Disclosed in the present disclosure are a determination system having multiple detection modes and a related method. The determination system having multiple detection modes comprises: a sample stage; an optical module used for scanning a sample under test, the optical module at least having a sequencing mode and a fluorescence staining mode; a driver circuit selectively coupled to mode parameters corresponding to an operation mode of the optical module, the mode parameters at least including a first mode control parameter corresponding to the sequencing mode and a second mode control parameter corresponding to the fluorescence staining mode; and a mode switching circuit coupled to the driver circuit to control the driver circuit on the basis of the sample under test: the mode switching circuit associates different mode parameters with the driver circuit on the basis of the type of the sample under test. The present disclosure achieves multi-mode switching of the detection system, and achieves multiple detection functions on a same platform.
A microfluidic chip, a sample treatment system and a use thereof, and a sample treatment method. The microfluidic chip comprises a sample treatment cavity and a plurality of storage cavities; the sample treatment cavity is used for providing space for sample treatment; the plurality of storage cavities are used for storing samples; the plurality of storage cavities include a first storage cavity, a second storage cavity and a third storage cavity; both the first storage cavity and the second storage cavity can be communicated with the sample treatment cavity, but the first storage cavity and the second storage cavity are not communicated with the sample treatment cavity at the same time, and the third storage cavity is not communicated with the sample treatment cavity; and the third storage cavity is provided with a first interface interacting with a pipetting device. In the present application, by means of the structural design of the microfluidic chip, different samples can be sequentially input into a same sample treatment cavity from different cavities, and multi-step reaction is carried out, reducing sample loss; and a temperature control device involves simpler design and lower cost.
A negative pressure-based adsorption system and method, and a biochemical substance analysis method and device. The adsorption system comprises a gas storage module, a first power module, and a first adsorption module. The first power module is communicated with the gas storage module and is configured to generate negative pressure in the gas storage module. The first adsorption module is configured to be communicated with the gas storage module. The gas storage module is configured to convey negative pressure to the first adsorption module, so that the first adsorption module uses the negative pressure to adsorb a target object.
Optical analysis systems and methods including optical elements positioned on opposite sides of an intermediate imaging plane to create anisotropic distortion associated with a non-linear scanning of an objective relative to a substrate including an analyte array in order to remove motion blurring and produce diffraction limited imaging.
Provided are a multi-template nucleic acid synchronous sequencing method and use thereof. The method includes: providing a plurality of composite nucleic acid template spots, with a plurality of nucleic acid templates being arranged in the plurality of composite nucleic acid template spots; hybridizing the plurality of nucleic acid templates with corresponding sequencing primers thereof; performing, by use of the sequencing primers, a plurality of sequencing reaction cycles on each of the plurality of nucleic acid templates hybridized with the sequencing primers, wherein in each of the plurality of sequencing reaction cycles, signal intensities generated by the plurality of nucleic acid templates exhibit variations from one another; and classifying sequencing channel signals into the plurality of nucleic acid templates based on the variations in the signal intensities for each of the plurality of sequencing reaction cycles.
Provided are a gene sequencing system and method, a device, and a non-volatile storage medium. The system comprises: a control apparatus, a first biochemical reaction and detection platform, and a second biochemical reaction and detection platform, wherein the control apparatus is used for controlling the first biochemical reaction and detection platform and the second biochemical reaction and detection platform to respectively execute synchronous or asynchronous sequencing processes. The technical problems in the related art of large size and long sequencing time of gene sequencing systems due to the need for two platforms to respectively perform biochemical reaction and signal detection on a sequencing slide during gene sequencing are solved.
Provided are a loading method and apparatus, and a computer program product and a sequencing system. The method comprises: a second scheduling apparatus receiving a loading request for a second sample; the second scheduling apparatus determining that a first scheduling apparatus is in a loading and sequencing state, wherein the loading and sequencing state is a state in which a sub-device is called to execute sequencing steps of a corresponding sequencing process node for a first sample; on the basis of the second scheduling apparatus determining that the first scheduling apparatus is in the loading and sequencing state, the second scheduling apparatus determining that the loading sub-device is not an occupied sub-device, wherein the loading sub-device is a sub-device corresponding to at least one sequencing process node executed after the second sample corresponding to the loading request is loaded, and the occupied sub-device is a sub-device currently called by the first scheduling apparatus; and on the basis that the loading sub-device is not an occupied sub-device, the second scheduling apparatus calling the loading sub-device to execute the corresponding sequencing process node for the second sample, so as to complete loading, thus solving the problem of the sample loading modes of a sequencing system being inflexible.
A biological chip and a manufacturing method therefor. The biological chip comprises a chip body, the chip body is provided with a plurality of groove structures having openings on the same side, and the plurality of groove structures include a first groove and at least one second groove which is closest to the first groove and has a different depth. The depths of the most nearest groove structures in the biological chip are different, so that a mutual interference between optical signals generated by samples in the adjacent groove structures can be reduced, thereby improving the resolution of a fluorescent optical system and increasing the signal-to-noise ratio of the biological chip during detection processes. Furthermore, a processing flux can be improved by increasing the density of the groove structures, and signal quality can be improved by controlling the depths of the groove structures, thereby achieving the compatibility of high flux and high signal quality. In addition, the biological chip allows repeated use, thereby effectively reducing the use cost.
Provided are a nucleic acid detection primer combination or kit, a nucleic acid hybridization method, a method for detecting a target nucleic acid, and a method for joint detection of a nucleic acid and a protein. By using the primer combination and the detection method, the incubation time for fluorescence reading/detecting a hybridization signal for a nucleic acid (such as RNA) can be shortened, ensuring that after hybridization of a nucleic acid molecular signal, multiple rounds of protein staining can still be carried out on a sample, i.e. an RNA-protein joint detection method, which provides two types of evidence for staining a target site by means of detection results.
Provided is a hydrogel-based sequencing method suitable for a flowcell sequencing system and also supporting open-source sequencing system, and which can effectively reduce costs while ensuring sequencing efficiency and accuracy.
Provided are an adapter addition method, and a use thereof in the preparation of a high-throughput sequencing library. First, provided is a method for adding an adapter to a blunt-ended double-stranded DNA fragment, comprising: contacting the blunt-ended double-stranded DNA fragment with an enzyme having a terminal transferase activity and/or function and an adapter, wherein the enzyme is used for adding a nucleotide fragment 1 to the 3'-end of each strand of the double-stranded DNA fragment, and the nucleotide fragment 1 is reversely complementary to a nucleotide fragment 2 at the 3'-end of the adapter, so that the adapter is combined with the double-stranded DNA fragment, to obtain a double-stranded DNA fragment to which the adapter has been added. Furthermore, fragmentation, end repair, and adapter addition are carried out in one reaction system, thereby greatly reducing the operation complexity of library preparation. The problems of excessive steps, a high technical use threshold, a low template utilization rate, etc., in high-throughput sequencing library construction are solved.
The present invention relates to a method for acquiring a full-length transcript sequence. The method comprises: performing reverse transcription treatment on the mRNA to be tested; performing second-strand synthesis treatment on a product after the reverse transcription treatment; performing digestion treatment on a product after the second-strand synthesis treatment in the presence of endonuclease, wherein the endonuclease specifically recognizes a nucleic acid fragment with universal bases; performing polymerase chain reaction treatment on a product after the digestion treatment; and performing sequencing treatment on a product after the polymerase chain reaction treatment, so as to obtain a full-length sequence of the mRNA to be tested. The reverse transcription treatment or the second-chain synthesis treatment is performed in the presence of universal bases.
The present invention relates to the technical field of gene detection. Provided are a long-read and short-read co-sequencing device and a bioinformatics sequencing method. The method comprises: performing first base sequencing processing on a test object, so as to obtain a long base sequence of the test object; and performing second base sequencing processing on the test object, so as to obtain at least one short base sequence of the test object; and on the basis of the long base sequence and the at least one short base sequence, determining a target base sequence corresponding to the test object. Obtaining an accurate target base sequence while ensuring the base detection efficiency is achieved on the basis of maintaining the base detection efficiency of the acquiring of the long base sequence in combination with the base information accuracy of the short base sequence, such that the target base sequence can conform to the actual situation of the test object.
The present invention provides an acoustofluidic microfluidic chip and system, and a use thereof. The acoustofluidic microfluidic chip comprises a microporous array chip, a microfluidic channel layer, and a bulk acoustic wave resonator array chip which are sequentially stacked in a thickness direction. The acoustofluidic microfluidic chip of the present invention uses acoustofluidics to manipulate micro-objects such as cells or cell secretions, can realize accurate capture, in-situ cell culture, and selective recovery of the micro-objects, has the advantages of simple structure, low cost, high flux, high integration and the like, and has high application value.
