WO1996040408A1 - Method and apparatus for solid-liquid separation - Google Patents

Method and apparatus for solid-liquid separation Download PDF

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Publication number
WO1996040408A1
WO1996040408A1 PCT/US1996/010018 US9610018W WO9640408A1 WO 1996040408 A1 WO1996040408 A1 WO 1996040408A1 US 9610018 W US9610018 W US 9610018W WO 9640408 A1 WO9640408 A1 WO 9640408A1
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WO
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Patent type
Prior art keywords
fluid
collection
solid
fibers
collection arrangement
Prior art date
Application number
PCT/US1996/010018
Other languages
French (fr)
Inventor
Raouf A. Guirguis
Original Assignee
La Mina, Inc.
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    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01DSEPARATION
    • B01D35/00Other filtering devices; Auxiliary devices for filtration; Filter housing constructions
    • B01D35/10Brush filters Rotary brush filters
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01DSEPARATION
    • B01D2201/00Details relating to filtering apparatus
    • B01D2201/40Special measures for connecting different parts of the filter
    • B01D2201/4084Snap or Seeger ring connecting means

Abstract

The present invention is a method and apparatus for separating a solid phase from a liquid phase. The apparatus includes a collection site formed of fibers.

Description

METHOD AND APPARATUS FOR SOLID-LIQUID SEPARATION

TECHNICAL FIELD OF THE INVENTION

The present invention is directed to an apparatus and method for separating two phases, solid and liquid, from a suspension.

BACKGROUND OF THE INVENTION

Methodologies such as immunocytochemistry and image analysis require preparations that are fast, reproducible, biohazard-free and inexpensive. The accuracy of a diagnosis and the preparation of optimally interpretable specimen slides may depend both upon adequate patient sampling and on culture or slide preparation procedures.

There currently exists a need to concentrate molecular components of urine and separately concentrate the urinary sediments for diagnosing the presence of cancer at an early stage in the development of the cancer. For example, excessive number of red blood cells may indicate the presence of a tumor, stones or inflammation. Excessive number of leukocytes may indicate infection or other inflammatory disease. In contrast to the hypocellular nature of normal urine, neoplastic cells (e.g., transitional, squamous an columnar cells) are shed more frequently in malignant conditions of the bladder epithelium.

Under normal conditions, urine contains a small number of cells and other particulate matter shed from the entire length of the urinary tract. These materials are usually known as urinary sediments. Typical urinary sediments consist of red blood cells, white blood cells, epithelial cells, casts, mucus and crystals. In addition, sporatic urinary sediment such as bacteria, yeast parasites and spermatozoa occur in patients suffering from various types of disorders or engaging in particular activities.

Examination of urinary sedimentation is a routine procedure in urinalysis. With disease, these cells as well as other formed elements are often increased and may indicate tumor, stones or inflammation. Excessive number of leukocytes may indicate infection or other inflammatory disease. In contrast to the hypocellular nature of normal urine, neoplastic cells (e.g., transitional, squamous and columnar cells) are shed more frequently in malignant conditions of the bladder epithelium. It is therefore desirable to provide an easy to handle disposable apparatus and method which transports a fluid sample such as urine through a specific element for capturing urinary sediments and particulate matter from the urine. This allows more sensitive cancer detection from the sample, provides that the test specimen can be compactly stored for a period of time in concentrated form, and allows testing to be performed quickly and accurately by distal testing facilities.

The analysis of complex mixtures often requires that they first be separated into their components. Because of the similarity in the chemistry of the analytes in a complex mixture and even where analytes in the sample are few, they can be so overlapping in properties that probes or methods of adequate selectivity are lacking and separation is required. In these cases, separation is an essential part of the analytical procedure. Even when the mixture contains species which are distinctly different, there can be other compelling reasons for making separation a part of the total analytical procedure as, for example, speed of analysis. Should one or more of the various determinations of separation be time consuming, then the total time to analyze a single sample can be considerable. A preliminary separation, on the other had, if it is fast enough, opens up the possibility of applying nonselective measurement techniques to the separated components. If the measurement step matches the speed of the separation, the coupling of the two can provide an effective solution to the time problem. Modern day chromatography exemplifies this successful marriage of separation and essentially instantaneous measurement of the separated components.

Bioseparation methods used for purification of organic (i.e., carbohydrates, proteins, lipids, hormones and vitamins) and inorganic (i.e., metals and ions) compounds are typically based on chromatography techniques. Resin-based gel chromatography uses the mechanisms of ion exchange, ion exclusion, ligand exchange, reversed phase, normal phase and high affinity. These multiple modes of interaction offer a unique ability to separate compounds based on their charge (i.e., positive, negative and neutral charges), solubility (i.e., hydrophobicity and hydrophilicity), specific ligand or chemical group interaction (e.g., enzymes) and antigen antibody reactions.

