WO2001046382A2 - Cassette de separation de particules et procedes associes - Google Patents
Cassette de separation de particules et procedes associes Download PDFInfo
- Publication number
- WO2001046382A2 WO2001046382A2 PCT/US2000/034505 US0034505W WO0146382A2 WO 2001046382 A2 WO2001046382 A2 WO 2001046382A2 US 0034505 W US0034505 W US 0034505W WO 0146382 A2 WO0146382 A2 WO 0146382A2
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- membrane
- sample
- platform
- opening
- absorbent material
- Prior art date
Links
- 238000000034 method Methods 0.000 title claims description 23
- 239000002245 particle Substances 0.000 title description 19
- 238000000926 separation method Methods 0.000 title description 8
- 239000012528 membrane Substances 0.000 claims abstract description 169
- 239000012472 biological sample Substances 0.000 claims abstract description 15
- 230000002093 peripheral effect Effects 0.000 claims abstract description 9
- 239000000523 sample Substances 0.000 claims description 118
- 239000002250 absorbent Substances 0.000 claims description 85
- 230000002745 absorbent Effects 0.000 claims description 85
- 239000007788 liquid Substances 0.000 claims description 38
- 239000000463 material Substances 0.000 claims description 30
- 239000003153 chemical reaction reagent Substances 0.000 claims description 19
- 238000004458 analytical method Methods 0.000 claims description 17
- 230000001413 cellular effect Effects 0.000 claims description 14
- 238000009736 wetting Methods 0.000 claims description 14
- 230000003287 optical effect Effects 0.000 claims description 11
- 230000013011 mating Effects 0.000 claims description 9
- 238000004163 cytometry Methods 0.000 claims description 7
- 238000003556 assay Methods 0.000 claims description 6
- 102000004190 Enzymes Human genes 0.000 claims description 3
- 108090000790 Enzymes Proteins 0.000 claims description 3
- 150000007523 nucleic acids Chemical class 0.000 claims description 3
- 102000039446 nucleic acids Human genes 0.000 claims description 3
- 108020004707 nucleic acids Proteins 0.000 claims description 3
- 210000004027 cell Anatomy 0.000 description 35
- 239000011148 porous material Substances 0.000 description 13
- 230000000994 depressogenic effect Effects 0.000 description 10
- 210000000601 blood cell Anatomy 0.000 description 8
- 230000009977 dual effect Effects 0.000 description 6
- 230000002159 abnormal effect Effects 0.000 description 4
- 239000012491 analyte Substances 0.000 description 4
- 239000000203 mixture Substances 0.000 description 4
- 229920006395 saturated elastomer Polymers 0.000 description 4
- 239000003814 drug Substances 0.000 description 3
- 229940079593 drug Drugs 0.000 description 3
- 239000004033 plastic Substances 0.000 description 3
- 238000004166 bioassay Methods 0.000 description 2
- 238000006243 chemical reaction Methods 0.000 description 2
- 238000004891 communication Methods 0.000 description 2
- 239000012530 fluid Substances 0.000 description 2
- 230000003993 interaction Effects 0.000 description 2
- 238000002955 isolation Methods 0.000 description 2
- 239000003550 marker Substances 0.000 description 2
- 102000005962 receptors Human genes 0.000 description 2
- 108020003175 receptors Proteins 0.000 description 2
- 238000012552 review Methods 0.000 description 2
- 238000012216 screening Methods 0.000 description 2
- XUIMIQQOPSSXEZ-UHFFFAOYSA-N Silicon Chemical compound [Si] XUIMIQQOPSSXEZ-UHFFFAOYSA-N 0.000 description 1
- 230000001594 aberrant effect Effects 0.000 description 1
- 238000002835 absorbance Methods 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 230000004071 biological effect Effects 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 229920002301 cellulose acetate Polymers 0.000 description 1
- 239000000470 constituent Substances 0.000 description 1
- 238000011109 contamination Methods 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 239000000975 dye Substances 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 238000001704 evaporation Methods 0.000 description 1
- 238000000684 flow cytometry Methods 0.000 description 1
- 239000007850 fluorescent dye Substances 0.000 description 1
- 239000012478 homogenous sample Substances 0.000 description 1
- 238000007373 indentation Methods 0.000 description 1
- 238000001746 injection moulding Methods 0.000 description 1
- 238000003780 insertion Methods 0.000 description 1
- 230000037431 insertion Effects 0.000 description 1
