WO2005080967A1 - Method and device for the characterization of interactions between different species - Google Patents
Method and device for the characterization of interactions between different species Download PDFInfo
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- WO2005080967A1 WO2005080967A1 PCT/SE2005/000203 SE2005000203W WO2005080967A1 WO 2005080967 A1 WO2005080967 A1 WO 2005080967A1 SE 2005000203 W SE2005000203 W SE 2005000203W WO 2005080967 A1 WO2005080967 A1 WO 2005080967A1
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- Prior art keywords
- liquid
- species
- support
- solid support
- ligand
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Classifications
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- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
- B01L3/00—Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
- B01L3/50—Containers for the purpose of retaining a material to be analysed, e.g. test tubes
- B01L3/508—Containers for the purpose of retaining a material to be analysed, e.g. test tubes rigid containers not provided for above
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
- G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
- G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
- G01N33/53—Immunoassay; Biospecific binding assay; Materials therefor
- G01N33/543—Immunoassay; Biospecific binding assay; Materials therefor with an insoluble carrier for immobilising immunochemicals
- G01N33/54366—Apparatus specially adapted for solid-phase testing
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
- B01L2300/00—Additional constructional details
- B01L2300/06—Auxiliary integrated devices, integrated components
- B01L2300/0627—Sensor or part of a sensor is integrated
- B01L2300/0636—Integrated biosensor, microarrays
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
- B01L2400/00—Moving or stopping fluids
- B01L2400/04—Moving fluids with specific forces or mechanical means
- B01L2400/0403—Moving fluids with specific forces or mechanical means specific forces
- B01L2400/0409—Moving fluids with specific forces or mechanical means specific forces centrifugal forces
Definitions
- the present invention relates to the field of characterization of how different species interact with each other. More in particular, it relates to a method where one or more of the species are attached to a solid support and the other species are put in a liquid that is contacting the solid support. Even more in particular, it relates to the interaction of species of biological or chemical origin, e.g. cells, proteins, DNA, RNA, tissue, synthesized chemical compounds and the like.
- the immune system is a first example, where antibodies in the bloodstream interact with pathogens and thereby guide natural killer cells to the pathogen.
- Therapeutic drugs is a second example, where a drug may interact with an enzyme in a way that inhibit the enzyme activity.
- a third example is detection of diseases in humans or animal, by contacting a sample from the human or animal with a liquid containing a species that interacts specifically with the pathogen causing the disease. If the species remains on the sample after a wash step, the sample is carrying the pathogen causing the disease. Exactly the same method can be used to detect contamination in food stuff. This means that methods and devices for characterization of interactions between species are important not only for research and diagnostics in biology and medicine, but also in quality control and characterization assays in a variety of fields.
- the bifunctional species should (a) have a property that is easily detectable (e.g.. be radioactive or have a fluorescent moiety attached to it) and (b) interact with the species that is attached to the solid support.
- the liquid is brought into contact with the solid support, sometimes followed by a wash of the solid support in a liquid without the bifunctional species. If the bifunctional species interacts stably with the species on the solid support it will accumulate on the solid support and remain there after a wash. Presence of the bifunctional species can then be detected.
- Another, more complicated method that has been widely used for the characterization of interactions is enzyme linked immunosorbent assay (ELISA) .
- the present invention aims at facilitating the characterization of how species interact with each other.
- the method is particularly suitable when one of the species is large (in a molecular context), e.g. if one of the species is cells or bacteria.
- Pierce Biotechnology Inc (Rockford, IL, United States of America) manufactures and sells a microplate where the bottom of each well has up to 16 defined areas where antibodies that recognize specific proteins are attached (SearchlightTM).
- SearchlightTM antibodies that recognize specific proteins are attached
- the detection of the different proteins is mediated by secondary antibodies, one for each specific protein, labeled with a moiety that emits light.
- a camera is then used to quantify the light intensity, which is related to the specific protein concentration, on each defined area. This method is presently limited to proteins and does not explicitly use one defined area for reference purposes.