B01L 3/00 - Containers or dishes for laboratory use, e.g. laboratory glasswareDroppers
B81B 7/02 - Microstructural systems containing distinct electrical or optical devices of particular relevance for their function, e.g. microelectro-mechanical systems [MEMS]
C12M 1/00 - Apparatus for enzymology or microbiology
C12M 1/42 - Apparatus for the treatment of microorganisms or enzymes with electrical or wave energy, e.g. magnetism, sonic wave
C12N 5/02 - Propagation of single cells or cells in suspensionMaintenance thereofCulture media therefor
15.
METHOD FOR CULTURING, DETECTING AND SCREENING CELL
The present disclosure relates to the fields of life science and medicine. Specifically, the present disclosure relates to a method for culturing, detecting and screening a cell. A method for capturing a cell secretion comprises: performing culture treatment on a single cell under a suitable condition; and performing controllable rotary flotation treatment on a first affinity reagent in a single cell culture treatment system, wherein the affinity reagent can specifically bind to the secretion of the single cell.
A fluid conveying system and method, and a gene sequencer. The fluid conveying system comprises a fluid storage module, a first working module, and a second working module. The fluid storage module is used for storing a plurality of fluids. The first working module comprises a fluid selection assembly and a first power assembly, and the second working module comprises a second power assembly. At least one of the first working module and the second working module is selectively communicated with a fluid utilization system. The fluid selection assembly is used for selecting one fluid from the fluid storage module, and the power assembly is used for driving the selected fluid to be transferred to the fluid utilization system. The second power assembly is used for driving another fluid in the fluid storage module to be transferred to the fluid utilization system.
This disclosure provides a technology for improving the length and accuracy of sequence reads obtained from a DNA fragment library. Amplicons (such as DNA nanoballs or PCR clusters) are prepared that have longer fragment inserts. This makes the amplicons larger, resulting in lower signal intensity per amplicon, and increasing the likelihood that primer extension products will go out of phase. To compensate, the amplicons are arrayed closer together, and compacted using crosslinking oligonucleotides and a high magnesium concentration. Primer extension products are kept in phase by improving incorporation of bases, ensuring that reactions go to completion, and purging unused reagents. Data collection is improved with brighter detection reagents using a two color four image (2c4i) detection protocol. When these features are combined, accurate reads of 600 to 1000 base pairs or more are routinely obtained.
mlmm). The problem of inaccurate focusing during detection using a gene sequencer that is caused by a mechanical elastic link being prone to causing position oscillation can be overcome.
Provided are a primer, and a use thereof in LAMP amplified product detection. The primer comprises: a single-stranded region comprising a first single-stranded sequence, the first single-stranded sequence having a 3' free end; and a double-stranded region, the 3' end of one complementary strand of the double-stranded region being connected to the 5' end of the first single-stranded sequence.
Systems and methods for synthetic image generation and machine learning analysis for biological substances. In one example, a set of real microscopy images representing objects of a biological substance is received. Each object corresponds to one or more pixels of the real microscopy image. Features of the real microscopy image and the objects are accessed and a set of synthetic microscopy images representing the objects of the biological substance is generated based on the features. In another example, a set of synthetic microscopy images is generated using seed intensities and features extracted or known from a set of real microscopy images. A set of seed images for the synthetic microscopy images is generated from the seed intensities. A trained machine learning model is generated to generate intensity values for additional real microscopy images using the synthetic microscopy images and the seed images as training data.
The present invention relates to the field of sequencing. In particular, the present invention relates to a modified nucleotide as represented by formula (I-1), and a preparation method therefor and the use thereof for sequencing.
Provided are a reagent kit and use thereof in sequencing. The reagent kit includes a first reagent and a second reagent. The first reagent is selected from a disulfide bond reducing agent. The second reagent is selected from a blocking reagent suited to blocking a disulfide bond.
A body fluid sampling apparatus and a body fluid sampling method. The apparatus comprises a puncture module, a driving module, a reset module, and a first locking module. The puncture module comprises a puncture member. The driving module comprises a first actuator with driving potential energy. The first actuator is used for driving the puncture member to penetrate out of a sampling opening of a housing in a first direction from a first position and move to a second position. The reset module comprises a second actuator with reset potential energy. The second actuator is used for driving the puncture member to return to the sampling opening in a reverse direction of the first direction from the second position. The first locking module is used for locking the reset module and unlocking the reset module when the puncture member reaches the second position to enable the second actuator to drive the puncture member to return. The whole process–from the puncture member moving to the second position, to the first locking module unlocking the reset module, and then to the second actuator driving the puncture member to return–is interlinked, thereby facilitating the reduction in the retention time of the puncture member within the barrier.
A61M 5/00 - Devices for bringing media into the body in a subcutaneous, intra-vascular or intramuscular wayAccessories therefor, e.g. filling or cleaning devices, arm rests
A61M 5/20 - Automatic syringes, e.g. with automatically actuated piston rod, with automatic needle injection, filling automatically
Provided in the present disclosure are a base calling method, a base analysis method, and a system, an electronic device and a storage medium. The base calling method comprises: acquiring first light intensity data corresponding to each target pixel point in a target image in a set number of instances of test sequencing, wherein each target pixel point corresponds to one DNB; on the basis of the first light intensity data, determining light intensity distribution intervals respectively corresponding to different types of bases; acquiring target light intensity data corresponding to each target pixel point in the target image in any instance of actual sequencing; and on the basis of the target light intensity data and the light intensity distribution intervals, obtaining a target base calling result in the actual sequencing. In the present disclosure, base calling can be realized by means of distributed computing, such that data transmission pressure and analysis pressure are reduced, storage consumption is reduced, and the occurrence of uneven light emission caused by DNB rolling-circle efficiency is also reduced, thereby effectively improving the accuracy of base calling and the processing efficiency.
A consumable-based biochemical substance analysis device, comprising a housing, a biochip, and a liquid adding apparatus. The housing encloses a sealed reaction chamber; the biochip comprises a biosensing layer and a sensor layer, a sample under test being fixed on the biosensing layer; the liquid adding apparatus is located above the biochip; a reagent is stored in an inkjet chip of the liquid adding apparatus; the inkjet chip is used for loading the reagent to the biochip; a heating cover is used for heating the reaction chamber so that the sample under test reacts with the reagent and generates an optical signal; and the sensor layer is used for collecting the optical signal, and converting the optical signal into a digital signal and outputting same to a client. The present application further provides a biochemical substance analysis method, a disposable base calling apparatus and a sequencing method. In the present application, by achieving a consumable-based design of the biochip, the liquid adding apparatus and the like, and incorporating process control and data processing of a client APP, the entire biochemical substance analysis process can be fully consumable-based, thereby lowering the barrier to sequencing, and reducing fixed investment.
An optical shaping system, an illumination spot shaping method, a sequencer optical system, a sequencing method, and a biological sample optical test method. The optical shaping system comprises: a light source; a first shaping module comprising a plurality of lenses, wherein at least two lenses of the plurality of lenses have the same focal length, the at least two lenses having the same focal length are located between the light source and a field stop (40), and the first shaping module is configured for shaping spots emitted by the light source in a first direction; a second shaping module comprising a plurality of lenses, wherein the plurality of lenses vary in focal length, and the second shaping module is configured for shaping spots emitted by the light source in a second direction; and an objective lens (50), wherein the objective lens (50) is configured for receiving spots which are emitted by the light source and pass through the first shaping module and the second shaping module. The optical shaping system can increase the utilization of light energy.
The present invention belongs to the field of gene sequencing, and particularly relates to a recovery method for a nucleic acid-containing solution used for sequencing on a machine. The method can fully utilize the feature of a high density of a nucleic acid-containing solution used for sequencing on a machine, and the density of the nucleic acid-containing solution will not obviously reduced after one time of use, and therefore a recovered nucleic acid-containing solution still has the capability of being loaded onto flow cells for two times, even three times for sequencing, thus improving the utilization rate of nucleic acid-containing solutions, realizing the purpose of recovery of nucleic acid-containing solutions, and avoiding the labor and material consumption caused by repeatedly preparing nucleic acids (libraries). When being used for sequencing, and if there is a requirement of repeated assays, the present method can directly perform sequencing again without the processes of preparing libraries and nucleic acid-containing solutions, thereby shortening the sequencing process and reducing the preparation time and the sequencing cost of samples. In addition, the present method can avoid insufficient data volumes in sequencing due to excessively small amounts of rare samples, thereby improving the utilization rate of rare samples and further improving the depth of sequencing.