- 102000027411 intracellular receptors Human genes 0.000 description 1
- 108091008582 intracellular receptors Proteins 0.000 description 1
- 230000001788 irregular Effects 0.000 description 1
- 239000003446 ligand Substances 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 239000002991 molded plastic Substances 0.000 description 1
- 230000000877 morphologic effect Effects 0.000 description 1
- 239000008055 phosphate buffer solution Substances 0.000 description 1
- 229920000515 polycarbonate Polymers 0.000 description 1
- 239000004417 polycarbonate Substances 0.000 description 1
- 229920000728 polyester Polymers 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 238000012545 processing Methods 0.000 description 1
- 230000001737 promoting effect Effects 0.000 description 1
- 230000000717 retained effect Effects 0.000 description 1
- 229910052710 silicon Inorganic materials 0.000 description 1
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- 230000000087 stabilizing effect Effects 0.000 description 1
- 238000010186 staining Methods 0.000 description 1
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- 239000000725 suspension Substances 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- 229910052724 xenon Inorganic materials 0.000 description 1
- FHNFHKCVQCLJFQ-UHFFFAOYSA-N xenon atom Chemical compound [Xe] FHNFHKCVQCLJFQ-UHFFFAOYSA-N 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12M—APPARATUS FOR ENZYMOLOGY OR MICROBIOLOGY; APPARATUS FOR CULTURING MICROORGANISMS FOR PRODUCING BIOMASS, FOR GROWING CELLS OR FOR OBTAINING FERMENTATION OR METABOLIC PRODUCTS, i.e. BIOREACTORS OR FERMENTERS
- C12M47/00—Means for after-treatment of the produced biomass or of the fermentation or metabolic products, e.g. storage of biomass
- C12M47/02—Separating microorganisms from the culture medium; Concentration of biomass
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N15/00—Investigating characteristics of particles; Investigating permeability, pore-volume or surface-area of porous materials
- G01N15/06—Investigating concentration of particle suspensions
- G01N15/0606—Investigating concentration of particle suspensions by collecting particles on a support
- G01N15/0618—Investigating concentration of particle suspensions by collecting particles on a support of the filter type
- G01N15/0625—Optical scan of the deposits
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N1/00—Sampling; Preparing specimens for investigation
- G01N1/28—Preparing specimens for investigation including physical details of (bio-)chemical methods covered elsewhere, e.g. G01N33/50, C12Q
- G01N1/40—Concentrating samples
- G01N1/4077—Concentrating samples by other techniques involving separation of suspended solids
Definitions
- the invention relates generally to an apparatus and methods for separating particles
- the invention relates to s ' eparating particles from a mixture using a substantially flat membrane
- cells are separated from a sample mixture and examined to
- biological specimens such as flow cytometers, automated blood cell analyzers, and blood cell
- differential classifiers are commonly used.
- a flow cytometer is an instrument that hydrodynamically focuses a fluid suspension of
- the flow cytometer measures optical interactions, such as, absorption, scatter, and fluorescence, between the light and the cells.
- cytometers permit the study of living, unstained, cells in addition to those which have been
- Flow cytometry techniques enable certain cellular constituents, particularly those on the cell surface, to be quantitatively characterized at rates of a
- Blood cell analyzers typically consist of a computerized microscope that classifies
- blood cell analyzers identify and count abnormal cells
- a blood cell differential classifier typically consists of a computer-controlled microscope
- a light source such as a xenon arc lamp, illuminates cells and the classifier uses various sensors, such as a silicon photodiode array, to
- the present invention solves the problem of rapid, efficient particle separation in a
- a separation device having a platform upon which is mounted a
- the sample is placed on the platform, which preferably has a sink for containing the sample, and the sample is drawn through the membrane, preferably by an
- a device of the invention allows rapid processing of a sample, retaining primarily those particles desired for analysis on the membrane surface.