- Biacore AB Uppsala, Sweden manufactures an optical biosensor (Biacore®3000) that has a solid support with 4 defined areas where different species can be attached. Liquid samples are injected onto the solid support. If a species present in the liquid is binding to the species attached to the solid support, the refractive index close to the solid support will change. The optical detection system monitors refractive index close to the solid support in real time.
- the biodisc is an essentially flat plastic disc which includes radial oriented channels with inlet and outlet ports. In each channel there is a plurality of target zones onto which different antibodies are immobilized. Some target zones have antibodies recognizing antigens on cells that are specific for a unique blood type. Other target zones serve as negative or positive controls.
- a cell suspension e.g. a blood sample, is injected into a channel. Certain cells in the suspension may then bind to the target zone carrying antibodies specific for the blood type of the patient.
- the disc is rotated to move all unbound cells away from the target zones.
- the blood type of the patient can be determined by optically detecting which target zones cells have bound to. This means that the biodisc measurement does not necessarily include a wash step, instead unbound cells are completely removed from the detection area by accelerated sedimentation caused by rotating the disc at a high speed.
- the object of the present invention is to facilitate the characterization of how different species interact with each other.
- the invention provides a device for the characterization of interaction between species. This device is defined in claim 1.
- the invention provides a method for the characterization of how different species interact with each other.
- the method according to the invention is defined in claim 6.
- the invention in a preferred embodiment has four characteristic features.
- a solid support with at least two defined areas, namely one for a target and at least one for reference purposes. However, several different targets can be provided in separate defined areas.
- a liquid containing a dissolved ligand is in contact with the solid support to enable an interaction between target and ligand.
- a detector is arranged so as to be able to detect and quantify the presence of the ligand near the defined areas.
- stirring of the liquid in contact with the solid support is provided for.
- An essential feature is provision of means for at least temporarily reducing the amount of liquid at a defined area during detection.
- Figure 1 shows a schematic of one possible instrument design
- Figure 2 a shows data acquired with a very low concentration of the ligand
- Figure 2 b shows data acquired with a high concentration of the ligand
- Figure 3a and 3b illustrates how the acquired data is processed prior to evaluation
- Figure 4 shows how different concentrations of a ligand give rise to different signals
- Figure 5 shows how different concentrations of a ligand give rise to different signals obtained with and without a wash step, respectively.
- targets and ligands include, but are not limited to, tissue samples, cells, bacteria, viruses, solid particles, macromolecules (e.g. proteins, DNA, RNA) and other chemical compounds.
- Preferred ligands include macromolecules (e.g. proteins, DNA, RNA), other chemical compounds and any species that can be dissolved in a liquid.
- the present invention aims at improving the accuracy and precision of the characterization of interactions between different species. Another aim is to reduce the labor time required for performing a characterization.
- a device for detecting interactions between species attached to a support (targets) and species in a liquid (ligands), when said support and said liquid are brought into contact; comprises: a solid support (11) on which a first species can be attached in one or more non-overlapping defined areas thereon; a detector (12) capable of detecting an interaction between said species attached to the solid support, and said species contained in said liquid.
- the device is charaterized by a mechanism (16) adapted for temporarily reducing, in a defined area of said support, the amount of liquid with which said support is brought into contact in the course of a detection; and at least one of the defined areas do not have a species of interest attached, so as to form a reference area for the detection.
- the second species can preferably be present in the liquid as a dissolved molecule or a dissolved complex of molecules with a total molecular weight less than 1000000 g/mole.
- the solid support is an essentially flat dish capable of holding a liquid confined within its boundaries, such as a Petri dish, although any other kind of receptacle or vessel capable of confining liquid is possible.
- the invention provides in one embodiment an aspirating device for aspirating liquid from said support before measurement, and for returning liquid to the support after measurement.
- the detector 12 is a scintillation detector, although many other types of detectors are possible, see below.
