Disclosed is a product and method for sampling cells from a bioreactor, for the purposes of determining the cell count or to remove a sample and retain sterility of the sample for quality control (QC) assessment during a cell expansion in a bioreactor using vacuum tubes in combination with a sampling manifold (1) comprising:a primary fluid conduit (2);a connection port (3) positioned at one end of said fluid conduit (2) comprising means (4) for selective fluid connection of the interior of said fluid conduit (2) to the interior of a sampling reservoir (5); and a plurality of sampling ports (6a-e) disposed along said fluid conduit (2); wherein each of said plurality of sampling ports(6a-e) comprises means (7a-e) for selective fluid connection with an outlet (8a-e) adapted to connect to means (9) to permit exclusively unidirectional fluid flow from said primary fluid conduit.
A bioreactor system includes a vessel having a bottom floor, a flexible bioprocessing bag disposed within the vessel, and a flexible bladder positioned intermediate the bottom floor of the vessel and the bioprocessing bag. The flexible bladder is selectively inflatable to vary at least one of a geometry or configuration of the bioprocessing bag to provide for improved drainability or an increased turndown ratio for the bioreactor system.
Disclosed are bioreactor flasks (10) including a volume extending between a first volume end and a second volume end for the cultivation of cells or other microorganisms, said volume having a horizontal cross section area (CSA) which increases in a direction from the first volume end to the second volume end. The flask optionally includes a housing including a cylindrical lower portion (14) and an inverted truncated conical upper portion (16) which provides said increasing CSA. Disclosed also are arrays of flasks (10), supported in a tray for collective agitation.
A storage vial (100, 200) may include a vial body (110, 210) having a first end (111, 211) and a second end (112, 212) and defining an internal volume (113, 213) configured to contain a biological material (B) therein, a first valve (120, 220) positioned at the first end of the vial body, a second valve (130, 230) positioned at the second end of the vial body, a first conduit connector (160, 260) positioned at the first end of the vial body, and a second conduit connector (170, 270) positioned at the second end of the vial body. The resulting construction may allow for closed system direct transfer of biological material from the storage vial to another vessel using aseptic techniques.
An inflatable bioreactor (110, 210) may include one or more sheets joined to form a bag (111, 211) including a top sheet (118, 218) and a bottom sheet (119, 219) formed from the one or more sheets and being inflatable to provide an internal volume (117, 217) suitable for retaining a volume of culture liquid (10) during flow of the culture liquid resulting from a rocking motion (R) of the bag, and one or more perturbing protrusions (116, 116', 116'', 216) extending upwardly from the bottom sheet toward, but not as far as, the top sheet and extending transversely to, or obliquely to, a direction of wave motion (W) of the culture liquid. The resulting construction may provide improved flow for low initial volumes of the culture liquid in the bag.
The invention relates to a a single-use flexible bioreactor bag comprising a rigid multiport plate sealed to a side wall of said bioreactor bag, wherein said multiport plate comprises a plurality of ports. The invention further relates to a method of manufacturing the bag and to a method of installing the bag in a rigid support vessel.
Disclosed is a microscope stage translation mechanism (100) comprising: a drive (110) rigidly attached or attachable to a bed (105) which drive provides substantially linear motion of a drive element (114); a rocker (130) arranged for pivoting motion about pivot axis (A-A), said axis being stationary relative to said bed (105), the rocker having a first region (122) arranged to be directly engageable with the drive element (114), and a second region (124) distant, relative to the axis, from the first region (122); and a follower having a follower surface (134) arranged to be directly engageable with the second region (124) of the rocker, the follower (130) being attached or attachable to a vertically moveable part of the stage;the mechanism (100) being characterised in that the drive element (114) and the first region (122) have point contact at a first contact point (P) when engaged, and in that the second region (124) and the follower surface (134) also have point contact at a second contact point (P) when engaged.
The present invention relates to a method for purification of viral vectors, more closely it relates to purification of viral vectors from producer cells by using a single automated process. The method comprises the following steps: a) adding producer cells and cell lysis buffer to a processing container; b) mixing said producer cells and cell lysis buffer in said processing container to obtain a mixture; c) flowing said mixture through a chromatography column for purification of viral vectors, wherein the viral vectors are adsorbed on said chromatography column; and d) eluting viral vectors from the chromatography column into a product container.
A probe assembly for inserting a probe into a vessel or tubing includes a probe sheath having a proximal end and a distal end and being configured for operative coupling to a vessel or tubing, the probe sheath being configured to receive a probe and to permit movement of the probe towards the distal end of the probe sheath, and a locking mechanism configured to restrain longitudinal movement of the probe with respect to the sheath in a locked state. The locking mechanism may be unlocked to allow for movement of the probe with respect to the sheath.
This present invention provides means for cell harvesting and isolation to be carried out with a single apparatus. This represents a more convenient way for the processing of cells compared with known methods and represents a useful development for the manufacture of cell therapies.
The present invention relates to a flexible bag, a perfusion filter and a fluid port. The fluid port comprises: - a first fluid connection (3; 3'); - a second fluid connection (5; 5') being in fluid communication with the first fluid connection (3; 3'); - an intermediate fluid path (7: 7') connecting the first fluid connection (3; 3') with the second fluid connection (5; 5'); wherein said intermediate fluid path (7; 7') at least a portion of which comprises a substantially right-angled bend (9; 9'); - a protection cap (11; 11') protecting at least the bend (9; 9') of the intermediate fluid part (7; 7') from contact with other objects; and - a connection surface (13; 13') configured for sealing to a film of an object to be supplied by said port, said connection surface will, when sealed to the film of the object, together with the film provide a fluid tight seal surrounding the first fluid connection (3; 3').
G01M 3/00 - Investigating fluid tightness of structures
C12M 1/00 - Apparatus for enzymology or microbiology
G01M 3/32 - Investigating fluid tightness of structures by using fluid or vacuum by measuring rate of loss or gain of fluid, e.g. by pressure-responsive devices, by flow detectors for containers, e.g. radiators
G01G 17/04 - Apparatus for, or methods of, weighing material of special form or property for weighing fluids, e.g. gases, pastes
A flexible bioprocess bag (1) comprising a number of flexible panels (3a, 3b, 4a, 4b) which are sealed to each other such that when the bag is filled they form at least a bottom (7) of the bag and a side surface (11) of the bag, wherein one of the flexible panels is called a bottom panel (3a) and when the bag is filled said bottom panel (3a) will constitute the bottom (7) of the bag and parts of the side surface (11) of the bag, said parts of the side surface (11) being bent side parts (10a, 10b) of the bottom panel (3a).
The invention discloses a bioreactor 10 for cell culture and expansion, comprising a bioreactor chamber 17, a filter 13 disposed within the chamber 17 and at least one tether 14 loosely tethering the filter to the bioreactor chamber. In an embodiment, the tether(s) allow the filter 13 to move from side to side and/or up and down within the chamber 17, preferably without touching an inner surface of the bioreactor chamber 17. Alternatives show, two, three or four tethers, but one or more tethers can be used.
Disclosed is a hollow fiber filter arrangement (1; 101; 201) and a bioreactor system comprising such a hollow fiber filter arrangement. The hollow fiber filter arrangement comprising: an inlet (3; 103; 203) for receiving a sample to be filtered in the hollow fiber filter arrangement; an outlet (5; 105; 205) for delivering of the filtered sample out from the hollow fiber filter arrangement; a bundle of elongate hollow fibers (7; 107; 207) connected at a first end (9a; 109a; 209a) to the inlet (3; 103; 203) and connected at an opposite second end (9b; 109b; 209b) to the outlet (5; 105; 205); and an outer housing (13; 113; 213) enclosing the bundle (7; 107; 207), wherein a filtrate/waste collection space (15; 115; 215) is provided between the outer housing and the at least one elongated hollow fiber, and wherein the outer housing (13; 113; 213) is made from a flexible material.