- the membrane pore size regulates capture of
- the invention provides a cassette comprising a platform, a membrane,
- the cassette may be engaged with a
- biological sample has a platform defining a first opening, a membrane, and a mount defining a
- the mount and the platform engage in a peripheral interference fit such that the membrane is stretched radially between the two openings.
- the platform has, on one side, a sink capable of containing a sample, and a cavity for containing an absorbent material on a second side.
- a sink capable of containing a sample
- a cavity for containing an absorbent material on a second side.
- first opening is cylindrical, and the platform has a raised ring on the second side that
- An annular depression concentrically surrounds the
- a preferred mount has a flange for a radial interference mating with the raised ring on the platform.
- the flange concentrically surrounds the second opening.
- the platform has a plurality of posts on the second surface, and the mount has a plurality of apertures for receiving the posts when the mount engages the platform.
- the posts are on the mount and the apertures are on the platform.
- a membrane for use in a device of the invention may be any membrane sufficient for
- the membrane may be track-etched or may have a diameter larger than the opening in the platform, the opening in the mount, or the annular
- a highly-preferred membrane has at least three detectable coordinate
- the coordinate points may be optical markers, such as fluorescent markers and other markers detectable by laser scanning cytometry or
- absorbent material for use in a device of the invention may be any material.
- a suction or vacuum device may be used as an alternative to, or in addition to, the absorbent
- a cartridge that has a housing adapted to contain the device.
- the cartridge may have reagent wells capable of containing reagents used in a bioassay of particles on the membrane.
- a bioassay may be automated in, for
- Cartridges may be reusable or recyclable, or may be
- a device for separating a component from a biological sample has a platform defining a first opening, a membrane, a mount, and a trough.
- platform defines a cavity that contains an absorbent material contained within the cavity.
- mount defines a second opening that mates with the first opening.
- the trough is provided for introducing a liquid to a
- the trough contains the absorbent material, and/or a secondary absorbent material is in contact with the absorbent material. Also, in some embodiments, a third opening in the
- methods of the invention provide an assay for
- sample is applied, either before or after application of reagents, to a device as described above in order to capture at least a portion of the sample on the membrane.
- the sample components that are captured on the device membrane then are analyzed for at least one cellular characteristic, for
- a liquid can be used
- Methods of the invention preferably comprise detecting an optical property (e.g., density,
- methods of the invention may be used to measure or characterize cell-surface
- Figure 1 depicts a schematic exploded perspective view of one embodiment of a cassette
- Figure 2 A depicts a schematic top view of the embodiment shown in Figure 1;
- Figure 2B depicts a schematic sectional view taken along line A-A of the embodiment
- Figure 2A depicts a schematic top view of one embodiment of a cartridge of the invention
- Figure 4 depicts a schematic perspective view of the cassette of Figure 1 in association
- Figure 5 depicts a schematic exploded perspective view of one embodiment of a cassette
- Figure 6 A depicts a perspective view of the top side of a dual opening housing of the
- Figure 6B depicts a perspective view of the bottom side of a dual opening housing of the
- Figure 7 depicts a view of a retainer of the embodiment of Figure 5;
- Figure 8 A depicts a perspective view of the top of the cartridge of Figure 5 with the cassette of Figure 5 removed;
- Figure 8B depicts a perspective view of the bottom of the cartridge of Figure 5;
- Figure 9A depicts a schematic exploded perspective view of a cassette that is similar to that shown in Figure 1 and the cartridge that is shown in Figure 5;
- Figure 9B depicts a schematic sectional view of the cassette of Figure 9A taken along a
- Figure 10 depicts a schematic exploded perspective view of a cassette that is similar to that shown in Figure 5 and the cartridge that is shown in Figure 5.
