plurality of target nucleic acids. | 11-20-2008 |
20080286837 | Nucleotide analogs - The disclosure provides nucleotide analogs and methods of their use. Analogs of the invention comprise a reporter molecule (label) attached via the N4, N6, O4, or O6 position of the nitrogenous base portion of the analog. In a preferred embodiment, nucleotide analogs of the invention comprise a label attached to the nitrogenous base portion of the analog via a cleavable linker at the N4, O4, N6 or O6 position. | 11-20-2008 |
20080269476 | Molecules and methods for nucleic acid sequencing - The invention provides molecules and methods for nucleic acid synthesis reactions useful in sequencing-by-synthesis processes. | 10-30-2008 |
20080246949 | OPTICAL TRAIN AND METHOD FOR TIRF SINGLE MOLECULE DETECTION AND ANALYSIS - In one aspect the invention relates to an apparatus for analyzing the presence of a single molecule using total internal reflection. In one embodiment an apparatus for single molecule analysis includes a support having a sample located thereon; two sources of light at distinct wavelengths, a collimator for directing the light onto the sample through a total internal reflection objective; a receiver for receiving a fluorescent emission produced by a single molecule in the sample in response to the light; and a detector for detecting each of the wavelengths in the fluorescent emission. In another embodiment the apparatus further comprises a focusing laser for maintaining focus of the objective on the sample. | 10-09-2008 |
20080239304 | Apparatus and Methods for Analyzing Samples - The present invention relates to apparatus, systems, and methods for analyzing biological samples. The apparatus, systems, and methods can involve using a vacuum source to pull microfluidic volumes through analytical equipment, such as flow cells and the like. Additionally, the invention involves using optical equipment in conjunction with the analytical equipment to analyze samples and control the operation thereof. | 10-02-2008 |
20080233575 | Methods for increasing accuracy of nucleic scid sequencing - The invention provides methods for improving the fidelity of a sequencing-by-synthesis reaction by resequencing at least a portion of a nucleic acid template. | 09-25-2008 |
20080227970 | Methods And Compositions For Sequencing A Nucleic Acid - The invention provides a family of tethered nucleotide analogs useful in sequencing nucleic acids containing a homopolymer region comprising, for example, two or more base repeats, and to sequencing methods using such tethered nucleotide analogs. | 09-18-2008 |
20080219890 | SAMPLE LOADING AND RECOVERY - A apparatus and method for loading a sample into a microfluidic flow cell allows for more precise loading, reduced cross-contamination, and more efficient use of samples to be analyzed. The system for loading a sample into a flow cell includes a flow cell defining a plurality of individually isolated channels through which fluid can flow. The flow cell also defines an inlet port and an outlet port for each of the channels. The system also includes a base that defines a chamber for receiving the flow cell, a cover pivotally attached to the base, and a passive vacuum source for pulling a volume through the flow cell. The method of loading a sample includes inserting the flow cell into the sample loading apparatus, placing a sample in at least one of the wells of the loading block, activating a vacuum source fluidly coupled to the outlet ports to pull the sample into the channel, and optionally aspirating the unused sample from the well. | 09-11-2008 |
20080219888 | Multi-Channel Flow Cells - A multi-channel flow cell can allow for reduced cross-contamination in sample loading and the ability to observe activity within the flow cell once the channels are loaded. A multi-channel flow cell includes a plurality of independently-addressable channels sandwiched between a two substrates. Each of the channels can be coated with a layer that facilitates support-binding of an analyte. Each of the channels terminates on one end in an inlet and on the other end in an outlet. A loading block having inlet ports that match the inlets of the channels can be mated to the inlets of the channels, and an outlet block can be mated to the outlets of the channels. Analytes can be introduced into the channels via the inlet ports of the loading block and are pulled through the channels by capillary action or by vacuum. Once analyte has been introduced into each of the channels, the loading and outlet blocks can be removed and the device turned over. Such a flow cell can be used for streamlining the process of reaction and interrogation of biochemical assays at the microfluidic level. Reagents can be introduced into each of the channels of the flow cell for chemical reactions therein, excess reagent being washed out through the channel outlets. Observation of optically-detectable moieties is then conducted. With such a flow cell optical labels associated with incorporation in a sequencing-by-synthesis reaction can be observed. | 09-11-2008 |
20080213770 | Method of Determining The Nucleotide Sequence of Oligonucleotides and DNA Molecules - The present invention relates to a novel method for analyzing nucleic acid sequences based on real-time detection of DNA polymerase-catalyzed incorporation of each of the four nucleotide bases, supplied individually and serially in a microfluidic system, to a reaction cell containing a template system comprising a DNA fragment of unknown sequence and an oligonucleotide primer. Incorporation of a nucleotide base into the template system can be detected by any of a variety of methods including but not limited to fluorescence and chemiluminescence detection. Alternatively, microcalorimetic detection of the heat generated by the incorporation of a nucleotide into the extending template system using thermopile, thermistor and refractive index measurements can be used to detect extension reactions. | 09-04-2008 |