- an electronic counter device 13 for counting the impulses from the detector 12, and a control unit for adjusting and reporting the angular position of the support 11, and a computer 15 for synchronizing scintillation counter output from the counter 13 and the angular position of the cell dish support from the control unit 14.
- the method according to the invention comprises attaching a first species on a defined portion of a solid support. Then said first species (target) is exposed to a liquid containing a second species (ligand), so as to cover the defined portion of the solid support. A measurement is performed, capable of detecting an interaction between said first and said second species. According to the invention the amount of liquid covering the defined portion of the support is temporarily reduced prior to performing said measurement. A reference measurement is performed on a different portion of the solid support where no interaction takes place, said portion defining a reference area.
- the temporary reduction of liquid comprises a reduction of the amount of liquid near at least one of said defined areas without changing the total amount of liquid in contact with said solid support.
- a difference between target and reference measurements is calculated.
- the sequence of steps of exposing, measuring and reducing the amount of liquid is preferably repeated, and the concentration of said ligand is increased by a finite amount before said sequence of steps is repeated.
- the interactions on all defined areas are detected within 1 minute, and the detection of all interactions are preferably repeated without interruption during at least 15 minutes in order determine the progress of the interaction over time.
- the reduction of the amount of liquid is achieved by orienting the support at an angle that deviates from the horizontal to provide an elevated part and a lower part of said support, such that the elevated part will be covered by less liquid than the lower part, and wherein the support is rotated at a predetermined speed of rotation.
- the first species is selected from tissues, cells, bacteria, virus particles, and the second species present in the liquid is a dissolved molecule or a dissolved complex of molecules with a total molecular weight less than 1000000 g/mole.
- a device comprising four main characteristics is used for the characterization of interactions between ligands and targets. Namely, on one single solid support two or more areas are defined, where at least one area is reserved for attaching a target (also referred to as an active area) and at least one area is reserved for reference purposes. A reference area either has nothing attached to it or has an irrelevant target attached to it. Furthermore, liquid containing a ligand is in contact with the solid support. There is also a detection system able to detect presence and quantity of the ligand on each area. There is a mechanism for stirring the liquid present on the solid support. Finally, there is a mechanism that ensures that the amount of liquid present close to a defined area is temporarily reduced during detection.
- Commonly used methods for characterization of interactions between targets and ligands often include a wash step.
- the purpose is to remove all ligand that has not bound to the target, since presence of unbound ligand may be detected.
- a wash step is not necessary due to the use of a reference area and due to the temporary reduction of liquid during detection. Since the presence of ligand is quantified at all areas in short time and since the liquid containing ligand is temporarily reduced, the reference area will mimic the active area in terms of radiation associated with unbound ligand in the remaining liquid close to the area and background radiation.
- a wash step can increase the sensitivity in cases where a very high concentration of ligand is present in the liquid.
- liquid containing ligand can be reused throughout a characterization. This is of particular interest when the ligand is expensive.
- a liquid with low concentration of ligand is put into contact with the solid support. After characterization of this first concentration a small aliquot of highly concentrated ligand is added. The total concentration of ligand then increases to a second level, and the binding is characterized. This process is repeated until the desired concentrations have been characterized.
- the solid support is typically a container. In this container two or more defined areas are present. Liquid put in the container contacts all defined areas. At least one defined area is always reserved for reference purposes. This makes it possible to characterize the interaction of one ligand with several targets simultaneously. Another possibility is to use a detection system that can distinguish different ligands, e.g. by attaching different fluorescence dyes on the different ligands and detecting the light intensity at the different characteristic emission wavelengths corresponding to the defined dyes. With this setup, several ligands can be put in one liquid and binding of all ligands to one or more targets can be characterized simultaneously.
- the attachment of target on the defined areas can be performed in a variety of ways.
- Cells could be grown directly on a defined area.
- the defined areas could be coated with a protein known to enhance attachment of cells.
- the defined areas could be coated with a protein known to bind a specific molecule which is used for attachment of the target.