/A method of site-specific modification of an endogenous target DNA of a eukaryotic cell is provided. The method includes contacting the endogenous target DNA having an intended modification site with (i) a gene editing system configured to introduce a double strand break in the endogenous target DNA at or near the intended modification site, and (ii) a donor DNA repair template comprising a plurality of tandem repeat sequences. In the method, each of the plurality of tandem repeat sequences comprises an exogenous donor DNA sequence flanked by a donor 5' flanking sequence and a donor 3' flanking sequence. The donor 5' flanking sequence and the donor 5' flanking sequence are homologous to a continuous DNA sequence on either side of the intended modification site in the endogenous target DNA.
A connection clamping device (21; 61; 81; 131; 151) arranged for securing a flexible tube (1) to a barbed end (5b) of a tube connector (5), whereby the barbed end (5b) comprises a barb (9) and the tube connector during connection is arranged to protrude into an end of the flexible tube (1), characterized in that said connection clamping device comprises two sections (23 a, 23b) which, during connection when the tube connector protrudes into an end of the flexible tube, are arranged to be connected and locked to each other by a locking mechanism (33a,33b,34a,34b; 63a, 63b, 64a, 64b) around the tube connector (5) and the flexible tube (1), such that the flexible tube (1) is compressed against the tube connector (5) by a rib (41a, 41b) provided on the inner circumference of the connection clamping device.
F16L 33/23 - Arrangements for connecting hoses to rigid membersRigid hose-connectors, i.e. single members engaging both hoses with means not mentioned in the preceding groups for gripping the hose between inner and outer parts the outer parts being segmented, the segments being pressed against the hose by tangentially arranged members
The invention relates to a method for a computer device, for detecting an optimal candidate compound based on a plurality of samples comprising a cell line and one or more biomarkers, and a plate map configuration, wherein the plate map configuration is providing locations of samples comprising cell lines exposed to one or more biomarkers and different concentrations of a candidate compound forming at least one concentration gradient, the candidate compound being comprised in a plurality of candidate compounds, said method comprising generating (310) phenotypic profiles of each concentration gradient of each of the plurality of candidate compounds at a plurality of successive points in time to form a plurality of compound profiles, wherein generating phenotypic profiles comprises the steps obtaining (312) image data depicting each sample comprised in the concentration gradient, generating (314) a class-labeland a class for each cell of the samples based on the image data,detecting (320) the optimal candidate compound by evaluating a comparison criterion on the plurality of compound profiles. Furthermore,the invention also relates to corresponding computer device, a computer program, and a computer program product.
G06F 19/00 - Digital computing or data processing equipment or methods, specially adapted for specific applications (specially adapted for specific functions G06F 17/00;data processing systems or methods specially adapted for administrative, commercial, financial, managerial, supervisory or forecasting purposes G06Q;healthcare informatics G16H)
G06F 19/18 - for functional genomics or proteomics, e.g. genotype-phenotype associations, linkage disequilibrium, population genetics, binding site identification, mutagenesis, genotyping or genome annotation, protein-protein interactions or protein-nucleic acid interactions
19.
MANUFACTURING SYSTEM FOR BIOPHARMACEUTICAL PRODUCTS
The present disclosure relates to a manufacturing system, method and control circuitry for quality assured manufacturing of at least two biopharmaceutical products. The manufacturing system (100) comprises a warehouse facility (210), a hydration facility (220), and at least two biopharmaceutical manufacturing facilities, wherein the warehouse facility (210) and hydration facility (220) are comprised in the macro structure (200). Each biopharmaceutical manufacturing facility is comprised in a respective micro node (300), and a control facility (230) in the macro structure (200) is configured to control interoperability of the macro structure (200) and the micro nodes (300) by means of a network spine interconnecting the macro structure (200) with each micro node (300).
G05B 19/418 - Total factory control, i.e. centrally controlling a plurality of machines, e.g. direct or distributed numerical control [DNC], flexible manufacturing systems [FMS], integrated manufacturing systems [IMS] or computer integrated manufacturing [CIM]
20.
SELF-CONTAINED SLIDE PROCESSING UNIT FOR BIOLOGICAL SPECIMENS
Systems and methods for processing biological specimens are provided. The biological specimen processing system generally includes a flow cell carrier for holding a microfluidic flow cell and a fluidic handling unit attachable to the flow cell carrier. The fluidic handling unit interfaces with the microfluidic flow cell and can include fluidic pumps, fluidic connections, integrated electronics, and processing software to facilitate processing of a biological specimen contained in the microfluidic flow cell.
Disclosed herein is a cell harvesting instrument suitable for concentrating cells from a source suspension of cells and/or washing said cells, the instrument comprising: a housing for accommodating mechanical elements including at least one fluid pump, at least one valve; and a processing kit removably insertable into the housing, said kit including a generally flat frame having or supporting plural sealed fluid paths arranged in a generally flat plane and such that fluids in the paths do not contact said mechanical elements, wherein at least portions of the fluid paths comprise flexible tubes, the outer surfaces of which are manipulateable by the or each fluid pump, to provide fluid flow in one or more of the paths and /or by the or each valve to restrict fluid flow in one or more of the paths. In an embodiment, the kit comprises also a fluid processing reservoir and a filter suitable for separating cells from fluid in said paths. A transfer mechanism for moving and weighing the fluid processing reservoir is disclosed also.
Disclosed herein is a cell harvesting instrument suitable for concentrating cells from a source suspension of cells and/or washing said cells, the instrument comprising: a housing for accommodating mechanical elements including at least one fluid pump, at least one valve; and a processing kit removably insertable into the housing, said kit including a generally flat frame having or supporting plural sealed fluid paths arranged in a generally flat plane and such that fluids in the paths do not contact said mechanical elements, wherein at least portions of the fluid paths comprise flexible tubes, the outer surfaces of which are manipulateable by the or each fluid pump, to provide fluid flow in one or more of the paths and /or by the or each valve to restrict fluid flow in one or more of the paths.In an embodiment, the kit comprises also a fluid processing reservoir and a filter suitable for separating cells from fluid in said paths. A transfer mechanism for moving and weighing the fluid processing reservoir is disclosed also.
Disclosed herein is an instrument suitable for processing cells for example culturing, concentrating or washing said cells, the instrument comprising: a housing for accommodating mechanical elements including at least one fluid pump; and a disposable processing kit complementary to the mechanical elements within the housing and comprising a fluid circuit including a fluid reservoir and plural fluid paths capable of carrying fluid flow caused by said pump(s), the instrument further including a mechanism for determining the quantity, or change in quantity of the fluid in the reservoir resulting from said fluid flow, the instrument yet further comprising a controller operable to control at least the pump and operable to perform a fault determination process, which includes the steps of determining the expected flow rate of said pump(s) calculated from the speed of the pump(s) and comparing that expected flow with the change in quantity of the fluid in the reservoir as determined by said mechanism.
Disclosed herein is a cell harvesting instrument suitable for concentrating cells from a source suspension of cells and/or washing said cells, the instrument comprising: a housing for accommodating mechanical elements including at least one fluid pump, at least one valve; and a processing kit removably insertable into the housing, said kit including a generally fiat frame having or supporting plural sealed fluid paths arranged in a generally fiat plane and such that fluids in the paths do not contact said mechanical elements, wherein at least portions of the fluid paths comprise flexible tubes, the outer surfaces of which are manipulateable by the or each fluid pump, to provide fluid flow in one or more of the paths and /or by the or each valve to restrict fluid flow in one or more of the paths. In an embodiment, the kit comprises also a fluid processing reservoir and a filter suitable for separating cells from fluid in said paths. A transfer mechanism for moving and weighing the fluid processing reservoir is disclosed also.