A base calling method and system, an analysis method and system, and an electronic device and a storage medium. The base calling method comprises: acquiring first light intensity data corresponding to each target pixel point in a target image under a set number of instances of test sequencing, wherein each target pixel point corresponds to a nucleic acid sequence cluster to be tested; on the basis of the first light intensity data, determining light intensity distribution intervals respectively corresponding to different types of bases; acquiring target light intensity data corresponding to each target pixel point in the target image under any instance of actual sequencing; and on the basis of the target light intensity data and the light intensity distribution intervals, obtaining a target base calling result under the instance of actual sequencing. Base calling can be implemented by using distributed computing, so that data transmission pressure and analysis pressure are reduced, and storage consumption is reduced; and the occurrence of luminescence unevenness caused by the efficiency of DNB rolling circle amplification is also reduced, thereby effectively improving the accuracy and processing efficiency of base calling.
G16B 40/00 - ICT specially adapted for biostatisticsICT specially adapted for bioinformatics-related machine learning or data mining, e.g. knowledge discovery or pattern finding
G16B 40/10 - Signal processing, e.g. from mass spectrometry [MS] or from PCR
29.
THERMAL SYSTEMS AND METHODS FOR FLOW CELLS, OTHER ANALYTIC SUBSTRATES, AND OTHER MICROFLUIDIC DEVICES
Thermal systems and methods including cooling and heating fixtures for use with flow cells and other analytic substrates. The cooling fixture (200) includes a turbulent air flow cavity (202) with an array of air flow diverters (204) that facilitates fast, accurate, and uniform cooling of a flow cell (100) or other substrate positioned across an opening (206) of the cavity (202). The heating fixture (300) includes an array of light emitting diodes (302) that are spaced apart from and configured to provide overlapping radiation intensity profiles that facilitate fast, accurate, and uniform heating of the flow cell (100) or other substrate positioned relative to the LED array.
Thermal systems and methods including cooling and heating fixtures for use with flow cells and other analytic substrates. The cooling fixture includes a turbulent air flow cavity with an array of air flow diverters that facilitates fast, accurate, and uniform cooling of a flow cell or other substrate positioned across an opening of the cavity. The heating fixture includes an array of light emitting diodes that are spaced apart from and configured to provide overlapping radiation intensity profiles that facilitate fast, accurate, and uniform heating of the flow cell or other substrate positioned relative to the LED array.
A fluid loading module, a fluid loading system, a fluid loading method, and a gene sequencing device. The fluid loading module is configured to load fluid to a solid-phase slide. The solid-phase slide comprises a plurality of openings. The fluid loading system comprises a manifold block and a valve device. A first flow channel is disposed in the manifold block, and a first fluid inlet, a second fluid inlet, a first flow channel outlet and a plurality of slide interfaces are provided on the manifold block, both the first fluid inlet and the first flow channel outlet being connected to the first flow channel. Each slide interface is provided with a first hole, the first hole of each slide interface being connected to one opening of the solid-phase slide. The valve device comprises a plurality of first valves. Each first valve is connected to the first flow channel and the first hole of one slide interface, such that the first fluid inlet is in communication with a corresponding slide interface by means of one first valve. The second fluid inlet is in communication with another slide interface.
Provided are a DNA polymerase mutant and a use thereof. Compared with a wild-type KOD DNA polymerase, the DNA polymerase mutant has amino acid mutations at sites 408 and 409, or at functionally equivalent sites, and amino acid mutations at at least one of the following 23 sites or functionally equivalent sites: site 141, site 143, site 147, site 383, site 384, site 389, site 485, site 584, site 589, site 397, site 424, site 432, site 445, site 523, site 553, site 561, site 564, site 461, site 481, site 605, site 663, site 711, and site 725; an amino acid sequence of the mutant other than the amino acid mutation sites has at least 90% identity with a corresponding amino acid sequence of the wild-type KOD DNA polymerase; and the wild-type KOD DNA polymerase has an amino acid sequence as shown in SEQ ID NO: 2.
The present disclosure relates to the technical field of sequencing, and in particular to a method and reagent for preparing a sequencing library. Provided in the present disclosure is a method for preparing a sequencing library. According to the method, by means of additionally adding an additive or an additive combination capable of reducing the DNA secondary structure and/or reducing the degradation of single-stranded DNA in the single-chain cyclization reaction and/or the rolling circle amplification reaction, and additionally adding an additive or an additive combination capable of reducing the DNA secondary structure and reducing the degradation of single-stranded DNA and/or reducing the stability of the double helix structure of double-stranded DNA in the rolling circle amplification reaction of the double-stranded circular library, the ability of the DNA ligase and/or the strand displacement DNA polymerase to bind to a target nucleic acid is enhanced, such that the non-uniform rolling circle amplification efficiency of different circular DNAs caused by the secondary structure is reduced, the probability that the loose single-stranded DNA is easily degraded is reduced, the amplification uniformity of regions with different GC contents and different sequence characteristics in the library is improved, and thus the sequencing quality and the yield of sequencing data are improved.
A sequencing chip and a preparation method therefor, the preparation method comprising: forming on the surface of a substrate (1) an adsorption layer (2) for adsorbing biological samples; forming an isolation layer (3) on the surface of the adsorption layer (2); and forming a plurality of pore structures (4) in the isolation layer (3), such that the adsorption layer (2) is exposed from the pore structures (4), thus obtaining a sequencing chip. By means of depositing an adsorption layer and an isolation layer on a substrate, forming a pore structure array in the isolation layer, and then using the adsorption layer to adsorb biological samples, the sequencing chip involves a simple process and has pore structures with high dimensional precision, thereby improving the sequencing stability and quality of sequencing chips; physical isolation between samples can be realized, thereby solving the problem of inter-sample signal interference in a high-density sequencing chip; moreover, the sequencing chip can be repeatedly used, thereby saving on costs.
A nucleic acid sequencing method comprises (a) positioning a flow cell in a flow cell imaging system. The flow cell includes a substrate and a coverslip, and the flow cell imaging system includes an optical subsystem including an immersion objective and a compensator assembly configured to selectively apply one of a plurality of pre-determined optical corrections. The acid sequencing method also includes receiving manufacturing variability data about the coverslip positioned in the flow cell imaging system, selectively applying one of the plurality of pre-determined optical corrections to the optical subsystem based on the received manufacturing variability data about the coverslip positioned in the flow cell imaging system.
The present invention relates to a method and device suitable for classification of sparse signal amplification containers. The method comprises: for each of a plurality of amplification containers, performing signal acquisition at a given time point to obtain an original real-time signal data set; on the basis of the original real-time signal data set, performing primary classification on at least one of the plurality of amplification containers to obtain an initially determined amplification container and an initially determined non-amplification container; determining an amplification baseline on the basis of at least some of signals of the initially determined non-amplification container, and using the amplification baseline to correct at least a part of the original real-time signal data set to obtain a corrected real-time signal data set; and on the basis of the corrected real-time signal data set, performing secondary classification on at least one of the plurality of amplification containers to obtain a finally determined amplification container and a finally determined non-amplification container.
Provided in the present application are a nucleic acid amplification product test method, a primer composition and a kit. The primer composition comprises: a first primer group, the first primer group comprising a forward primer and a reverse primer, the first primer group comprising at least one modified primer, and the 5' end of the modified primer being provided with a labeled fluorescent group or a quenching group; and a probe, the probe being adapted to complementarily pair with the 5' end of the modified primer, the 3' end of the probe being provided with a quenching group or a fluorescent group, and the quenching group being adapted to quench the fluorescent group.
A method for rapidly constructing a nucleic acid library, relating to the technical field of library construction. Provided is a reagent combination for DNA end repair-linker ligation. An end-repair enzyme excises a 3' overhang of a DNA fragment and/or fills in a 5' overhang of the DNA fragment to finally form a blunt-ended double-stranded DNA fragment; a ligase ligates the end-repaired DNA fragment with linkers; a nucleic acid extension enzyme extends complementary strands of the linkers ligating the DNA fragment, so as to obtain a DNA fragment with double-stranded linkers on both ends, thereby implementing end repair and linker ligation within a single reaction system, and reducing the steps of A-tailing and purification. By adding linkers to a DNA in a one-step reaction, one-step library construction is achieved.