- One such protein is streptavidin which binds biotin strongly.
- a biotinylated target e.g. biotinylated DNA
- the surface of the defined areas could be chemically modified to make possible covalent attachment of a target. Passive adsorption of target directly onto the defined area is also possible.
- the surface of the defined areas is not necessarily solid and flat. Porous surfaces or surfaces with biopolymers attached (e.g. polyethylene glycol or dextran) could be advantageous due to increased target density making a higher signal possible.
- the defined areas on the solid support do not need to be explicitly marked.
- a drop of cells can be put on the solid support, leaving the majority of the solid support clean for reference purposes.
- more liquid (without cells) can be carefully added to the solid support to prevent the cells from drying.
- Detectors that are in physical contact with the solid support and detectors that are not in physical contact with the solid support.
- Detector principles that do require physical contact with the solid support include (but are not limited to) electrochemical detection of ligand, refractometric detection of ligand.
- Detector principles that do not require physical contact with the solid support include (but are not limited to) detection of radioactivity, detection of emitted light (e.g. using fluorescence or chemoluminence), spectrophotometric detection, just to mention a few.
- the detection system used in this method is time resolved.
- detection of a defined area is repeated at least every tenth minute, preferably every 20-60 seconds, even more preferably every 0.1-20 seconds.
- the time-resolved measurement makes it possible to monitor the rate of ligand binding to the target, also known as the kinetics of the interaction.
- a mechanism that temporarily decreases the amount of liquid in the vicinity of the defined area during detection is beneficial but not necessary.
- the method relies on differential measurements (i.e. signal from active area minus signal from reference area) and as such it should not, in theory, be affected by excess of liquid present in the vicinity of the defined area during detection. In practice, performance may increase when such excess liquid is temporarily removed.
- the problem is that for some detection principles, e.g. detection of radioactivity, the amount of ligand present in a volume close to the detector will be detected. This volume includes the defined area and the liquid present near the defined area.
- the amount of unbound ligand present in the liquid will often be much larger than the amount of ligand bound to the target, which means that the detector will register almost the same amount of radioactivity during detection of an active area and a reference area.
- the resolution for such differential measurements can sometimes be low.
- This problem can be overcome by temporarily reducing the amount of liquid covering the solid support during detection.
- the liquid remaining on the defined areas might then contain enough ligand to be detected, but the magnitude of the liquid-associated signal will be comparable to the magnitude of the signal associated with the defined area.
- the currently preferred method avoid detrimental impact of signal from unbound ligand present in the liquid is to completely remove the liquid.
- the most common method used to remove the liquid containing ligand is to wash the solid support with a suitable liquid devoid of ligand.
- KD is the equilibrium dissociation constant for the target-ligand interaction
- [T] is the concentration of unbound target
- [L] is the concentration of unbound ligand
- [TL] is the concentration of target- ligand complexes.
- One possible method to reduce the amount of liquid near a defined area on the solid support is to use a circular solid support (e.g. a cell dish) and put defined areas along the perimeter of the solid support. If such a solid support is placed on a rotating disk that is mounted with a slight slope it becomes possible to position a defined area at the highest position during detection. Liquid present on the solid support will accumulate in the lower end of the solid support and will not severely impact the quantification of ligand on the defined area.
- Another possible method for temporarily moving liquid on the solid support is to tilt the solid support during detection. If the defined areas are put in one end of a solid support and this end is elevated during detection, liquid present on the solid support will accumulate in the other end and make a more reliable detection possible.
- a third possible method is to use a pump that aspirates the liquid on the solid support during detection, and dispenses the liquid back onto the solid support afterwards. It is notable that all these methods also provide a stirring of the liquid present on the solid support.
- the amount of liquid that remains on the defined area during detection should be less than 10%, preferably less that 5% and even more preferable less than 1% of the amount of liquid present in the vicinity of the defined area when the solid support is positioned horizontally in rest. This could be measured using a solid support without any target attached to the defined areas and compare the signal from a defined area in horizontal position with the signal from the same defined area in position for detection with the liquid temporarily removed.