C12M 1/00 - Apparatus for enzymology or microbiology
F16K 7/06 - Diaphragm cut-off apparatus, e.g. with a member deformed, but not moved bodily, to close the passage with tubular diaphragm constrictable by external radial force by means of a screw-spindle, cam, or other mechanical means
A61M 39/28 - Clamping means for squeezing flexible tubes, e.g. roller clamps
F16K 7/04 - Diaphragm cut-off apparatus, e.g. with a member deformed, but not moved bodily, to close the passage with tubular diaphragm constrictable by external radial force
C12M 1/34 - Measuring or testing with condition measuring or sensing means, e.g. colony counters
25.
IMPROVEMENTS IN AND RELATING TO CELL HARVESTING APPARATUS
Disclosed herein is a cell harvesting instrument suitable for concentrating cells from a source suspension of cells and/or washing said cells, the instrument comprising: a housing for accommodating mechanical elements including at least one fluid pump, at least one valve; and a processing kit removably insertable into the housing, said kit including a generally flat frame having or supporting plural sealed fluid paths arranged in a generally flat plane and such that fluids in the paths do not contact said mechanical elements, wherein at least portions of the fluid paths comprise flexible tubes, the outer surfaces of which are manipulateable by the or each fluid pump, to provide fluid flow in one or more of the paths and/or by the or each valve to restrict fluid flow in one or more of the paths.In an embodiment, the kit comprises also a fluid processing reservoir and a filter suitable for separating cells from fluid in said paths. A transfer mechanism for moving and weighing the fluid processing reservoir is disclosed also.
A bioreactor system and packaging is provided. The bioreactor system includes a vessel for housing biomaterials for processing and a support structure. The vessel includes a flexible material defining a chamber and a mixing system positioned within the chamber. The mixing system includes an agitator for imparting motion and mixing to the contents of the vessel and includes a base affixed to the flexible material at a base section of the chamber, a shaft moveably mounted in the base and extending from the base into the chamber and at least one mixing element mounted to the shaft, the shaft configured to be driven by a motor magnetically coupled to the shaft and external to the lower portion of the chamber. The support structure is connected to the mixing system such that the shaft is moveable therein and configured to cooperate with an external structure to provide support for the shaft.
A connection clamping device (21; 61; 81; 131; 151) arranged for connecting a flexible tube (1) to a barbed end (5b) of a connection means (5), whereby the barbed end (5b) comprises a barb (9) and the connection means during connection is arranged to protrude into an end of the flexible tube (1), characterized in that said connection clamping device comprises two halves (23 a, 23b) which, during connection when the connection means protrudes into an end of the flexible tube, are arranged to be connected and locked to each other by a locking mechanism (33a,33b,34a,34b; 63a, 63b, 64a, 64b) around the connection means (5) and the flexible tube (1), such that the flexible tube (1) is compressed against the connection means (5) by a rib (41a, 41b) provided on the inner circumference of the connection clamping device.
F16L 33/23 - Arrangements for connecting hoses to rigid membersRigid hose-connectors, i.e. single members engaging both hoses with means not mentioned in the preceding groups for gripping the hose between inner and outer parts the outer parts being segmented, the segments being pressed against the hose by tangentially arranged members
A61M 39/12 - Tube connectors or tube couplings for joining a flexible tube to a rigid attachment
28.
PASSIVE AUTOMATIC ANTIFOAM DELIVERY SYSTEM FOR USE WITH SINGLE-USE BIOREACTORS
The aspects of the disclosed embodiments generally relate to an apparatus which allows for the controlled addition of antifoam to the foam present in the headspace of a disposable single-use bioreactor in a reliable manner. The aspects of the disclosed embodiments also generally relate toa method of using such apparatus which allows for the controlled addition of antifoam to the foam present in the headspace of a disposable single-use bioreactor in a reliable manner. The aspects of the disclosed embodiments generally relate to antifoam systems, methods and apparatus, and more particularly, to an antifoam device operably connected to a single use biobag.
The invention discloses a bioreactor apparatus (1;101;201;301) for cultivation of cells comprising: a) a disposable bioreactor vessel (2) with one or more walls (3,4,5) defining an inner volume (6), at least one port (10) in a wall, wherein the disposable bioreactor vessel is positioned in a rigid support structure (8;108); and b) a heater (9;109;209;309), capable of heating an amount of culture medium to a target temperature in the range of 55-95 ºC, while the amount of culture medium is being confined in or conveyed to the inner volume.
A bioprocess mixer (1), which comprises: - a support vessel (2) with at least one side wall (3, 4, 5, 6) and a bottom wall (7), where the walls define a support vessel inner volume (8), and at least a first (9) and a second (10) magnetic impeller drive unit; and - a flexible bag (11, 111) adapted to fit inside the support vessel inner volume, where the bag has at least one bag side wall (12, 112, 13, 113, 14, 15), a bag bottom wall (16, 116) and a bag top wall (17, 117) defining a bag inner volume (18), and at least a first (19) and a second (20) magnetic impeller rotatably attached to a bag wall in the bag inner volume.
The present invention provides improved methods, facilities and systems for parallel processing of biological cellular samples in an efficient and scalable manner. The invention enables parallel processing of biological cellular samples, such as patient samples, in a space and time efficient fashion. Process simulation may be used to determine the optimal arrangement and/or quantity of cell processing equipment needed. The methods, facilities and systems of the invention find particular utility in processing patient samples for use in cell therapy.
G06F 19/00 - Digital computing or data processing equipment or methods, specially adapted for specific applications (specially adapted for specific functions G06F 17/00;data processing systems or methods specially adapted for administrative, commercial, financial, managerial, supervisory or forecasting purposes G06Q;healthcare informatics G16H)
32.
SHAFT-MOUNTED FLUID TRANSFER ASSEMBLY FOR A DISPOSABLE BIOREACTOR
A fluid transfer assembly for single use bioreactors includes a fluid transfer housing that can be mounted to the impeller shaft using a bearing that places the fluid transfer assembly directly below the lowest impeller but allows the impeller shaft to spin inside independently of the fluid transfer assembly. A fluid conduit connects the fluid transfer housing to a port in the single use bag wall which allows fluids to be introduced into the sparger and which also helps prevent the fluid transfer assembly from rotating with the impeller shaft.
Disclosed is an optical arrangement providing selective plane illumination, including an inverted illumination objective mounted below a sample support in use providing a line or plane of light at the sample support, and at least one image collection objective mounted above the support, said inverted illumination objective having an illumination objective optic axis, and said image collection objective having an image collection objective optical axis, wherein illumination light is arranged to propagate toward the illumination objective lateral offset to the illumination objective optical axis such that the illumination light leaving the illumination objective propagates toward the sample support at an oblique angle relative to the illumination objective optical axis, and wherein the image objective optical axis has an angle α which is obtuse to the illumination objective optical axis and generally perpendicular to light propagating at the sample support.
A product and method for sampling cells from a bioreactor, for the purposes of determine the cell count or to remove a sample and retain sterility of the sample for quality control (OC) assessment. More specifically, a product and a method for sampling of cells during a cell expansion in a bioreactor using vacuum tubes.
A method is provided for generating single-stranded DNA circles from a biological sample. The method comprises the steps of: treating the biological sample with an extractant to release nucleic acids, thereby forming a sample mixture; neutralizing the extractant; denaturing the released nucleic acids to generate single-stranded nucleic acids; and contacting the single-stranded nucleic acids with a ligase that is capable of template-independent, intramolecular ligation of single-stranded DNA to generate the single-stranded DNA circles. All the steps of the method are performed without any intermediate nucleic acid isolation or nucleic acid purification. The single-stranded DNA circles may be amplified and further analyzed. Also provided is a kit which comprises compositions for carrying out the novel methods.