A DNA polymerase mutant and use thereof in sequencing. The DNA polymerase mutant comprises: compared to a Pyrococcus sp. GB-D DNA polymerase exo-mutant, the DNA polymerase mutant has at least three amino acid mutations at the following four sites or functionally equivalent sites: position 409, position 410, position 411, and position 486; the Pyrococcus sp. GB-D DNA polymerase exo-mutant has the amino acid sequence shown in SEQ ID NO: 1.
Provided in the present application is a wide-field illumination system, comprising: a light source assembly, which is used for emitting first light and second light, which have different wavelengths; an angle adjustment assembly, which comprises a prism located on light paths of the first light and the second light, wherein the prism emits the received first light and second light at different angles; and a light modulation assembly, which comprises a structured light generation element located on the light paths of the first light and the second light, wherein the structured light generation element can modulate the light intensities and phases of the received first light and second light so as to generate structured light, the structured light comprises first diffracted light formed on the basis of the first light and second diffracted light formed on the basis of the second light, and the first light and the second light which are from the prism are incident to the structured light generation element at different incident angles, such that a target diffraction order of the first diffracted light coincides with that of the second diffracted light. Further provided in the present application are a biological sample recognition method and a sequencing device.
The application discloses a flow cell system which includes a flow cell. The flow cell includes a substrate that is configured to support an analyte array, a cover, and an adhesive arrangement spacing the cover from the substrate to define a fluid gap between the substrate and cover. The flow cell also includes an inlet in fluid communication with the fluid gap and an outer perimeter. In one example implementation, fluid enters the flow cell at the inlet, flows through the fluid gap, and exits the flow cell at the outer perimeter between the substrate and the cover, with adhesive gaps in the adhesive arrangement at the outer perimeter of the flow cell allowing fluid to exit from the fluid gap.
A flow cell including a substrate that is configured to support an analyte array, a cover, and an adhesive arrangement spacing the cover from the substrate to define a fluid gap between the substrate and cover. The flow cell also includes an inlet in fluid communication with the fluid gap and an outer perimeter. In one example implementation, fluid enters the flow cell at the inlet, flows through the fluid gap, and exits the flow cell at the outer perimeter between the substrate and the cover; with adhesive gaps in the adhesive arrangement at the outer perimeter of the flow cell allowing fluid to exit from the fluid gap.
01 - Chemical and biological materials for industrial, scientific and agricultural use
09 - Scientific and electric apparatus and instruments
Goods & Services
Diagnostic preparations, other than for medical or
veterinary purposes; diagnostic preparations for research
laboratory use; diagnostic reagents and preparations, except
for medical or veterinary use; biochemical reagents for
non-medical purposes; cell culture reagents for scientific
and research use; biochemical catalysts; biological
preparations, other than for medical or veterinary purposes;
preparations of microorganisms, other than for medical and
veterinary use; chemical preparations for analyses in
laboratories, other than for medical or veterinary purposes;
chemical reagents, other than for medical or veterinary
purposes. Precision measuring apparatus; diagnostic apparatus for
research laboratory use; devices for analyzing genome
information; laboratory devices for detecting genetic
sequences; nucleic acid sequencers used for analyzing
nucleic acids in scientific research; laboratory equipment,
namely, protein sequence analysis apparatus; gene
amplifiers; dna chips; computer software, recorded; optical
apparatus and instruments.
45.
FLUID TRANSFER SYSTEM, FLUID TRANSFER METHOD, AND BIOCHEMICAL SUBSTANCE ANALYSIS SYSTEM
A fluid transfer system, a fluid transfer method, and a biochemical substance analysis system. The fluid transfer system comprises a fluid storage module, a fluid use module, a fluid quantitative driving module, and an air pressure control module. The fluid storage module is configured to store a fluid. The fluid use module is provided with a flow channel, a liquid inlet end of the flow channel is communicated with the fluid storage module, and a liquid outlet end of the flow channel is communicated with the fluid quantitative driving module. The fluid storage module is further communicated with the air pressure control module. The air pressure control module is configured to provide a pressure for the fluid storage module, so as to enable the liquid inlet end of the flow channel to maintain a positive pressure environment. The fluid quantitative driving module is configured to generate a driving force, so as to enable the fluid in the fluid storage module to be quantitatively transferred to the flow channel. The fluid transfer system of the present application has a simple structure and low costs, can reduce the risk of gas evolution in fluid, improves the quality of biochemical reaction, can more flexibly regulate the flow velocity of the fluid, and ensures that the liquid flow rate in the flow channel is consistent each time.
Provided is a probe composition, comprising: a first probe, the first probe comprising a first oligonucleotide strand and a first antibody, wherein the 5' end of the first oligonucleotide strand is linked to the first antibody, and the first antibody has the activity of binding to a predetermined protein; a second probe, the second probe comprising a second oligonucleotide strand and a second antibody, wherein the 5' end of the second oligonucleotide strand is linked to the second antibody, the second antibody has the activity of binding to the predetermined protein, and at least part of the sequence of the 3' end of the first oligonucleotide strand is suitable for reverse complementary pairing with at least part of the sequence of the 3' end of the second oligonucleotide strand; and a third probe, the third probe comprising a third oligonucleotide strand, wherein at least part of the sequence of the 5' end of the third oligonucleotide strand is complementarily paired with at least part of the sequence of the 3' end of the second oligonucleotide strand.
The present disclosure relates to the related technical field of culture appliances, and in particular, to a culture appliance capable of achieving automated culture medium replacement. According to the present disclosure, a bearing seat for placing a culture is added between the cover and bottom of a conventional culture appliance, and the structure of the bearing seat is correspondingly optimized, so that in a first aspect, the sealing tightness for tissue culture can be ensured; in a second aspect, there is no need to manually transplant tissues one by one during culture solution replacement, and thus, the efficiency of the application process can be greatly improved, and the problem of tissue damage in the transplantation process can be solved; in a third aspect, a specific biological material can be selected for subsequent experiments without affecting other biological materials in a culture medium; and in a fourth aspect, the objective of automated culture can be achieved.
A reaction module, a sample preparation system, a sample preparation method, and a biochemical substance analysis system. The sample preparation system comprises a fluid storage module, a fluid distribution module, a fluid driving module and a reaction module, wherein the fluid storage module is used for storing a fluid; the reaction module has a reaction flow channel, and the reaction flow channel is in communication with both the fluid distribution module and the fluid driving module; the fluid driving module is used for generating a pressure gradient, so that the fluid in the fluid storage module is transferred to the reaction flow channel via the fluid distribution module; and the reaction module is used for executing a biochemical reaction of the fluid. In the present application, by means of the collaborative operation of the fluid storage module, the fluid distribution module, the fluid driving module and the reaction module, transfer/mixing and a biochemical reaction of the fluid are performed, thereby implementing one-stop automatic sample preparation. The present application involves a simple process, has high levels of efficiency and a relatively small amount of fluid loss, reduces cost, and has a high biochemical reaction quality.
A wide-field scanning imaging system, comprising: a light source module (11) for emitting light source light; a light modulation module (12) located on the light path of the light source light and comprising a structured light generation element (121) for modulating the light intensity and phase of the light source light to generate structured light and emitting the structured light; a scanning module (13) located on the emergent light path of the structured light and comprising a scanning galvanometer (131) which is rotatable about a first axial direction and a second axial direction perpendicular to the first axial direction to adjust the propagation direction of the structured light, so that the structured light adjusted by the scanning galvanometer (131) traverses a sample to be tested to generate testing light; an imaging module (14) located on the light path of the testing light and comprising a camera (143) for acquiring the testing light; and a controller (15) respectively electrically connected to the scanning module (13) and the imaging module (14) and configured to synchronously output a driving signal to the scanning module (13) and the imaging module (14) so as to synchronize the deflection of the scanning galvanometer (131) with the exposure of the camera (143). An imaging method of the wide-field scanning imaging system, a super-resolution-based sequencer, and a super-resolution-based biological recognition method are provided.
The present disclosure provides a detecting apparatus, system, and method, and belongs to the technical field of detection. The detecting apparatus includes a beam splitting device, a first dichroic mirror, an objective lens, a fluorescence guiding device, and an imaging system including a plurality of imaging devices. The beam splitting device receives and separates an incident light beam of a plurality of different wavelengths that is formed by lasers from the optical fiber, and to form a plurality of excitation lasers corresponding to the plurality of different wavelengths of the incident light beam; the first dichroic mirror receives the plurality of excitation lasers exiting from the beam splitting device and transmits them to the objective lens, and receives a plurality of fluorescence and transmits them to the fluorescence guiding device; the objective lens receives the plurality of excitation lasers and focuses them respectively on a plurality of different areas of a sample to excite fluorescence, and transmits the plurality of fluorescence to the first dichroic mirror; and the fluorescence guiding device receives the plurality of fluorescence transmitted via the first dichroic mirror and guides the plurality of fluorescence to the plurality of imaging devices respectively. The present disclosure makes it possible to reduce the power density of the laser on the sample without increasing the detection duration, solving the problem that the two aspects of “high speed” and “high detection quality and long read length” cannot be better compatible in the related arts.