- a sufficient reduction of liquid with ligand on the defined area can be defined in terms of background signal contribution.
- liquid still present on the defined area during detection give a background signal that is at most ten times, and preferably at most two times, the expected signal originating from ligand bound to target.
- the acceptable amount of remaining liquid cannot easily be expressed in terms of per cent removal, because the value depend many parameters (e.g. the concentration of the ligand, the affinity of the interaction and the initial volume of the liquid in the solid support).
- an interaction would be measurable when 0.1-1% of the liquid is still present on the defined area during detection if the affinity is approximately lxlO- 8 M, the ligand concentration in the range of 1x10-° M to 5xl0- 9 M, the solid support is a Petri dish with a diameter of approximately 10 cm and the liquid volume is approximately 2 ml.
- a stirring device is required. This could be a vibrating rod or a rotating propeller that is put in the liquid. Alternatively, the solid support could be moved repeatedly to induce movements in the liquid. Possible motions include gentle shaking and excentric rotation.
- FIG. 1 The physical structure of one embodiment of a device according to the invention is illustrated in figure 1.
- a radioactively labeled ligand is used, whereby the target will become radioactive when ligand binds thereto.
- the device comprises two key components, (i) a cell dish support that can be rotated slowly 11. (ii) a time-resolved scintillation counter 12 mounted such that it will detect interactions present only on a peripheral part of the cell dish.
- a stepper motor 16 is connected to the cell dish support 11.
- the motor is controlled by an electronic device 14 that both can adjust the angular position and report the angular position of the cell dish support.
- the scintillation detector 12 is connected to an electronic device 13 that counts the number of impulses from the detector 12.
- the cell dish support is inclined and the scintillation counter is located at the highest point of the cell dish support.
- the scintillation counter is read with a high frequency to allow multiple activity measurements during one round.
- a computer 15 synchronizes scintillation counter output from 13 and the angular position of the cell dish support from 14 and generates an activity versus angular position curve.
- the target here human cancer cells
- the target are grown only on a limited sector of the cell dish, as indicated in white in figure 1.
- a liquid containing the ligand in this case a radioactively labeled protein, is added to the cell dish. It is known that the ligand binds to receptors present on the target cell surface. As the dish rotates, the activity of the dish bottom will be continuously monitored, sometimes an area with target cells, sometimes an area without target cells. If the ligand binds to the target cells, an increase of the radioactivity will be registered by the scintillation counter when the target cell sector of the cell dish passes the detector.
- the solid support i.e. the cell dish
- the detector is mounted in a peripheral part of the cell dish.
- the stirring is obtained by mounting the cell dish non- horizontally.
- the cell dish rotates, the liquid will start to rotate but with a different speed than the cell dish.
- the temporary removal of liquid is also obtained by mounting the cell dish non-horizontally.
- the detector is mounted near the highest point of the cell dish which is the point where there is the least amount of liquid.
- EGF is known to bind to the EGF receptor
- U343 cells are known to have high levels of EGF receptors on their surface.
- the radioactivity was measured at least 2 times per second giving approximately 20 measurements per round. Since EGF is known to bind to the cells, the measured radioactivity will be higher when the area of the cell- dish holding target cells passes by the detector compared to other times. This gives a continuous wave-like time series where the period is determined by the angular speed of the dish and the amplitude by the amount of EGF binding to the cells.
- the signal for each sample was determined as described above, by overlaying peak-to-peak fragments, averaging and extracting the wave amplitude. A signal versus concentration plot is found in figure 4. It clearly resembles the sigmoidal curve expected from a binding experiment. The first three samples were measured directly without a wash step (point 3 in the sequence of operation above), which explains the discontinuity between sample 3 and sample 4.
- A431 cells were grown on a limited area on a 8 cm cell dish. A431 cells also have high levels of EGF receptor on the surface.