The present invention provides a system for the insertion of a pre-sterilized sensor probe into a sterile vessel. The system of the invention provides a reliable and straightforward way to insert one or more sterile probes into a sterile vessel. The present invention also provides a sterile vessel that includes one or more of the systems of the invention. The sterile vessel can be a flexible or semi-rigid bag or tubing of the type typically used for carrying out biochemical and/or biological processes and/or manipulating liquids and other products of such processes. Furthermore, the present invention provides a method for aseptically inserting a probe into a sterile vessel where the method makes use of the system of the invention.
The present invention provides improved methods, facilities and systems for parallel processing of biological cellular samples in an efficient and scalable manner. The invention enables parallel processing of biological cellular samples, such as patient samples, in a space and time efficient fashion. The methods, facilities and systems of the invention find particular utility in processing patient samples for use in cell therapy.
The present invention provides improved methods for maintaining the physical separation and identity integrity of a biological cellular sample from a patient during processing. The invention enables parallel processing of biological cellular samples, such as patient samples, in a space and time efficient fashion. The methods of the invention find particular utility in processing patient samples for use in cell therapy.
G06F 19/00 - Digital computing or data processing equipment or methods, specially adapted for specific applications (specially adapted for specific functions G06F 17/00;data processing systems or methods specially adapted for administrative, commercial, financial, managerial, supervisory or forecasting purposes G06Q;healthcare informatics G16H)
B01L 3/00 - Containers or dishes for laboratory use, e.g. laboratory glasswareDroppers
G06Q 50/24 - Patient record management (processing of medical or biological data for scientific purposes G06F 19/00)
39.
IMPROVEMENTS IN AND RELATING TO CELL CULTURE MICROSCOPY SLIDES
Disclosed is a cell culture microscopy slide comprising an optically transparent generally flat supporting surface (20) including upper and lower opposed substrate surfaces (27,28). A peripheral frame (40) surrounds the substrate (20), the frame (40) having a lower frame surface (44) and an upper frame surface (42). The lower frame surface (44) and the lower substrate surface (28) are generally flush. The upper frame surface (42) lies above the upper substrate surface (27), to form a well (32), and the upper and lower frame surfaces (42,44) are continuously flat and generally parallel. The substrate is preferably glass having a thickness of 1.7mm.
A flexible bag and a method for filling a flexible bag which is collapsed when empty, wherein at least one fastening means (41a, 41b, 42a, 42b; 43) is provided on a surface of the flexible bag such that at least two upper parts (53a, 53b) of the flexible bag can be held together by this at least one fastening means during a first part of filling of the flexible bag, whereby the fastening means is designed to release when the bag is filled to a certain amount such that the two upper parts being held together by the fastening means will lose contact.
The invention relates to a method for analyzing a target nucleic acid fragment, comprising generating a first strand using one strand of the target as a template by primer extension, using a first oligonucleotide primer which comprises, from 5' to 3', an overhang adaptor region, a primer ID region and a target specific sequence region complementary to one end of the target fragment; optionally removing non-incorporated primers; amplifying the target from the generated first strand to produce an amplification product; and detecting the amplification product. Also disclosed are unique primers useful for such target analysis methods.
C12Q 1/58 - Measuring or testing processes involving enzymes, nucleic acids or microorganismsCompositions thereforProcesses of preparing such compositions involving urea or urease
C12P 19/34 - Polynucleotides, e.g. nucleic acids, oligoribonucleotides
The invention discloses an apparatus (1;11;31) for cell cultivation, comprising a bioreactor (2;12;32), an acoustic standing wave cell separator (5;15;35) and a filter (7;17;37), wherein an outlet (3;13;33) of the bioreactor is fluidically connected to an inlet (4;14;34) of the acoustic standing wave cell separator and a media outlet (6;16;36) of the acoustic standing wave cell separator is fluidically connected to the filter (7;17;37).
B01D 15/02 - Separating processes involving the treatment of liquids with solid sorbentsApparatus therefor with moving adsorbents
B01D 15/08 - Selective adsorption, e.g. chromatography
B01J 19/10 - Processes employing the direct application of electric or wave energy, or particle radiationApparatus therefor employing sonic or ultrasonic vibrations
C07K 1/22 - Affinity chromatography or related techniques based upon selective absorption processes
C12M 1/12 - Apparatus for enzymology or microbiology with sterilisation, filtration, or dialysis means
Objective lens changer (104) comprising: a changer frame (130) arranged to be positioned with respect to the optical path of an optical apparatus, an objective lens carrier (135) moveably attached to the frame by a mechanical link arrangement (140), the objective lens carrier comprising at least two objective lens positions (145) that can be selectively positioned in the optical path by the mechanical link arrangement, wherein the mechanical link arrangement comprises a first link section (150) to provide translation of the objective lens carrier between the objective lens positions and a second link section (155) spaced apart from the first link section in the direction of the optical axis, and arranged to control the alignment of the objective lens position positioned in the optical path with respect to the optical axis, and wherein the mechanical link arrangement is arranged to move the objective lens carrier in one plane and so that the translation between the objective lens positions involves both an angular movement and a linear movement of the objective lens carrier with respect to the optical axis.
The present invention relates to a disposable container (100) comprising a side wall (2, 32), top (4) and bottom (6), wherein the side wall (2; 32) and the bottom (6) comprise a flexible material, wherein the side wall (2; 32), top (4) and bottom (6) are joined together to define the container (100) with an interior compartment (10) for keeping a fluid inside the container (100). The bottom (6)of the container (100)comprises at least one portion of rigid or semi-rigid material comprising a folding means (124; 224; 324; 324') that enables folding of the bottom (6).Thus an easy way of folding the bottom of the container is provided.
C12M 1/00 - Apparatus for enzymology or microbiology
B65D 6/16 - Containers having bodies formed by interconnecting or uniting two or more rigid, or substantially rigid, components made wholly or mainly of metal, plastics, wood or substitutes therefor collapsible
45.
TEMPERATURE CONTROLLING SURFACES AND SUPPORT STRUCTURES
A heat exchange module for use in a chemical, pharmaceutical or biological reactor system can include a body configured to be disposed in the reactor system having an inner replaceable reactant container is disclosed. The body can further include at least one thermally conductive surface adapted to contact the inner replaceable reactant container to facilitate heat transfer. Furthermore, the heat exchange module can include a heat exchanger disposed within the module body and can include a fluid circulation path through which a heat exchange fluid can be circulated.
F28F 7/02 - Blocks traversed by passages for heat-exchange media
B01J 19/00 - Chemical, physical or physico-chemical processes in generalTheir relevant apparatus
B01J 19/18 - Stationary reactors having moving elements inside
C12M 1/00 - Apparatus for enzymology or microbiology
C12M 1/02 - Apparatus for enzymology or microbiology with agitation meansApparatus for enzymology or microbiology with heat exchange means
F28D 1/06 - Heat-exchange apparatus having stationary conduit assemblies for one heat-exchange medium only, the media being in contact with different sides of the conduit wall, in which the other heat-exchange medium is a large body of fluid, e.g. domestic or motor car radiators with the heat-exchange conduits forming part of, or being attached to, the tank containing the body of fluid
46.
METHODS FOR RESOLVING POSITIONS IN FLUORESCENCE STOCHASTIC MICROSCOPY USING THREE-DIMENSIONAL STRUCTURED ILLUMINATION.
Methods and systems to resolve positions of sample components in fluorescence stochastic microscopy using three-dimensional structured illumination microscopy ("3D-SIM") are disclosed. In one aspect, components of a sample specimen are labeled with fluorophores and weakly illuminated with a frequency of light to stochastically convert a subset of the fluorophores into an active state. The sample is then illuminated with a three-dimensional structured illumination pattern ("3D-SIP") of excitation light that causes the activated fluorophores to fluoresce. As the 3D-SIP is incrementally moved within the volume of the sample and images are recorded, computational methods are used to process the images to locate and refine the locations of the activated fluorophores thereby generating a super-resolution image of sample components.