A fluid transport device, a fluid transport method, and a biochemical substance analysis apparatus. The fluid transport device comprises a chip, a fluid storage assembly and a driving assembly, wherein the driving assembly and the fluid storage assembly are both in communication with the chip; and the driving assembly uses negative-pressure driving to input a fluid in the fluid storage assembly into the chip, uses negative-pressure driving to suck out the fluid, which has been subjected to a reaction, in the chip, and uses positive-pressure driving to discharge the sucked-out fluid into the fluid storage assembly. The fluid transport device of the present application has a high degree of integration. The fluid is located in the device, and does not come into contact with the biochemical substance analysis apparatus during use, thus simplifying the structure of the apparatus, avoiding damage to the apparatus, reducing the cost, reducing the complexity of an experimental process, and increasing the experimental success rate.
A nucleic acid sequencing system may include a substrate including a three-dimensionally patterned surface. The three-dimensionally patterned surface may define nanowells each including a derivitized area for binding to nucleic acid template molecules. The nanowells may be 100 nm in diameter with 350 nm center-to-center spacing. The substrate may including reflective layers and plasmonically enhanced layers for increasing fluorescent signals during nucleic acid sequencing.
An integrated slide, a liquid changing apparatus, and a biochemical substance analysis system and analysis method. The integrated slide comprises a biochip and an ink-jet chip packaged above the biochip, the biochip and the ink-jet chip defining a biochemical reaction chamber; the ink-jet chip is communicated with the biochemical reaction chamber and is capable of adding into the biochemical reaction chamber a reagent needed by a biochemical reaction, or discharging from the biochemical reaction chamber a residual reagent which has undergone a reaction; the biological chip can implement in-situ signal detection. In the present application, the biochemical substance analysis system using the integrated slide can implement an integrated operation of sample addition, biochemical substance analysis and imaging, thereby simplifying the system structure, reducing reagent losses, helping to improve detection efficiency and reducing detection costs.
G01F 1/64 - Measuring the volume flow or mass flow of fluid or fluent solid material wherein the fluid passes through a meter in a continuous flow by using electric or magnetic effects by measuring electrical currents passing through the fluid flowMeasuring the volume flow or mass flow of fluid or fluent solid material wherein the fluid passes through a meter in a continuous flow by using electric or magnetic effects by measuring electrical potential generated by the fluid flow, e.g. by electrochemical, contact, or friction effects
A biochemical substance analysis system, a biochemical substance analysis method, a sequencing system and a sequencing method. The biochemical substance analysis system comprises a biochemical substance analysis platform and a transfer device. The biochemical substance analysis platform comprises a liquid change device, an imaging detection device and at least one biochemical reaction device. The transfer device transfers a test chip between different sites, the sites comprising a reaction site, a liquid change site and an imaging site. The test chip comprises an open-type slide capable of immobilizing a sample to be tested, and the liquid change device is used for adding a liquid to the test chip. The biochemical reaction device is used for enabling the sample in the test chip to react. The imaging detection device is used for executing imaging detection analysis on the test chip which has undergone a reaction. The biochemical substance analysis system provided by the present application can achieve integrated operation of sample adding, biochemical substance analysis and imaging, thus simplifying the system structure, reducing reagent loss, improving test efficiency and reducing test costs.
Described herein are high coverage single tube Long Fragment Read (stLFR) technology which uses performs stLFR on target DNA fragments that have already been amplified before they are co-barcoded, which provides higher amount of DNA for sequencing and increases sequencing coverage. In some embodiments, the high coverage stLFR described in this application uses two rounds of stLFR. In some embodiments, the target DNA fragments are transposed with transposons having particular positional barcodes that can be used to order sequence reads.
Provided is a repeated sequencing method, comprising: on the basis of a first sequencing primer, performing first sequencing on a sample to obtain a first sequencing sequence based on a first sequencing synthetic strand; bringing an elution reagent into contact with the first sequencing synthetic strand so as to remove the first sequencing synthetic strand; on the basis of the first sequencing primer, performing second sequencing on the sample to obtain a second sequencing sequence based on a second sequencing synthetic strand; and comparing the first sequencing sequence with the second sequencing sequence to determine sequence information of the sample.
A biochemical substance analysis system is used to detect biological characteristics of a sample in a flow cell, and includes a detection system, a scheduling system, a biochemical reaction system, and a control system. The scheduling system is used to schedule the flow cell at different sites, including sites in the detection system and sites in the biochemical reaction system. The biochemical reaction system is used to allow the sample to react in the flow cell. The detection system is used to detect a signal from the reacted sample to obtain a signal representing the biological characteristics of the sample. The control system is used to control the detection system, the scheduling system, and the biochemical reaction system to cooperate. The present disclosure improves the automation degree and flux of the biochemical substance analysis.
G01N 21/63 - Systems in which the material investigated is excited whereby it emits light or causes a change in wavelength of the incident light optically excited
Provided in the present invention is a multiplex RT-PCR amplification method. Primers are designed to be completely or partially complementary hairpin structures, so that the 3'-ends of the primers lose the binding and extension capabilities during an RT process; in addition, the 5'-end strands of the primers comprise one or more cleavage sites at which the 5'-end strands are cleaved by a specific cleavage agent, so that during the RT process, the 5'-end strands of the primers are cleaved at the cleavage sites by means of the specific cleavage agent, but the complementary double strands are maintained. During a high-temperature process of PCR, the cleaved 5'-end strands are free so as to release 3'-end strands to serve as primers for target amplification, thereby regaining the capability of binding primers to templates and the extension capability of 3'-ends.
The present invention provides an oligonucleotide combination, comprising specific oligonucleotides and universal primers. A long-chain primer comprising a universal primer sequence and a sequence complementary to the specific oligonucleotides is generated by means of the specific oligonucleotides and the universal primers. The long-chain primer realizes enrichment of a target area and addition of a universal sequence on a product in a PCR process, so that one-step construction of a targeted library is realized.
01 - Chemical and biological materials for industrial, scientific and agricultural use
09 - Scientific and electric apparatus and instruments
Goods & Services
Diagnostic preparations, other than for medical or veterinary purposes; diagnostic preparations for research laboratory use; diagnostic reagents and preparations, except for medical or veterinary use; biochemical reagents used for non-medical purposes; cell culture reagents for scientific and research use; biochemical catalysts; biological preparations for use in cell cultures, other than for medical or veterinary purposes; preparations of microorganisms, other than for medical and veterinary use; chemical preparations for analyses in laboratories, other than for medical or veterinary purposes; chemical reagents, other than for medical or veterinary purposes Diagnostic apparatus for research laboratory use for detecting pathogens; devices for analyzing genome information, namely, laboratory devices for detecting genetic sequences; laboratory devices for detecting genetic sequences; nucleic acid sequencers used for analyzing nucleic acids in scientific research; laboratory equipment, namely, protein sequence analysis apparatus; gene amplifiers, namely, scientific laboratory research instruments for DNA analysis; DNA chips; recorded computer software for managing laboratory information, data, instruments and workflows in the field of genome sequencing; recorded computer software for processing digital images; recorded computer software for use in database management; optical apparatus and instruments, namely, biological microscopes, fluorescence microscopes and spectrometers for laboratory use
62.
USE OF SAPONIN COMPOUND IN NUCLEIC ACID SEQUENCING
The present invention relates to the field of nucleic acid sequencing. In particular, the present invention relates to a scanning reagent containing a saponin compound, a kit containing the scanning reagent and a method for nucleic acid sequencing by means of using the scanning reagent.
C07J 17/00 - Normal steroids containing carbon, hydrogen, halogen, or oxygen, having an oxygen-containing hetero ring not condensed with the cyclopenta[a]hydrophenanthrene skeleton
Provided in the present disclosure are a method and apparatus for performing joint-calling acceleration on high-performance sequencing data, and an electronic device and a storage medium. The method comprises: determining a division mode for genome variation data according to population information of a plurality of samples; dividing the genome variation data according to the division mode, so as to obtain a plurality of variation data segments corresponding to each piece of genome variation data; merging variation data segments, which have the same rank, in the genome variation data, so as to obtain merged variation data; performing population variation detection on each piece of merged variation data, so as to obtain population genome variation data of each piece of merged variation data; and merging the population genome variation data, so as to obtain target population genome variation data of the plurality of samples. Thus, during population variation detection, by means of performing population anomaly detection on a plurality of pieces of local merged data, and merging detection results, the efficiency of acquiring complete population genome variation data can be improved.