- Apparatus and methods of the invention provide for rapid and accurate sample
- the invention is especially useful in
- a device of the invention has a platform with an opening over which a membrane is
- the platform mounted by a peripheral interference fit between the platform and a mount.
- the mount On one side, the
- the platform has a sink for applying the sample to membrane. On the other side, the platform has a
- the contents of the membrane are reacted with one or more reagents (e.g. , dyes,
- Laser scanning cytometers typically require a flat surface to efficiently analyze a sample.
- the invention combines an ability to separate fractions of a sample through a membrane with an
- apparatus and methods, according to the invention provide a flat
- the invention provides a cassette that holds a membrane flat for
- the cassette in certain embodiments, fits into a cartridge
- an assay can be conducted in an automated, high through-put configuration.
- the reagents for
- a fluorescent marker for example, a fluorescent marker
- sample is mixed and applied to the membrane, capturing at
- one embodiment of the invention has a housing 2, a retainer 4, and a membrane 6.
- the underside of the housing 2 defines a cavity 24 and a through-hole 28.
- the through-hole 28 has a diameter of 10 mm. Disposed concentrically about the through-hole 28
- through-hole 24 are a raised ring 32 and a depressed annular region 30. Projecting from a floor
- the mounting posts 16, 18, 20, 22 each have a mounting post 16 18, 20, 22.
- the mounting posts 16, 18, 20, 22 are shown arranged in a generally rectangular configuration with the same
- a membrane 4 fits over the through-hole 28, raised ring 32, and depressed annular region 30 and contacts the housing 2.
- the membrane 6 is slightly larger than the diameter of the
- the membrane 6 is about 0.04 inches (about 0.1 cm) larger than the diameter of the depressed annular region 30 (which can be about 0.666
- the membrane 6 can be manufactured from a plastic, such as polycarbonate or polyester.
- the membrane 6 can be track
- the pores through the membrane 6 are
- the concentration in the sample of the cells is the concentration in the cells or particles to be captured on the membrane, the concentration in the sample of the cells
- particles in the sample to be captured can be considered when choosing a pore size and/or
- an appropriate pore size is chosen to
- the pores through the membrane have about a 5 ⁇ m diameter, and the membrane
- a retainer 4 secures and stretches the membrane 6 against the housing 2.
- the mounting apertures are located on the housing and the mounting posts are located on the retainer.
- the retainer 4 is forced down onto the mounting posts 16, 18, 20, 22 with,
- the membrane 6 can have a flatness tolerance of less than about 200 ⁇ m, preferably less than
- the surface of the membrane 6 lies between two planes that are separated by less than about 200 ⁇ m, preferably less
- the flatness tolerances mentioned above can be achieved, for example, over about a 10 mm diameter membrane.
- membrane 6 is of a shape and/or size so that the membrane 6 does not interfere with mounting
- a sample cavity 38 defined by the housing 2 is located on the side of the housing 2 opposite the cavity 24 and floor 42.
- the sample cavity 38 in this embodiment, is not as deep as the cavity 24.
- the sample sink 40 can hold approximately 2 ml of a liquid. Depending upon the embodiment, a greater or lesser amount of liquid can be held by a sample sink. Typically, an
- absorbent reservoir 54 ( Figure 4) is included in the cavity 24 that will pull fluid in the sample
- the absorbent reservoir 54 can be constructed
- the absorbent reservoir 54 is adhered to, or in
- the assembled cassette 44 can be retained within a cartridge 52.
- One manner to retain the cassette 44 is through the use of four spring fingers 36, only one
- the cartridge 52 can be made from, for example, a plastic.
- the cartridge 52 can contain sample-holding and/or reagent wells 46, 48 and/or a disposal area
- a sample for example,
- reagent 48 or contained in the sample sink 40, is combined with reagent(s) (for example, antibodies tagged with fluorochromes).