Disclosed herein is a single use, controlled environment manufacturing module in the form of a sterile sealed bag formed of a substantially flexible material, such that the bag can be inflated and deflated for transport and/or disposal. The flexible bag has one or more access ports and connectors to accommodate a variety of biochemical or pharmaceutical manufacturing processes to be carried out within the flexible bag. The interiors of one or more disclosed modules can be connected, forming a module train.
Methods, apparatus, systems and articles of manufacture are disclosed herein to implement flexible bioreactor control systems. An example apparatus disclosed herein includes a processor coupled to a memory, the processor programmed to determine whether the map value included in the process task object is a valid map value, the process task object to correspond to a task executed by a bioreactor, a control device or a measurement device of the bioreactor control system configuration, in response to determining the map value is a valid map value, decode the map value to identify the source location of a first input of the process task object, pull a value from the source location to update the input value of the process task object, and facilitate execution of the process task with the input value.
G05B 13/02 - Adaptive control systems, i.e. systems automatically adjusting themselves to have a performance which is optimum according to some preassigned criterion electric
Disclosed herein is provided a virus purification and formulation process for purifying a flavivirus represented by one of a a Yellow Fever Virus, Japanese Encephalitis virus, Dengue virus, and West Nile virus. The highly purified flavivirus virus product is characterized as having a low level of sucrose without significant virus loss such as that which is typically encountered by prior art virus purification processes. The disclosed process captures and purifies the virus, separating it from the host cell proteins and DNA, and leaving the host cell proteins and DNA behind. The process also can be used to inactivate and/or concentrate the virus sufficiently for use in formulations.
Disclosed herein are embodiments of a valve assembly for preventing dead leg spaces in a container or tubing, the embodiments including a three-way valve system for controlling back-pressure in a fluid generating device, such as a single-use high pressure bioreactor. Also disclosed is a pressurized reactor system for bioprocessing, comprising a single-use container including a flexible wall or a semi-rigid wall.
Disclosed is a heat exchange module for use in a chemical, pharmaceutical or biological reactor system, the module configured to be disposed in the reactor system having a flexible single use container, and including at least one thermally conductive surface adapted to contact the flexible single use container to facilitate heat transfer, and a fluid circulation path through which a heat exchange fluid can be circulated.
Illumination system for a microscope system capable of being mode-switchable between a first and a second illumination mode, comprising one source of light for providing a collimated beam of light, at least one selector mirrorcapable of being positioned in at least two positions to redirect the beam of light in two different beam paths, the first beam path being a direct exit beam path wherein the selector mirror redirects the beam of light along an exit beam path to provide afirst illumination mode, the second beam path is a mirror loop path comprising two or more mirrors arranged to redirect the beam of light onto the selector mirror such that it is redirected by the selector mirror a second time along the exit beam path, and wherein mirror loop path comprises at least one optical element arranged to optically alter the beam of light to provide the second illumination mode. According to one embodiment,the first illumination mode is Total Internal Reflection (TIRF)and the second illumination mode is Photokinetics(PK) illumination.
The current application is directed to autofocus subsystems within optical instruments that continuously monitor the focus of the optical instruments and adjust distances within the optical instrument along the optical axis in order to maintain a precise and stable optical-instrument focus at a particular point or surface on, within, or near a sample. Certain autofocus implementations operate asynchronously with respect to operation of other components and subsystems of the optical instrument in which they are embedded. The described autofocus subsystems employ multiple calibration curves to precisely adjust the z-position of an optical instrument.
G02B 21/16 - Microscopes adapted for ultraviolet illumination
G02B 7/09 - Mountings, adjusting means, or light-tight connections, for optical elements for lenses with mechanism for focusing or varying magnification adapted for automatic focusing or varying magnification
G03B 3/02 - Focusing arrangements of general interest for cameras, projectors or printers moving lens along baseboard
54.
FLUORESCENCE MICROSCOPES WITH POLYCHROIC MIRROR CHANGERS
Fluorescence microscopy systems with polychroic mirror changers are described. In one aspect, a polychroic mirror changer includes a polychroic-mirror array. The array includes a plate with a planar surface and a number of holes formed in the plate. The array also includes polychroic mirrors attachedto the planar surface of the platesuch that each polychroic mirror covers one of the holes and the reflective surface of each polychroic mirror is adjacent to and aligned with the planar surface of the plate. Each polychroic mirror is partially exposed through a corresponding hole to reflect a different subsetof excitation channels of a beam of excitation light input to the changer. The polychroic-mirror array can be mounted in the changer so that when a different subsetof excitation channels is selected to illuminate a specimen, the plate is moved within a single plane of motion.
Microscopy instruments with detectors located on one side of the instruments are disclosed. The microscopy instruments include a splitting system and an array of detectors disposed on one side of the instrument. A beam composed of two or more separate emission channels is separated by the splitting system into two or more beams that travel along separate paths so that each beam reaches a different detector in the array of detectors. Each beam is a different emission channel and the beams are substantially parallel.
Microscopy system for biological imaging, comprising an image quality monitoring system for monitoring image quality of an image of a biological sample comprising a biological object selection means arranged to let a user of the system to select one or more Biological Reference Objects (BRO) in the image of the biological sample, and an image quality evaluation means arranged to compare the signal level of image pixels of the one or more BROs with an image background signal level to calculate one or more image quality parameters for the image of the biological sample. The system is arranged to present the image quality parameters to the user as an indication of the image quality specific for the BRO(s).
Microscopy system for biological imaging, comprising an image quality optimizer for optimizing image quality of an image of a biological sample, allowing a user to select an optimization mode from a list of functionally defined optimization modes, and wherein the system is arranged to automatically set one or more image acquisition parameters to achieve optimal imaging for the selected optimization mode based on at least one image quality parameter derived from one or more Biological Reference Objects (BRO) in the image of the biological sample selected by the user or automatically by the system.
The present invention relates to a system and method for reducing image artifacts for a CMOS camera used as an optical detector for a line confocal fluorescent imager. The method for reducing image artifacts in a monochromatic image comprises subtracting RGB channel offset mismatch; and correcting random row offset for each row. Preferably, the method also comprises correcting random column offset and gain. Optionally, the method also comprises clipping of defective pixels, and/or subtracting dark current. When the monochromatic image is a fluorescence image, the method also comprises a step of compressing CMOS camera noise. Also provided are a system for reducing image artifacts in a monochromatic image from a CMOS camera, as well as an image artifact reduction system for a CMOS camera-based line confocal fluorescent microscope.
A confocal fluorescence lifetime imaging (FLIM) system comprising a pulsed tuneable excitation light source arranged to provide excitation radiation to an illumination area on a target, scanning means for scanning the illumination area across the target, and at least one detector for detecting fluorescent emission from the target, wherein the pulsed light source comprises a line forming unit arranged to form a line shaped illumination area of pulsed excitation light on the target, and wherein the detector comprises shutter means arranged to operate in synchronization with the pulsed light source enabling detection of time-resolved fluorescent emission intensity from the target.
A line confocal microscope system, comprising a scanning unit in the form of a mechanically driven scanning unit with a controllable a scanning trajectory and a two dimensional sensor unit operated in a rolling line shutter mode in synchronization with the scanning unit, wherein the scanning trajectory is set to have an acceleration part outside the field of view of the sensor unit.