- the sequence of operation in this experiment was:
- S is the measured signal for ligand concentration cone
- Smax is the binding capacity of the targets in the defined area
- KD is the affinity of the interaction.
Abstract
Description
Claims
Priority Applications (7)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
AU2005215573A AU2005215573B2 (en) | 2004-02-20 | 2005-02-16 | Method and device for the characterization of interactions between different species |
US10/588,011 US7867753B2 (en) | 2004-02-20 | 2005-02-16 | Method and device for the characterization of interactions between different species |
JP2006554051A JP4621693B2 (en) | 2004-02-20 | 2005-02-16 | Method and apparatus for characterizing interactions between different species |
BRPI0507855A BRPI0507855B1 (en) | 2004-02-20 | 2005-02-16 | method and device for characterizing interactions between different species |
CA002556686A CA2556686A1 (en) | 2004-02-20 | 2005-02-16 | Method and device for the characterization of interactions between different species |
EP05711063.7A EP1723411B1 (en) | 2004-02-20 | 2005-02-16 | Method and device for the characterization of interactions between different species |
CN2005800055713A CN1922483B (en) | 2004-02-20 | 2005-02-16 | Method and device for the characterization of interactions between different species |
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
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SE0400403-2 | 2004-02-20 | ||
SE0400403A SE0400403D0 (en) | 2004-02-20 | 2004-02-20 | Method and device for the characterization of interactions between different species |
Publications (2)
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WO2005080967A1 true WO2005080967A1 (en) | 2005-09-01 |
WO2005080967A8 WO2005080967A8 (en) | 2005-11-03 |
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Application Number | Title | Priority Date | Filing Date |
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PCT/SE2005/000203 WO2005080967A1 (en) | 2004-02-20 | 2005-02-16 | Method and device for the characterization of interactions between different species |
Country Status (9)
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US (1) | US7867753B2 (en) |
EP (1) | EP1723411B1 (en) |
JP (1) | JP4621693B2 (en) |
CN (1) | CN1922483B (en) |
AU (1) | AU2005215573B2 (en) |
BR (1) | BRPI0507855B1 (en) |
CA (1) | CA2556686A1 (en) |
SE (1) | SE0400403D0 (en) |
WO (1) | WO2005080967A1 (en) |
Cited By (6)
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WO2008088288A1 (en) * | 2007-01-18 | 2008-07-24 | Ridgeview Instruments Ab | Method for the quality control of molecules or targets |
WO2009029039A1 (en) * | 2007-08-28 | 2009-03-05 | Ridgeview Instruments Ab | Method for measurement of cell viability |
WO2010033069A1 (en) * | 2008-09-19 | 2010-03-25 | Ridgeview Instruments Ab | Method for the analysis of solid biological objects |
WO2016036301A1 (en) | 2014-09-01 | 2016-03-10 | Ridgeview Instruments Ab | Solid support for improved detection of interaction between species |
WO2017171606A1 (en) * | 2016-03-29 | 2017-10-05 | Ridgeview Instruments Ab | Method for the detection of molecules being in close proximity |
EP2856166B1 (en) * | 2012-06-01 | 2017-11-08 | Ridgeview Diagnostics AB | Method for the diagnosis of mammals |
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WO2002076475A2 (en) * | 2001-03-23 | 2002-10-03 | Bioparken As | Glycosaminoglycan anticoagulants derived from fish |
WO2016002729A1 (en) | 2014-06-30 | 2016-01-07 | パナソニックヘルスケアホールディングス株式会社 | Substrate for sample analysis, sample analysis device, sample analysis system, and program for sample analysis system |