- the reagent(s) can be contained in a reagent well 46, 48 or can be
- the reaction(s) between the reagent(s) are at least sufficiently complete to obtain a reading, if the reaction(s) were accomplished outside of the sample sink 40, the reacted sample is applied to the membrane 6 in the sample sink 40.
- reservoir 54 pulls at least a portion of the sample through the membrane as described above.
- the membrane region is then positioned in the path of an objective lens of an optical reader, such as
- the captured sample on the membrane 6 is analyzed.
- the laser scanner typically will have a
- the depth of focus requirement for some laser scanning optics is the depth of focus requirement.
- the flatness tolerance of the membrane described above is desirable for ensuring that the surface of the membrane where sample is captured is within the laser scanning
- the membrane can include at least three detectable coordinate points in order to facilitate
- markers such as fluorescent markers, can be observable with the laser scanning
- the three points define a plane of the surface of the membrane, and the laser scanning cytometer can use this plane for the purposes of analyzing and obtaining location data
- substantially homogeneous flow through the membrane is facilitated.
- uneven flow through the membrane occurs, for example, due to the fibrous nature of an absorbent reservoir. Liquid will
- uneven distribution of analyte from the sample on the membrane may cause aberrant measurements due to greater than expected densities of analyte on the membrane in areas of high flow through the membrane.
- the absorbent reservoir typically is not wet through the membrane, but, rather, is
- a cartridge 60 in relation to a cartridge 60 (described more fully below), includes a trough 160 in which the absorbent reservoir 54 sits.
- the absorbent reservoir 54 rests on a trough
- a wetting aperture 164 aligns with the slot 166, and the retainer 4 does not interfere with
- reservoir 162 contacts the absorbent reservoir 54 through the notch 170 and is located in a cutout in the trough 160.
- the entire assembled cassette 144 and trough 160 fits within the cartridge
- a volume of a liquid for example, but without limitation, a phosphate buffer solution
- absorbent reservoir 54 begins to shed liquid over at least some of its surface area. Because of the close proximity between the membrane 6 and the absorbent reservoir 54, the liquid shed by the
- absorbent reservoir 54 fills a region 172 (best shown in Figure 9B) between the membrane 6 and absorbent reservoir 54 (for example, through capillary action), wetting substantially all of the
- the region 172 typically is the area where the membrane 6
- This contact can be
- an absorbent material 54 that is in substantially intimate contact with the membrane 6 can touch the membrane 6 such that the space between the membrane 6 and the absorbent reservoir 54 can be irregular. Additionally, capillary forces fill substantially all of the
- the secondary absorbent reservoir 162 which contacts the absorbent reservoir 54 through the notch 170, contains sufficient absorbing character (exercised via the notch 170 and
- reservoir 54 is saturated. This configuration allows for the absorbent reservoir 54 to saturate and
- reservoir configurations can be used if they produce a result that involves both filling the region
- the membrane particularly in a substantially homogeneous manner.
- the absorbent for example, the absorbent
- reservoir could be a single unit composed of two areas, each with a different absorbing character.
- the sample when a sample is applied to the sample sink, the sample can flow through the membrane in a substantially even fashion. Additionally, because the secondary
- absorbent reservoir 162 is not fully saturated (i.e., has the capacity to absorb additional liquid),
- the size of the notch 170 is one way to control how much liquid saturates the secondary absorbent reservoir 162 as the absorbent reservoir 54
- an analysis device that includes a
- the sample is placed into one of the wells, and the cartridge with
- reagent(s) such as a label
- the laser scanning cytometer can detect.
- the sample can be stained with a
- fluorescent dye Multiple labels can be used at once to detect multiple properties of the sample.
- a sample can be analyzed for a nucleic acid present in the sample, an enzyme
- a receptor present in the sample present in the sample, a receptor present in the sample, and/or a cell type present in the sample.
- the wells can contain various substances, such as a drug, for application to the sample.
- the sample may, for example, be stained with a different label if exposed to a drug than if it is unexposed to a drug.