A motorized apparatus to simultaneously excise, retrieve, temporarily store and transport a sample of material has a hollow clamshell casing with a blended contoured grip for the fingers, a horizontal extension to eliminate slippage when held in a user's hand, and a flange bottom portion from which a removable cutting tool threaded to a drive shaft extends downwards. Within the clamshell casing an electric motor is mounted which drives, via gears, a drive shaft which rotates a cutting tool threaded to the distal end of the drive shaft. The end of the cutting tool, distal from the clamshell casing, forms a cutting edge circumscribing a circular region. An ejection rod slides reciprocally within the cutting tool between a stowed position and an expulsion position. Users core a sample from the source material by engaging contact between the cutting edge of the cutting tool and the surface of the source material, applying pressure against the surface of the source material while simultaneously activating the motor to rotate the cutting tool. The cutting region of the cutting tool passes through the source material contacting the support surface below the source material which urges the cored sample into the lumen of the cutting tool. The sample may be stored in the lumen or transported. Activation of the ejection rod moves from the stowed position towards the expulsion position displacing the temporarily stored sample from the lumen space in the cutting tool into the appropriate collection receptacle or onto a desired surface.
The present invention relates to a method for providing a sterile connected device, especially of sensitive material, such as material not compatible with sterilization by gamma irradiation. The method comprises providing connectors and a tubing in an autoclave bag, and autoclaving the sealed autoclave bag containing the connectors and tubing for sterilization. Optionally, the connectors and tubing are assembled prior to autoclave. Also provided are sterile, connected devices sterilized according to the present method.
The present invention relates to improvements of bioreactor bags for cell cultivation. The invention provides an inflatable bioreactor bag for cell cultivation comprised of a top and a bottom sheet of polymer material that are joined along their edges to form a sealed bag, wherein two opposing edges are formed as clamping edges to allow clamping of the bioreactor bag to a rocker type bioreactor, wherein the top sheet is at least 5% longer than the bottom sheet between the clamping edges. The bioreactor bags provided by the invention avoid formation of undesired wrinkles or creases which otherwise may lead to fatigue of the plastic and eventually fracture.
The present invention relates to improved single-use bioreactors comprising disposable plastic bags for cell cultivation. The invention provides an inflatable bioreactor bag for cell cultivation comprised of a top and a bottom sheet of polymer material that are joined along their edges to form a sealed bag, wherein two opposing edges are formed as clamping edges to allow clamping of the bioreactor bag to a rocker type bioreactor, and wherein the bioreactor bag is provided with a wrinkle preventing structure at each end of the clamping edges. The bag avoids formation of undesired wrinkles or creases which otherwise lead to fatigue of the plastic and eventually fracture.
A separation system comprises (i) at least two separation units, each separation unit comprising a fluid inlet and a fluid outlet, wherein the separation units are connected in series outlet to inlet to form a line of separation units, and (ii) sensing and adjustment means, provided in-line between each separation unit, for continuously monitoring and adjusting at least one environmental property parameter of fluid flowing from one separation unit to a subsequent separation unit in the line of separation units. Uses of the separation system and a method for purification of a liquid containing a desired species, using separation units and in-line adjustment of a fluid flow or flows, are also disclosed.
A process for a combined dual step separation of a mixture of two or more groups of molecular substances where the groups differ in their ability to be transported into and bound by two capture media, such that members of one group are largely excluded from the first media allowing them to flow through' to the second media is disclosed The capture media may both be based on similar base matnces and ligands but differ in other properties Examples of mixtures for processing in this manner include native and polysaccharide modified proteins, or native and synthetic polymer modified proteins The groups of molecules may themselves be heterogenous in regard to properties other than the above interactions This includes a group of monopolymer grafted proteins of protein to polymer molar ratio 1, whose members are heterogenous in regard to the position of polymer coupling to the protein
The present invention relates to a method for resuspending sedimented resins in a microtiter plate, comprising placing the microtiter plate containing pre-filled, sedimented resins on one of its sides; and shaking the microtiter plate to resuspend the sedimented resin pellet. Preferably, the microtiter plate is placed, standing on its side, on a shaker for resuspension. Most preferably, the microtiter plate is placed, standing on its side, on a plate holder block, and the plate holder block is placed on a shaker for resuspension. Optionally, the microtiter plate is secured on the shaker or the plate holder block, before the shaking step. Also provided is a plate holder block useful for the claimed method, as well as use of the plate holder block.
The invention provides a method for distinguishing biological materials. The method provides: providing at least one segmented image of at least two cells; applying a distance transform to the at least one segmented image of the confluent cells; applying a region growing technique to the distance transform of the at least one segmented image to form a region grown image, wherein a plurality of regions are formed in the at least one segmented image; assigning at least one label to at least one of the plurality of regions of the at least one segmented image of the confluent cells; applying a merging technique to at least two of the plurality of regions if it is determined that at least two of the plurality of regions are neighboring regions; determining whether to assign a same label to the neighboring regions or retain existing labels; and merging the neighboring regions of the region grown image if labels are changed to form at least one image of at least one cell.
A system for providing multiple images in an imaging unit is disclosed. A light source emits a beam of light to a sample. The sample receives the beam of light, wherein the sample emits a fluorescent beam of light in response to receiving the beam of light, where the fluorescent beam of light is split into a first wavelength beam and a second wavelength beam by a dichroic mirror. The dichroic mirror receives the first wavelength beam then transmits the first wavelength beam to at least one detector. The dichroic mirror receives the second wavelength beam that is transmitted through a first mirror, a second mirror and a third mirror to the at least one detector. The at least one detector simultaneously records and displays a first image from the first wavelength beam and a second image from the second wavelength beam.
Automated isothermal titration micro calorimetry (ITC) system comprising a micro calorimeter with a sample cell and a reference cell, the sample cell is accessible via a sample cell stem and the reference cell is accessible via a reference cell stem. The system further comprises an automatic pipette assembly comprising a syringe with a titration needle arranged to be inserted into the sample cell for supplying titrant, the pipette assembly comprises an activator for driving a plunger in the syringe, a pipette translation unit supporting the pipette assembly and being arranged to place pipette in position for titration, washing and filling operations, a wash station for the titrant needle, and a cell preparation unit arranged to perform operations for replacing the sample liquid in the sample cell when the pipette is placed in another position than the position for titration.
G01N 25/20 - Investigating or analysing materials by the use of thermal means by investigating the development of heat, i.e. calorimetry, e.g. by measuring specific heat, by measuring thermal conductivity
71.
A SYSTEM AND METHOD FOR ADJUSTING A BEAM EXPANDER IN AN IMAGING SYSTEM
A line confocal microscope system, comprising an illumination system with a source of collimated light and a line forming optics arranged to provide a line shaped illumination area to be scanned over a sample, an image receiving system, and two or more objective lenses that are interchangeable in the optical path to provide different magnification, wherein the objective lenses have different aperture diameters, and the illumination system comprises a beam shape transformer arranged in between the source of collimated light and the line forming optics to selectively transform the cross-sectional shape of the collimated beam of light transmitted to the line forming optics to a predetermined shape in response to the back aperture diameter of the objective lens that is arranged in the optical path.
G02B 26/08 - Optical devices or arrangements for the control of light using movable or deformable optical elements for controlling the direction of light
This invention relates to a simple and rapid method for the extraction and purification of small RNA from a sample solution. Accordingly, a sample is first mixed with an organic solvent to form a mixture containing the solvent. The mixture is applied to a first mineral support for large RNA to bind. The filtrate is collected which contain unbound small RNA, and is mixed with a second organic solvent to form a second mixture containing the second solvent. This second mixture is applied to a second mineral support for small RNA to bind. After a wash step, the small RNA is eluted. Also provided is a method for the isolation of large RNA, by eluting the large RNA from the first mineral support. In addition, total protein is present in the filtrate and can be isolated by a conventional method.