The present disclosure relates to a method for analyzing the sequence of a target polynucleotide by polymerizing a nucleotide mixture and a polymerase multiple times to achieve full polymerization, thereby satisfying the requirements of sequencing, and improving read length and accuracy. Further, the present disclosure also relates to a reagent test kit, the reagent test kit being used for analyzing or sequencing polynucleotides.
The present disclosure provides a population variation detection method and apparatus, an electronic device, and a storage medium. The method comprises: according to population information of a plurality of samples, determining a division mode of genome variation data; according to the division mode, dividing the genome variation data to obtain a plurality of variation data fragments corresponding to the genome variation data; combining variation data fragments in the genome variation data having the same ranking to obtain combined variation data; respectively performing population variation detection on the combined variation data to obtain population genome variation data of the combined variation data; and combining the population genome variation data to obtain target population genome variation data of the plurality of samples. Therefore, in the population variation detection process, population variation detection is respectively performed on a plurality pieces of local combined data, and detection results are combined, so that the efficiency of acquiring complete population genome variation data can be improved.
The present invention relates to the field of biological information, and provides an acceleration method and apparatus for genetic testing and an electronic device. The method of the present invention mainly comprises: obtaining a first variation data set and a second variation data set according to a first genetic sample set; and obtaining a variation quality control model according to the second variation data set, and processing the first variation data set according to the variation quality control model to obtain a first variation detection result corresponding to the first variation data set. According to the technical solution of the present application, variation detection data is divided into a first variation data set and a second variation data set by means of temporary interval information, so that processing is directly carried out with respect to intervals during subsequent quality control, thereby achieving the effect accelerating computation. Compared with a mode of dividing data and allocating tasks during quality control in the past, the method reduces testing time consumption, and effectively improves the computational efficiency of population genome analysis.
44 - Medical, veterinary, hygienic and cosmetic services; agriculture, horticulture and forestry services
Goods & Services
Genetic testing apparatus for medical purposes; Apparatus for DNA and RNA testing for medical purposes; Medical apparatus and instruments for use in medical diagnostics for detecting genetic abnormalities and disease; Apparatus for use in medical analysis; Testing apparatus for medical purposes; Diagnostic apparatus for medical purposes used in medical laboratories; Apparatus for the regeneration of stem cells for medical purposes; Blood testing equipment; Medical apparatus and instruments; Sample and library preparation devices for medical diagnosis, testing, and treatment purposes; Analyzers for bacterial identification for medical purposes. Medical screening; Medical analysis services for diagnostic and treatment purposes provided by medical laboratories; Medical assistance; Genetic testing for medical purposes; Medical analysis services for the diagnosis of cancer; Performing diagnosis of diseases; Providing medical information from a web site; Telemedicine services; Medical services; Remote monitoring of medical data for medical diagnosis and treatment; Genetic testing for cancer risk for medical purposes; Genetic testing of animals for diagnostic or treatment purposes.
Medical apparatus and instruments; needles for medical
purposes; blood collection needles; capillary tubes for
blood; apparatus for taking blood; apparatus for taking
blood samples.
69.
METHOD FOR ADJUSTING VOLUME OF NUCLEIC ACID NANOSPHERES AND USE THEREOF
The present invention belongs to the field of nucleic acid sequencing, and specifically relates to a method for adjusting the volume of nucleic acid nanospheres and the use thereof. Provided in the present invention is a method for adjusting the volume of nucleic acid nanospheres. The method comprises performing condensation treatment on nucleic acids (e.g., adding a nucleic acid condensing agent and/or adjusting the pH value to 3-4.5, so that positively charged counter ions are gathered around the nucleic acids, and negative charges on the surface of the nucleic acids are neutralized by cations by mean of an electrostatic combining effect between anions and cations, thereby causing condensation of the nucleic acids during morphology), which can further alter the morphology of the nucleic acid nanospheres, adjust the volume of the nucleic acid nanospheres, and compress the nucleic acid nanospheres. The nucleic acid nanospheres obtained by means of the method (performing condensation treatment on nucleic acid nanospheres) are more compact, smaller in terms of morphology, and more uniform in terms of size. The method can be used for any situation where the volume of nucleic acid nanospheres needs to be adjusted (reduced) (e.g., a loading process of nucleic acid nanospheres (such as DNB), and a sequencing process after loading).
Provided is a DNA polymerase mutant for sequencing. The DNA polymerase mutant comprises: compared with a Pyrococcus abyssi DNA polymerase exo-mutant, at least three amino acid mutations in the following four sites or functionally equivalent sites: position 409, position 410, position 411, and position 486. The Pyrococcus abyssi DNA polymerase exo-mutant has an amino acid sequence as shown in SEQ ID NO: 1.
A method for adjusting the volume of nucleic acid nanoballs. By performing coagulation treatment on a nucleic acid (for example, adding a nucleic acid coagulating agent and/or adjusting the pH value to 3-4.5, so that positively charged counter ions are gathered around the nucleic acid, and negative charges on the surface of the nucleic acid are neutralized by cations by means of electrostatic bonding of anions and cations, thereby enabling the nucleic acid to coagulate), the shape of the nucleic acid nanoballs can be changed, the volume of the nucleic acid nanoballs can be adjusted, and the nucleic acid nanoballs can be compressed. The nucleic acid nanoballs obtained by the method (performing coagulation treatment on the nucleic acid nanoballs) are more compact, smaller in shape, and more uniform in size. The method can be used in any situation where the volume of the nucleic acid nanoballs needs to be adjusted (reduced) (such as the loading process of nucleic acid nanoballs (such as DNBs), and the sequencing process after loading).
C40B 50/18 - Solid phase synthesis, i.e. wherein one or more library building blocks are bound to a solid support during library creationParticular methods of cleavage from the solid support using a particular method of attachment to the solid support
C12Q 1/6806 - Preparing nucleic acids for analysis, e.g. for polymerase chain reaction [PCR] assay
72.
FLUORESCENT DYE, SYNTHESIS THEREFOR AND USE THEREOF
The present invention relates to a dye compound and a use thereof as a fluorescent marker, and also relates to a method for preparing the compound, a nucleotide or oligonucleotide labeled by the compound, and a nucleic acid sequencing method.
Provided is a method for phosphorylation of a nucleic acid at the 3' end and library construction. The library construction method comprises: performing phosphorylation of a nucleic acid fragment at the 3' end; ligating the nucleic acid fragment having phosphorylation at the 3' end to a linker under the action of an RtcB ligase, so as to ligate the 3' end of the nucleic acid fragment to the 5' end of the linker; and amplifying the ligated product, so as to obtain a sequencing library.
The application discloses a flow cell system which includes a flow cell. The flow cell includes a substrate that is configured to support an analyte array, a cover, and an adhesive arrangement spacing the cover from the substate to define a fluid gap between the substrate and cover. The flow cell also includes an inlet in fluid communication with the fluid gap and an outer perimeter. In one example implementation, fluid enters the flow cell at the inlet, flows through the fluid gap, and exits the flow cell at the outer perimeter between the substrate and the cover, with adhesive gaps in the adhesive arrangement at the outer perimeter of the flow cell allowing fluid to exit from the fluid gap.
The application discloses a flow cell system which includes a flow cell. The flow cell includes a substrate that is configured to support an analyte array, a cover, and an adhesive arrangement spacing the cover from the substate to define a fluid gap between the substrate and cover. The flow cell also includes an inlet in fluid communication with the fluid gap and an outer perimeter. In one example implementation, fluid enters the flow cell at the inlet, flows through the fluid gap, and exits the flow cell at the outer perimeter between the substrate and the cover, with adhesive gaps in the adhesive arrangement at the outer perimeter of the flow cell allowing fluid to exit from the fluid gap.
Variable-gap flow cells, and systems and methods using variable-gap flow cells. In one example, the variable-gap flow cell includes a substrate and a cover movably spaced from one another to define a variable fluid gap between them. An actuator may move one of the substrate and cover between a dispensing configuration and a processing configuration. In the dispensing configuration, the substrate and cover are spaced more widely apart such that a volume of reagent dispensed into the fluid gap is substantially less than the volume of the fluid gap. In the processing configuration, the substrate or cover has been moved by the actuator to narrow the fluid gap, such that the dispensed reagent spreads to substantially fill the narrowed fluid gap. In some implementations, variable-gap flow cells enable scaling of the flow cell for larger substrates while minimizing reagent consumption.