- competition and/or kinetic studies can be performed. Other
- sample is applied to the sample sink, captured on the membrane, and detected.
- the procedure can be fully automated.
- the analysis device can locate the
- cassettes according to the invention have a particular flatness tolerance, such as the ones described above, the laser
- scanning cytometer can directly analyze the sample as captured on the membrane.
- cassette 79 has two through-holes 68a, 68b disposed within the housing 62.
- 66b are held over the through-holes 68a, 68b with retainers 64a, 64b. Disposed concentrically about the through-holes 68a, 68b are raised rings 112a, 112b and depressed annular regions 110a,
- mounting posts 102a, 102b, 104a, 104b, 106a, 106b, 108a, 108b Projecting from a floor of the cavity are mounting posts 102a, 102b, 104a, 104b, 106a, 106b, 108a, 108b.
- the mounting posts 102a, 102b, 104a, 104b, 106a, 106b, 108a, 108b each
- posts 102a, 102b, 104a, 104b, 106a, 106b, 108a, 108b are shown arranged in a generally square
- the membranes 66a, 66b fit over the through-holes 68a, 68b, raised rings 112a, 112b, and
- the membranes 66a, 66b are slightly larger than the diameters of the depressed annular regions 110a, 110b.
- 66a, 66b in this embodiment can have the same properties, can be used in a similar manner, and
- Retainers 64a, 64b stretch the membranes 66a, 66b and secure them against the housing 62.
- Mounting apertures 92a, 92b, 94a, 94b, 96a, 96b, 98a, 98b through the retainers 64a, 64b are provided in the corners of each of the retainers 64a, 64b.
- the mounting apertures 92a, 92b, 94a, 94b, 96a, 96b, 98a, 98b are slightly smaller in diameter than the mounting posts 102a, 102b, 104a, 104b, 106a, 106b, 108a, 108b.
- a retainer is a single piece but has the two apertures as well as the surrounding structures for radially stretching the two membranes.
- housing 62, retainers 64a, 64b and membranes 66a, 66b are assembled into a unit in a similar
- each membrane 66a, 66b forms the floor of a sample sink, and the walls of the apertures 118a,
- Each mating portion 78 has a
- each spring finger 76 is resilient and is moved slightly towards the center of the housing 62 as the spring finger 76 enters the mating portion 78 to slide the leading edge of the spring finger 76 past the mating portion 78 lip.
- the spring finger 76 due to its resiliency, returns to its starting position, away from the center of the housing 62, locking the housing 62 to the cartridge 60.
- the cartridge 60 itself (shown, for example, in Figures 8A and 8B) has multiple sample holding and/or reagent wells 86, 88 (only some being labeled for clarity) and a disposal area 80.
- cartridge 60 has stabilizing bands 122 (only one being labeled for clarity) that keep the cartridge
- this cartridge 60 in combination with the dual sample sink cassette 79, allows for two samples to be processed simultaneously.
- multiple sample sinks in certain embodiments, multiple sample sinks
- cartridge and cassette assembly is suitable for use with an automated, preprogrammed analyzer as
- reservoir and a membrane with a liquid such as that shown in and described for Figures 9A and 9B, is applicable to dual sample well and multiple sample well embodiments.
- FIG 10 a slightly modified version 179 of the embodiment 79 shown in Figures 5-8B has a
- reservoir 74a, 74b are filled with a liquid to facilitate a substantially
- liquid is provided through either one of or both of two wetting apertures 264a, 264b in the housing 62.
- Each wetting aperture is provided through either one of or both of two wetting apertures 264a, 264b in the housing 62.
- 264a, 264b aligns with a corresponding slot 266a, 266b molded into one of two troughs 260a,
- the wetting apertures 264a, 264b are located along a midline of the housing 62.