US10309976B2 (en) | 2014-06-30 | 2019-06-04 | Phc Holdings Corporation | Substrate for sample analysis, sample analysis device, sample analysis system, and program for sample analysis system |
JP6588909B2 (en) * | 2014-06-30 | 2019-10-09 | Phcホールディングス株式会社 | Sample analysis substrate, sample analysis system, and method for removing liquid from liquid containing magnetic particles |
EP3163306A4 (en) | 2014-06-30 | 2018-01-24 | Panasonic Healthcare Holdings Co., Ltd. | Substrate for sample analysis, and sample analysis apparatus |
JP6660305B2 (en) | 2014-12-12 | 2020-03-11 | Phcホールディングス株式会社 | Sample analysis substrate, sample analyzer, sample analysis system, and program for sample analysis system |
CN107530486B (en) * | 2015-05-08 | 2020-12-11 | 生物磁溶液有限公司 | Apparatus and method for immunomagnetic cell separation |
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2004
- 2004-02-20 SE SE0400403A patent/SE0400403D0/en unknown
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2005
- 2005-02-16 US US10/588,011 patent/US7867753B2/en active Active
- 2005-02-16 CA CA002556686A patent/CA2556686A1/en not_active Abandoned
- 2005-02-16 AU AU2005215573A patent/AU2005215573B2/en not_active Ceased
- 2005-02-16 WO PCT/SE2005/000203 patent/WO2005080967A1/en active Application Filing
- 2005-02-16 BR BRPI0507855A patent/BRPI0507855B1/en not_active IP Right Cessation
- 2005-02-16 JP JP2006554051A patent/JP4621693B2/en not_active Expired - Fee Related
- 2005-02-16 EP EP05711063.7A patent/EP1723411B1/en active Active
- 2005-02-16 CN CN2005800055713A patent/CN1922483B/en not_active Expired - Fee Related
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Cited By (10)
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WO2008088288A1 (en) * | 2007-01-18 | 2008-07-24 | Ridgeview Instruments Ab | Method for the quality control of molecules or targets |
US8394646B2 (en) | 2007-01-18 | 2013-03-12 | Ridgeview Instruments Ab | Method for the quality control of molecules or targets |
WO2009029039A1 (en) * | 2007-08-28 | 2009-03-05 | Ridgeview Instruments Ab | Method for measurement of cell viability |
WO2010033069A1 (en) * | 2008-09-19 | 2010-03-25 | Ridgeview Instruments Ab | Method for the analysis of solid biological objects |
EP2331953A1 (en) * | 2008-09-19 | 2011-06-15 | Ridgeview Instruments AB | Method for the analysis of solid biological objects |
EP2331953A4 (en) * | 2008-09-19 | 2012-02-29 | Ridgeview Diagnostics Ab | Method for the analysis of solid biological objects |
US8709828B2 (en) | 2008-09-19 | 2014-04-29 | Ridgeview Diagnostics Ab | Method for the analysis of solid objects |
EP2856166B1 (en) * | 2012-06-01 | 2017-11-08 | Ridgeview Diagnostics AB | Method for the diagnosis of mammals |
WO2016036301A1 (en) | 2014-09-01 | 2016-03-10 | Ridgeview Instruments Ab | Solid support for improved detection of interaction between species |
WO2017171606A1 (en) * | 2016-03-29 | 2017-10-05 | Ridgeview Instruments Ab | Method for the detection of molecules being in close proximity |
Also Published As
Publication number | Publication date |
---|---|
JP2007523344A (en) | 2007-08-16 |
CN1922483B (en) | 2012-02-29 |
BRPI0507855A (en) | 2007-07-10 |
BRPI0507855B1 (en) | 2016-02-16 |
AU2005215573A1 (en) | 2005-09-01 |
EP1723411B1 (en) | 2013-08-07 |
AU2005215573B2 (en) | 2010-09-23 |
US7867753B2 (en) | 2011-01-11 |
JP4621693B2 (en) | 2011-01-26 |
CN1922483A (en) | 2007-02-28 |
CA2556686A1 (en) | 2005-09-01 |
US20070160979A1 (en) | 2007-07-12 |
SE0400403D0 (en) | 2004-02-20 |
WO2005080967A8 (en) | 2005-11-03 |
EP1723411A1 (en) | 2006-11-22 |
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