The present invention relates to a method for analyzing a sequence of a target polynucleotide. Full polymerization is achieved by means of multiple times of polymerization of a nucleotide mixture and polymerase, and a marker is detected while the polymerization reaction is performed. Furthermore, the present invention relates to a kit, capable of being used for analyzing or sequencing a polynucleotide.
Disclosed in the present invention are a slide and a biochemical analysis device. The slide comprises: a housing, wherein at least one flow channel is provided in the housing, and is provided with a liquid inlet; and a main liquid inlet, which is provided in the housing, wherein liquid inlets of a plurality of flow channels are all in communication with the main liquid inlet. In the present application, after the slide is suctioned to a holder, the slide can be in communication with a liquid inlet of the holder only by means of the main liquid inlet; therefore, only the main liquid inlet and the liquid inlet of the holder need to be sealed, but the liquid inlet of each flow channel does not need to be independently sealed. The sealing effect is effectively guaranteed, the sealing convenience is guaranteed, and the compatibility range of the slide is expanded, that is, slides with different flow channels can adapt to the range of different run data.
A slide glass, a sequencer, and a biochemical analysis apparatus. The slide glass comprises: a shell, wherein at least one flow channel is formed in the shell, and the flow channel is provided with a liquid inlet; and a main liquid inlet formed on the shell, wherein the liquid inlets of a plurality of flow channels are all communicated with the main liquid inlet. After the slide glass is suctioned to a carrier stage, only the main liquid inlet is communicated with the liquid inlet of the carrier stage, and therefore, it is only needed to seal the main liquid inlet and the liquid inlet of the carrier stage, and it is not needed to separately seal the liquid inlet of each flow channel. The sealing effect is effectively guaranteed, the sealing convenience is guaranteed, and the compatibility range of the slide glass is expanded, that is, the slide glasses of different flow channels can adapt to different ranges of the amount of once loaded data.
Embodiments of the invention provide an improved biosensor for biological or chemical analysis. According to embodiments of the invention, backside illumination (BSI) complementary metal-oxide-semiconductor (CMOS) image sensors can be used to effectively analyze and measure fluorescence or chemiluminescence of a sample. This measured value can be used to help identify a sample. Embodiments of the invention also provide methods of manufacturing an improved biosensor for biological or chemical analysis and systems and methods of DNA sequencing.
The present invention relates to the technical field of library construction, and particularly relates to a method for efficiently and quickly constructing a nucleic acid library. The present invention provides an adaptor composition. The adaptor composition can simultaneously attach a 5' end adaptor and a 3' end adaptor to a single-stranded template nucleic acid in a same reaction system by means of the 5' end adaptor, a first ligase, the 3' end adaptor, and a second ligase, without the need to add the 5' end adaptor and the 3' end adaptor in separate steps, thereby greatly reducing the reaction steps and the library construction time, and improving the adaptor attachment efficiency; moreover, the adaptor attachment directionality can be guaranteed, the template nucleic acid loss is reduced, and the utilization rate of original template nucleic acids is increased; no additional fixed sequence is added onto the template, the sequencing quality is not affected, there is no need to perform additional truncation by a certain length of a sequence requiring sequencing, and adaptors will not be attached to each other.
C12P 19/34 - Polynucleotides, e.g. nucleic acids, oligoribonucleotides
C07H 21/00 - Compounds containing two or more mononucleotide units having separate phosphate or polyphosphate groups linked by saccharide radicals of nucleoside groups, e.g. nucleic acids
A nucleic acid tester. The nucleic acid tester comprises: a shell (1) internally provided with an accommodating space, wherein a sample mounting site (16) is arranged in the accommodating space; a control device, which is arranged in the accommodating space; at least one set of optical test assemblies (3), which is arranged in the accommodating space, connected to the control device, and configured to emit test light to the sample mounting site (16) and/or configured to receive excitation light returned by a target in a sample at the sample mounting site (16); and an indication element (4), which is arranged at the shell (1), connected to the control device, and configured to indicate a test result of whether the target is contained in the sample.
G01N 21/78 - Systems in which material is subjected to a chemical reaction, the progress or the result of the reaction being investigated by observing the effect on a chemical indicator producing a change of colour
A sequencing method, and a sequencing method and system. The sequencing method comprises: (1) reacting a target nucleic acid immobilized on the surface of a chip with a polymerization reagent, and incorporating a nucleotide or a nucleotide analog to obtain a reaction product; (2) detecting fluorescent signals; (3) reacting the reaction product with a regeneration reagent to obtain a product that can be used for the next round of polymerization reaction; (4) repeating step (1) to step (3); and continuing in this manner for multiple rounds of cycles to finally obtain sequencing data, wherein the reaction time in at least one of step (1) and step (3) is calculated by a predetermined cycle number-reaction time relationship.
Provides are variant family A polymerases that incorporate 3′-blocked nucleotides into a DNA extension product, a kit comprising such polymerases and methods of using the polymerases in DNA extension reactions, e.g., sequencing reactions.
The methods and compositions disclosed herein relate to preparing libraries to sequence long molecules comprising repetitive regions. In some embodiments, this strategy involves substituting selected nucleotides in each molecule to predetermined, different nucleotides at low frequencies in random positions and co-barcoding the molecule in single-tube LFR reactions to generate mutagenized barcoded fragments. Each mutagenized barcoded fragment comprises a barcode, and the barcode comprises a barcode sequence.
A thermostable strand displacement polymerase and the use thereof in sequencing. Compared with a wild-type Bst DNA polymerase large fragment, the provided mutant Bst DNA polymerase large fragment has more than one mutated amino acid residue. The positions of the mutated amino acid residues relative to the wild-type Bst DNA polymerase large fragment include position 81 and/or position 99 and/or position 321 and/or position 323 and/or position 336 and/or position 400 and/or position 429 and/or position 486 and/or position 488 and/or position 496 and/or position 534 and/or position 547 and/or position 556. The mutant Bst DNA polymerase large fragment has a stable catalytic activity at 65°C, and has a higher strand displacement DNA polymerase activity relative to the wild-type Bst DNA polymerase large fragment.
This application relates to methods and compositions for preparing a library of polynucleotides for sequencing comprises in a single reaction mixture. The method comprises contacting a double-stranded target nucleic acid with one or more nicking agents to produce overlapping nucleic acid fragments separated by staggered single-stranded breaks; and contacting a partially double-stranded first adapter with at least one of the nucleic acid fragments in the presence of a ligase, thereby ligating the 5′ terminus of the double-stranded region of the first adapter to the 3′ terminus of the at least one of the nucleic acid fragments using a DNA ligase via 3′ branch ligation. The first adapter comprises (i) a double-stranded blunt end having a 5′ terminus and a 3′ terminus and (ii) a single-stranded region comprising a barcode.
Provided are a nucleic acid amplification method, a single-stranded multi-copy DNA concatemer and the use thereof. The method comprises: linking a nucleic acid with a known sequence to obtain a nucleic acid to be amplified, and performing an amplification ligation reaction using a primer pair designed on the basis of the known sequence contained in the nucleic acid to be amplified, thereby obtaining a first double-stranded multi-copy DNA concatemer, wherein the two primers of the primer pair can comprise different enzyme cleavage sites 1 and 2 respectively; using an enzyme 1 to cleave the enzyme cleavage site 1 contained in the double-stranded multi-copy DNA concatemer so as to form a single-stranded gap in the double-stranded DNA loop, and using a digestive enzyme to digest the single-stranded gap, so as to obtain a first single-stranded multi-copy DNA concatemer; performing an amplification ligation reaction using a primer with the first single-stranded multi-copy DNA concatemer serving as a template so as to obtain a second double-stranded multi-copy DNA concatemer, using an enzyme 2 to cleave the enzyme cleavage site 2 contained in the second double-stranded multi-copy DNA concatemer so as to form a gap single strand in the second double-stranded multi-copy DNA concatemer, and using the digestive enzyme to digest the gap single strand, so as to obtain a second single-stranded multi-copy DNA concatemer; and using the above-mentioned single-stranded multi-copy DNA concatemer for nucleic acid sequencing .