C12Q 1/68 - Measuring or testing processes involving enzymes, nucleic acids or microorganismsCompositions thereforProcesses of preparing such compositions involving nucleic acids
C07H 21/02 - Compounds containing two or more mononucleotide units having separate phosphate or polyphosphate groups linked by saccharide radicals of nucleoside groups, e.g. nucleic acids with ribosyl as saccharide radical
Methods and kits for generating circular nucleic acids in a cell-free system, and uses for the generated circular nucleic acids are provided. The methods comprise in vitro amplification of a nucleic acid template comprising a recombination site to produce tandem repeat nucleic acid sequence, and employ a recombination protein to generate the circular nucleic acids from the tandem repeat nucleic acid sequence.
Provided is a novel two step chromatographic purification process (load and elute) for the isolation of genomic DNA. In this method the sample is loaded on the column and the genomic DNA product is eluted directly without any intermediate wash steps. This is accomplished by utilizing a restricted access resin (i.e., lid beads), which is easy to prepare and comprised of two layers with different properties with non-functional surfaces on the outer layer. The inner layer is modified with functional groups that act as ion-exchangers. Small molecules such as RNA and proteins can enter the inner part of the resin and larger genomic DNA molecules will pass through the resin. RNA and proteins are captured in the inner layer of the restricted access resin while genomic DNA is readily eluted in the flow-through.
C12P 19/34 - Polynucleotides, e.g. nucleic acids, oligoribonucleotides
C07H 21/04 - Compounds containing two or more mononucleotide units having separate phosphate or polyphosphate groups linked by saccharide radicals of nucleoside groups, e.g. nucleic acids with deoxyribosyl as saccharide radical
75.
METHOD FOR SEPARATION OF DOUBLE-STRANDED AND SINGLE-STRANDED NUCLEIC ACIDS FROM THE SAME SAMPLE
The invention provides systems, methods and kits for the separation and/or purification of double-stranded and single-stranded nucleic acids from the same sample. The method includes first mixing a sample containing both double-stranded nucleic acid and single-stranded nucleic acid with a solution including a chaotropic salt and a non-ionic detergent to generate a mixture; then applying the mixture to a first mineral support for double-stranded nucleic acid to bind; and collecting the flow-through which contains unbound single-stranded nucleic acid. The method further includes diluting the non-ionic detergent of the flow-through, and applying the diluted flow-through to a second mineral support for the single-stranded nucleic acid to bind. Alternatively the flow-through can be mixed with a lower aliphatic alcohol prior to loading of the second column. The double-stranded and the single-stranded nucleic acids can be eluted from the mineral supports respectively.
This invention, which provides a method for detecting a corruption in an image acquired from a biological sample, includes: providing at least one image of at least one cell; generating the image of the at least one cell over a period of time; determining if the at least one image of the at least one cell is corrupted; applying a wavelet transform, Fourier transform, or other frequency decomposing transform to the at least one image to decompose the at least one image into a plurality of sub-images, wherein the plurality of sub-images have a plurality of low frequency channels, a plurality of middle frequency channels and a plurality of high frequency channels; calculating a ratio based on an energy level of the plurality of low frequency channels and the plurality of middle frequency channels; and removing the at least one image of at least one cell if the at least one image is corrupted.
A method is disclosed in which circular DNA molecules are amplified preferentially in a mixture of circular DNA molecules and linear DNA molecules by the inclusion of single strand DNA binding protein.
The invention provides systems, methods and kits for the separation and/or puπfication of double-stranded and single-stranded nucleic acids. The method includes first mixing a sample containing the double-stranded nucleic acid and the single-stranded nucleic acid with a pH-neutral, buffered solution consisting essentially of a chaotropic salt and a pH buffer to generate a mixture; applying the mixture to a first mineral support for the double-stranded nucleic acid to bind; and collecting the flow-through which contains unbound single-stranded nucleic acid. The method further includes adjusting the pH of the flow-through to an acidic pH, or the flow-through can be mixed with a lower aliphatic alcohol, prior to loading of a second support. The double-stranded and the single-stranded nucleic acids bound can be eluted from the mineral supports respectively.
The invention provides a method for the separation and purification of two or three cellular components selected from genomic DNA, RNA and proteins from a single biological sample. The method comprises generating an aqueous solution containing the cellular components by lysing cells with a lysis solution; contacting the aqueous solution with an ion exchanger for genomic DNA and RNA to bind to the ion exchanger; collecting the flow-through which contains unbound proteins; eluting RNA from the ion exchanger; and eluting DNA from the ion exchanger. For the purification of any two of the cellular components, one of the components is not collected. The invention also provides reagent kits for carrying out the methods.
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
The present invention provides methods, formulation and kits for the synthesis of long nucleic acid fragments. An improved PCR method is provided for amplifying long DNA fragments. In particular, a single thermostable DNA polymerase is used for the rapid amplification of over 10 kb long DNA fragments. Also provided is a method for extending long complementary DNA strands using this single enzyme formulation.
The present invention relates to a method for sterilization of a chemically activated solid support material comprising exposing the solid support material to pressurized steam at a temperature of between about 121oC and about 135oC. Also provided are sterile, activated solid support material produced according to the present method, including chromatographic separation medium made thereof.
B01J 20/00 - Solid sorbent compositions or filter aid compositionsSorbents for chromatographyProcesses for preparing, regenerating or reactivating thereof
82.
METHOD FOR ISOLATION OF GENOMIC DNA, RNA AND PROTEINS FROM A SINGLE SAMPLE
The invention provides systems, methods and kits for the separation and/or purification of at least two cellular components selected from genomic DNA, RNA and proteins. The method includes first lysing a biological sample to generate an aqueous solution containing the cellular components; then applying the aqueous solution to a first mineral support under conditions for genomic DNA to bind; and collecting the flowthrough which contains unbound total RNA and proteins. The method further includes applying the flowthrough to a second mineral support under conditions for RNA to bind, and collecting the flowthrough which contains proteins. The genomic DNA and total RNA bound can be eluted while the protein in the flowthrough can be further purified. Further the total RNA isolated could be used to isolate small RNA such as microRNA.
An automatic pipette assembly for an isothermal titration micro calorimetry system, comprising a pipette housing, a syringe with a titration needle arranged to be inserted into a sample cell for supplying titrant, and a linear activator for driving a plunger in the syringe, the titration needle is rotatable with respect to the housing and is provided with a stirring paddle arranged to stir fluid in the sample cell, wherein the automatic pipette assembly comprises a stirring motor for driving the rotation of the titration needle. There is also provided an isothermal titration micro calorimetry system.
G01N 25/20 - Investigating or analysing materials by the use of thermal means by investigating the development of heat, i.e. calorimetry, e.g. by measuring specific heat, by measuring thermal conductivity
The present invention relates to a method for sterilization of a chromatographic separation medium wherein the chromatographic separation medium comprises proteinaceous ligands bound to a solid matrix. The method comprises exposing the separation medium to pressurized steam at a temperature of between 121°C and 135°C.
B01J 20/00 - Solid sorbent compositions or filter aid compositionsSorbents for chromatographyProcesses for preparing, regenerating or reactivating thereof
This invention provides a system and method that allows a user to adjust the amount of laser light that is coupled into a fiber when the laser beam is focused on to the fiber tip using an optical lens. The user is able to determine the initial amount of laser light that is emanating from the output end of the fiber or fiber bundle, then the user is able to adjust the fiber coupler system to maximize the light output. This fiber coupler system provides the user with a simple and automated method for adjusting the fiber coupler system so it can maximize the light entering the fiber tip.
The invention provides an modified method for the separation of nucleic acids from cells, comprising: generating an aqueous solution containing the nucleic acid by lysing the cells with a lysis solution including SDS and salt; and separating the nucleic acids of interest from other cellular components. The improvement includes adding a non-ionic detergent in the lysis solution such that SDS is not precipitated and no heating of the solution is required prior to cellular lysis. The preferred non-ionic detergents are the polysorbate family of compound, including Tween 20. Also disclosed are composition and kit for performing the modified method.