- One region (that is ultimately filled with liquid) is formed between one membrane that is aligned with one absorbent reservoir (i.e., there are two regions, one formed between each one of
- a single-piece secondary absorbent reservoir 262 contacts both absorbent reservoirs 74a, 74b through the two notches
- the secondary absorbent reservoir 262 typically does
- Liquid is dropped through the wetting apertures 264a, 264b and into the slots 266a, 266b
- Fingers 272a protruding from the troughs 260a, 260b (only one finger is labeled for
- the cassette 179 with the cartridge 60 are arranged such that slots are formed between the trough fingers 272a to accommodate the spring fingers 76 as they pass through the troughs 260a, 260b and mate with the mating portions 78.
- the troughs can be a single
- the secondary absorbent reservoir can be two pieces or
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Abstract
L'invention se rapporte à un dispositif permettant de séparer un composant d'un échantillon biologique et comportant une plate-forme, une membrane et un organe de montage. La plate-forme définit une première ouverture et l'organe de montage définit une seconde ouverture. L'organe de montage et la plate-forme s'accouplent par un ajustement avec serrage périphérique de sorte que la membrane est étirée radialement entre la première et la seconde ouverture.
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US46764599A | 1999-12-21 | 1999-12-21 | |
US09/467,645 | 1999-12-21 |
Publications (2)
Publication Number | Publication Date |
---|---|
WO2001046382A2 true WO2001046382A2 (fr) | 2001-06-28 |
WO2001046382A3 WO2001046382A3 (fr) | 2002-05-02 |
Family
ID=23856537
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
PCT/US2000/034505 WO2001046382A2 (fr) | 1999-12-21 | 2000-12-19 | Cassette de separation de particules et procedes associes |
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Country | Link |
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WO (1) | WO2001046382A2 (fr) |
Cited By (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2010040371A1 (fr) * | 2008-10-07 | 2010-04-15 | Bio Explorer B.V. | Dispositif et procédé d'analyse automatique de micro-organismes dans un échantillon |
WO2011099862A1 (fr) * | 2010-02-12 | 2011-08-18 | Dutch Water Technologies B.V. | Module de préparation automatique d'échantillons toxicologiques fluides, système d'analyse automatique et procédé pour son utilisation |
WO2011099861A1 (fr) * | 2010-02-12 | 2011-08-18 | Dutch Water Technologies B.V. | Module de préparation automatique d'échantillons fluides, système d'analyse automatique et procédé pour son utilisation |
CN112973458A (zh) * | 2021-02-08 | 2021-06-18 | 中国科学院近代物理研究所 | 离子径迹多孔膜及其物理制备方法与应用 |
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US5891394A (en) * | 1994-11-17 | 1999-04-06 | Chemunex | Apparatus for rapid and ultrasensitive detection and counting of microorganisms by fluorescence |
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WO2010040371A1 (fr) * | 2008-10-07 | 2010-04-15 | Bio Explorer B.V. | Dispositif et procédé d'analyse automatique de micro-organismes dans un échantillon |
US11226347B2 (en) | 2008-10-07 | 2022-01-18 | Biotrack Holding B.V. | Method for simultaneously and automatically analyzing microorganisms in a sample using filter cytometry |
WO2011099862A1 (fr) * | 2010-02-12 | 2011-08-18 | Dutch Water Technologies B.V. | Module de préparation automatique d'échantillons toxicologiques fluides, système d'analyse automatique et procédé pour son utilisation |
WO2011099861A1 (fr) * | 2010-02-12 | 2011-08-18 | Dutch Water Technologies B.V. | Module de préparation automatique d'échantillons fluides, système d'analyse automatique et procédé pour son utilisation |
US10280471B2 (en) | 2010-02-12 | 2019-05-07 | Biotrack Holding B.V. | Methods for detecting micro-organisms and/or biological substances in a fluid |
CN112973458A (zh) * | 2021-02-08 | 2021-06-18 | 中国科学院近代物理研究所 | 离子径迹多孔膜及其物理制备方法与应用 |
CN112973458B (zh) * | 2021-02-08 | 2022-12-27 | 中国科学院近代物理研究所 | 离子径迹多孔膜及其物理制备方法与应用 |
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