A gene data encoding method and apparatus, a gene data decoding method and apparatus, and a genetic testing system. A plurality of carrying points are provided on a gene slide, and the carrying points support a sample to be detected having a gene sequence. The encoding method comprises: irradiating a gene slide with excitation light, exciting a sample to be detected so as to generate a fluorescence signal, and generating a reflected light signal at at least one associated position of each carrying point; acquiring the fluorescence signal and the reflected light signal, comparing the fluorescence signal with a first signal threshold and performing encoding according to a comparison result to generate a first identifier, and comparing the reflected light signal with a second signal threshold and generating a second identifier according to a comparison result; and on the basis of the first identifier and the second identifier, generating an encoding sequence associated with a gene sequence. In the process, redundant signal processing is not required, thereby avoiding the large workload of data processing caused by traditional ADC acquisition, making the total amount of data small, saving the storage space, increasing the data utilization rate, and reducing the cost.
42 - Scientific, technological and industrial services, research and design
Goods & Services
Medical laboratory services; genetic testing for scientific
research purposes; structural and functional analysis of
genomes; genetic screening for scientific research purposes;
blood analysis services; DNA screening for scientific
research purposes.
91.
GENE SEQUENCING DEVICE, GENE SEQUENCING METHOD, AND NUCLEIC ACID TEST METHOD
Provided are a gene sequencing device and a gene sequencing method. The gene sequencing device comprises: a biosensing layer comprising one or more sample receiving sites and one or more photosensitive circuits having one-to-one correspondence with the one or more sample receiving sites, wherein the sample receiving sites are configured to receive samples, the photosensitive circuits are configured to receive fluorescent signals emitted by the samples at the corresponding sample receiving sites and to generate analog electrical signals according to the fluorescent signals, and each photosensitive circuit comprises a quantum image sensor; a circuit structure layer, comprising an analog-to-digital conversion circuit configured to convert the analog electric signals into digital electric signals; and a logic processing layer configured to determine the characteristics of the fluorescent signals according to the digital electric signals and to determine the types and/or sequences of bases contained in the samples according to the characteristics of the fluorescent signals.
The present application discloses a leveling control method for a chip, and a related device. The leveling control method comprises: a preparation step: starting a focusing apparatus, and adjusting the distance between the focusing apparatus and a chip such that the focusing apparatus receives an optical signal of a sample to be detected; a detection step: driving the relative movement between the focusing apparatus and a motion platform, such that the focusing apparatus respectively performs focusing on at least three detection points of the chip, and respectively acquiring a focusing adjustment distance between each detection point and the focusing apparatus along the direction of an optical axis of the focusing apparatus; and a leveling step: calculating a deviation angle of the chip on the basis of focusing adjustment distances and the distance between every two detection points respectively, and the motion platform leveling the chip on the basis of the deviation angle. According to the present application, an optical detection platform is automatically leveled and focused by means of the motion platform, thereby reducing the amount of manual labor and improving the efficiency and accuracy.
H01L 21/683 - Apparatus specially adapted for handling semiconductor or electric solid state devices during manufacture or treatment thereofApparatus specially adapted for handling wafers during manufacture or treatment of semiconductor or electric solid state devices or components for supporting or gripping
Provided are a recombinant protein having improved amplification performance, a nucleic acid encoding the recombinant protein, a vector comprising the nucleic acid, a kit comprising the protein, the nucleic acid or the vector, a method for preparing the recombinant protein, and a method for amplifying a target DNA by using the recombinant protein. As a chimeric family A DNA polymerase, the recombinant protein has improved processivity, the amplification performance of the recombinant protein is remarkably better than that of a wild-type family A DNA polymerase, and the thermal stability thereof is higher than that of a family B DNA polymerase.
Embodiments of the disclosure include methods and systems for nucleic acid sequencing that may include an objective coupled to an actuator, wherein the actuator is configured to move the objective over a surface of a substrate. In some embodiments, a droplet may be disposed on the surface of the substrate, and the droplet may be moved along with the objective. The distal end of the objective may include a material that provides a higher friction against the droplet than a material of the surface of the substrate. In some embodiments, the distal end of the objective may be immersed in a fluid as it is moved over the surface of the substrate. The substrate may include vertical walls within a region to retain the fluid.
The present application discloses a liquid path system and a related device thereof, and a cleaning method. The liquid path system comprises: a reagent needle assembly; a cavity structure capable of moving relative to the reagent needle assembly so as to be in contact or non-contact with the reagent needle assembly; a flow cell having one end directly communicated with the internal cavity of the reagent needle assembly or communicated with the internal cavity of the reagent needle assembly by means of a pipeline; and a fluid power member directly communicated with the other end of the flow cell or communicated with the other end of the flow cell by means of a pipeline, wherein the fluid power member is used for delivering a fluid in the flow cell into the cavity structure or delivering a fluid in the cavity structure into the flow cell, and is used for pumping a fluid in a reagent needle into the flow cell when the reagent needle assembly is in non-contact with the cavity structure. According to the present application, the whole liquid path system can be efficiently and thoroughly cleaned.
Disclosed in the present application are a sensing system, a chip package structure, a sequencing slide, and a sequencing method. The sensing system comprises at least two sensing substrates each having a sensing site array, the at least two sensing substrates being spaced apart from each other and stacked. In the stacking direction of the sensing substrates, the sensing site arrays of the two adjacent sensing substrates are arranged opposite to each other and spaced apart from each other so as to form a fluid channel, the sensing site arrays both being exposed to the fluid channel. Each sensing substrate comprises a sensing layer close to the fluid channel and a sensor layer stacked on the side of the sensing layer away from the fluid channel, the sensing site array being arranged on the sensing layer. The sensor layers are provided with sensors for acquiring sensing signals at sensing sites. The sensing system further comprises a signal transmission structure, and the signal transmission structure is electrically connected to the sensor layers of both the two adjacent sensing substrates in the stacking direction, and transmits the sensing signals to the outside of the sensing system.
Provided is a synchronous sequencing method, comprising: constructing a sequencing library for a nucleic acid sample under test; loading the sequencing library to a sequencing chip; performing multiple rounds of synchronous sequencing on the sequencing library, wherein a set of images formed by each round of sequencing reaction is an original image set for synchronous sequencing; on the basis of the original image set for synchronous sequencing, acquiring a base interpretation result of synchronous sequencing; correcting the numerical value of the signal strength of each base channel on the basis of predetermined correction parameters to obtain a corrected base interpretation result; and on the basis of the corrected base interpretation result, determining a base result output by the synchronous sequencing.
The present invention relates to a gene sequencing method and system, and a gene image acquisition method and device. The gene image acquisition method comprises: acquiring a gene image obtained by a camera photographing a sample to be sequenced; determining whether image features of the gene image satisfy a preset feature condition; if no, determining target parameter values of photographing parameters matching a current photographing scene; and triggering the camera to re-photograph said sample according to the target parameter values, such that image features of a re-photographed gene image satisfy the preset feature condition. Therefore, gene images satisfying gene sequencing requirements can be provided for gene sequencing, thereby achieving effective gene sequencing and improving the overall efficiency and accuracy of gene sequencing.
The present invention provides a multi-template nucleic acid synchronous sequencing method and use thereof. The method comprises: providing a plurality of composite template sample points arranged with a plurality of sequencing templates; hybridizing the plurality of sequencing templates with corresponding sequencing primers; conducting, on the basis of the sequencing primers, a plurality of sequencing reaction runs on the plurality of sequencing templates hybridized with the sequencing primers, wherein in each sequencing reaction run, signal intensities produced by the plurality of sequencing templates are different; and classifying the signals of the sequencing channels among the plurality of sequencing templates on the basis of the difference of the signal intensities for each of the plurality of sequencing reaction runs.
The present invention provides a targeted methylation library construction system based on multiplex PCR, a method, and use thereof. The method comprises: a first amplification reaction run 1, wherein the system of the first amplification reaction run 1 comprises: a template DNA and one or more primer pairs, each primer pair comprises a forward primer and a reverse primer, and the 5' end of the forward primer or the reverse primer in each primer pair is provided with a universal sequence 1; and a second amplification reaction run 1, wherein the system of the second amplification reaction run 1 comprises a product of the first amplification reaction run 1 and one or more primer sets, and each primer set comprises: 1) a semi-nested primer 1 with a 3' end linked to one or more target regions in the product of the first amplification reaction run 1 and a 5' end having a universal sequence 2, and 2) a universal primer 1 with a 3' end identical to that of the universal sequence 1 and/or a universal primer 2 with a 3' end identical to that of the universal sequence 2.
C12Q 1/6886 - Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for diseases caused by alterations of genetic material for cancer