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
87.
SYSTEM AND METHOD FOR ASSEMBLING A LARGE SCALE CHROMATOGRAPY STRUCTURE
A container system is disclosed, where the container system includes a housing. A chromatography cartridge is disposed in the housing. A structural support in the housing is configured to retain the chromatography cartridge within the housing. The housing is configured to withstand a certain amount of pressure generated inside the chromatography cartridge. The chromatography cartridge is disposed in the housing either in horizontal or in vertical position.
The present invention relates to methods and compositions for providing purified thermostable enzymes, particularly thermostable DNA polymerases, that are free of exogenous detergents The present invention also provides methods for providing such purified thermostable DNA polymerases to assays in an active form by adding one or more detergents The present invention further provides compositions and kits comprising purified thermostable DNA polymerases for use in a variety of applications, including amplification and sequencing of nucleic acids.
The invention relates to a modified spin column for the isolation and purification of plasmid DNA. A pre-filtration disc is included in a traditional spin column. During plasmid DNA isolation, the lysate can be loaded directly to the modified spin column, eliminates the need to first remove the flocculants containing cellular debris. This results in a much shortened process. Variation of the invention includes a depth filter in between the pre-filtration disc and the main separation matrix. Also provided are kits for isolation of plasmid DNA including the modified spin columns.
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
90.
IMPROVED MINIPREP SYSTEM FOR SIMPLE AND RAPID PLASMID DNA EXTRACTION
The invention relates to a modified microspin system for the isolation and purification of plasmid DNA. A disposable pre-filter column is used in combination with the traditional microspin column for increase speed and quality of plasmid DNA preparation. The disposable pre-filter column includes a pre-filter and a depth filter for optimal result. During plasmid DNA isolation, the lysate can be loaded directly to the assembly including the disposable pre-filter column and the microspin column. A quick spin causes the plasmid DNA to bind to the microspin column while the flocculents remain on top of the disposable pre-filter column, eliminates the need to first remove the flocculants containing cellular debris. This results in a much shortened process. Also provided are kits for isolation of plasmid DNA including the pre-filter column and the microspin columns.
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
C12Q 1/68 - Measuring or testing processes involving enzymes, nucleic acids or microorganismsCompositions thereforProcesses of preparing such compositions involving nucleic acids
91.
SYSTEM AND METHOD FOR THE AUTOMATED ANALYSIS OF CELLULAR ASSAYS AND TISSUES
A method for providing an image of a biological sample is disclosed. The method includes: obtaining an image of at least one biological sample; positioning the image of the at least one biological sample; assessing the image of the at least one biological sample; automatically segmenting the image of the at least one biological sample; while simultaneously determining a region of interest of the at least one biological sample; responsive to obtaining the image of the at least one biological sample and a control parameter of the at least one biological sample; and receiving the region of interest and providing an indication of a location of the region of interest.
A system (100) for measuring parameters in a container (101) is disclosed. The container (101) has a solution (101a). A protective layer (105) is deposited over at least one sensor (103) and at least one wall (101b) of the container, where the protective layer (105) is attached to the wall (101b) of the container to form a seal between the container and the at least one sensor (103). The at least one sensor is.configured to have an operable electromagnetic field based on a thickness of the container and the protective layer. The at least one sensor in conjunction with a.tag (102) is in proximity to an impedance analyzer (108) and a reader (106) that constitute a measurement device (111). The at least one sensor (103) is configured to determine at least one parameter of the solution. The tag (102) is configured to provide a digital ID associated with the' at least one sensor, where the container (101) is in proximity to the reader (106) and an impedance analyzer (108). The impedance analyzer is configured to receive a given range of frequencies from the at least one sensor (103) based on the measured complex impedance over the given range of frequencies.
The present invention provides a biological sample preparation system including ambient temperature stable reagent mixture and a separation filter or membrane. In particular, the system includes a dried reagent in a glassy, porous state, on top of a separation column, whereby sample preparation is streamlined and simplified. Also provided are methods of making and using the system. A kit for preparing a biological sample is also provided.
Improved processes for the amplification of target DNA sequences in the form of single or double stranded circular DNA molecules, especially those present in colony and plaque extracts, using multiple specific and/or random sequence oligonucleotide primers are disclosed. The product of this amplification is used for analysis by restriction enzyme digestion or DNA sequencing and other analyses that involve hybridization. Kits containing components for use in the method are also described. Also described are further uses of this amplified DNA in sequencing, genotyping and haplotyping, and other molecular biology applications.
This invention provides for the fully automated, hands free, packing of chromatography columns by means of delivering a pre-calculated volume of slurry and using two different packing modalities to stop the packing when either 1) this volume has been delivered in the column, or 2) when the adapter is moved to reach a bed height corresponding to the pre-calculated volume. Thus, a chromatography column can be packed in a fully automated fashion and such a column is 1)stable and 2) has the desired performance characteristic.
A spherical aberration adjustment system is disclosed, which includes a plurality of objective lenses, where at least one of the plurality of objective lenses has a spherical aberration collar. The plurality of objective lenses are mounted onto an objective holder, where the objective holder is configured to place the at least one of the plurality of objective lenses in an imaging position. A driving mechanism is coupled by a mechanical link to the at least one of the plurality of objective lenses, where the mechanical link is configured to transmit motion from the driving mechanism to the spherical aberration collar. A control system is configured to manipulate the driving mechanism to move the spherical aberration collar of the at least one of the plurality of objective lenses in the imaging position to a specific spherical aberration adjustment setting.
G02B 7/04 - Mountings, adjusting means, or light-tight connections, for optical elements for lenses with mechanism for focusing or varying magnification
97.
SYSTEM AND METHOD FOR TRACKING THE MOVEMENT OF BIOLOGICAL MATERIALS
This invention provides an automated system and method that allows a user to track the movement of an object, such as at least one cell amongst a plurality of cells as it moves from one point to another over time in order for the user to determine how the at least one cell functions. The user is able to track the movement of the at least one cell and determine if the at least one cell structure has changed, such as the at least one cell experiencing cell division or if two or more cells merge together. This user is able to optimally track the at least one cell to find an approximate location of at least one the cell as it moves in time and distance. Thus, this invention provides the user with a means to track cell movement to study the cell function.
G06F 19/00 - Digital computing or data processing equipment or methods, specially adapted for specific applications (specially adapted for specific functions G06F 17/00;data processing systems or methods specially adapted for administrative, commercial, financial, managerial, supervisory or forecasting purposes G06Q;healthcare informatics G16H)
This invention provides a system and method that allows for time-resolved fluorescent imaging of fluorescent samples. The user is able to receive temporally filtered pictures of the sample with a reduced amount of the scattered excitation light and the short lived background fluorescence. The system allows for adjustment of fluorescent gating time and delay time.
The invention provides an improved method for the purification of nucleic acid molecules, which method comprises generating a cellular lysate containing the nucleic acid; contacting the lysate with an anion exchanger bound to a solid support matrix under conditions such that the anion exchanger binds the nucleic acid; followed by eluting the nucleic acid from the anion exchanger with an aqueous mobile phase comprising an elution solution; and desalting the eluted nucleic acid such that it is suitable for downstream applications. The improvement of the method includes adding in the elution solution a composition such that the pH of the aqueous mobile phase is between about pH 9 and about pH 13, wherein the presence of the composition in the elution solution provides an increase in nucleic acid recovery, as compared with the recovery in the absence of the composition.
Disclosed is a process for separating and/or purifying a nucleic acid by elution of the nucleic acid from anion exchange resins under conditions of high salt concentration and the presence in the eluant of an additive comprising guanidine, or a guanidine-like derivative. The process allows high recovery of nucleic acids from anion exchange resins without impairing the nucleic acid stability as compared with conventional ion exchange chromatographic procedures.
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