Chromatography today exists in such a variety of forms that defining it in a way that is concise as well as comprehensive is virtually impossible. It should be recognized that what is called the mobile phase in chromatography can be as gas, a liquid or a supercritical fluid and it may contain organic or inorganic molecules or other modifiers necessary for the separation process. A definition of chromatography should accommodate all the manifold forms of the stationary phase as well. Further, an adequate definition should convey some idea of the variety of ways in which the two phases are presented to each other as, for example, in columns, as a thin layer on a plate, as a paper strip suspended in a reservoir of solvent, etc. The development of gas chromatography has provided a rapid, selective and sensitive means of analyzing complex mixtures of closely similar, volatile organic compounds. Later, important . advances in the use of liquid mobile phases extended chromatography to the whole range of organic materials whether they were volatile or not. In this regard, the distribution of solutes between phases, as well as being of great interest, is one of the core concepts of chromatography and success in the practice of chromatography depends to a great extent on the fundamental knowledge of these distribution equilibria and on the ability to influence them. The analytical chemistry of inorganic species is in large part the analysis of electrolytes in aqueous solution and to this, ion exchange has brought considerable benefits. Many ion exchange chromatographic methods were devised that provided clean separations which were effective, but were used mostly as an adjunct to existing wet chemical methods in order to solve interference and matrix problems. As a result, the speed of the analysis was often determined by the relatively slow wet chemical method. Today, the chromatographic analysis of ionic materials is widely applied and rapidly expanding. The number of species that may be determined continues to grow, as does the number of areas of science and technology where liquid chromatography plays an important role. The table below shows a sampling of the breadth of application of chromatography at the present time. Types of Samples Analyzed by Chromatography

Acid rain

Analgesics Chemicals

Detergents

Drinking water

Fermentation broths Fertilizers

Foods and Beverages

High-purity water

Ores Pesticides

Pharmaceuticals

Physiological fluids

Plating baths Protein hydrolysates

Pulping liquors

Soil and plant extracts

Waste water

Immunoassay works upon the simple principle of the specific recognition of a ligand, e.g., an antigen, for its complementary pair, e.g., an antibody. Thus, specific antigen detection and quantification requires an antibody which recognizes the uniqueness of an antigen. The antigen binding site of antibodies recognizes about six amino acids or their equivalent in mass. One unique binding site serves as an identifying marker for that protein.

When a definitive antibody for a given antigen is available, it is used to identify the antigen in the sample mixture. Once the antibody combines with the antigen, a means is needed to recognize the resulting complex. There presently exists a need to concentrate antigens from volumes fluid when the antigen is not present in measurable quantities in specific fluid volumes. It is generally necessary in diagnosing and testing for many disease to collect biological fluids from a patient. Although blood, urine and cerebrospinal fluids are the most common specimens received for diagnosis, other fluids such as seminal, synovial pleural, pericardial, peritoneal, amniotic and sweat are associated with specific condition and diseases. It is important during the collection and handling of biological fluid specimens that specimen deterioration, contamination and the spread of any infection from the specimen be minimized. While samples are commonly collected in large containers, the actual testing is commonly conducted with relatively small amounts of sample, around 0.2-0.5 ml in volume. Thus, because of the small test quantity, some analyses, such as for cancer producing antigen, can only be ascertained after the cancer is in an advanced or late tumor stage. The rest of the body fluid sample is used for further testing, frozen, or thrown away.

Additional problems occur in shipment when dealing with urine samples because of the relatively large volume of fluid involved in the collection of specimen samples. There is also the risk of sample deterioration because of the relatively short sample shelf life of urine unless kept in specific temperature conditions and/or treated with a variety of preservative. In addition, there is also the potential for specimen damage or spillage during the collection and/or shipment process as well as the potential for destruction of certain molecular components of the specimen such as antigens and cellular materials such as urinary sediments because the packaging does not protect the urine from possible chemical changes in its different components which will negate the test results or result in false date being obtained when the specimen is tested.

SUMMARY OF THE INVENTION The present invention relates to an apparatus and method for separating a solid phase from a liquid phase, and a separation apparatus which can be removably detached from a collection container for additional processing. The collection container permits the separate collection of both a solid phase and a liquid phase. Passage of a solid-liquid suspension from a collection container to the solid-liquid separation apparatus may be carried out without pouring or pipetting.

The present invention is directed to a solid phase and/or liquid phase collection and distribution apparatus which can be disassembled to allow transfer of the solid phase from the device to additional processing apparatuses. It is an object of the invention to provide a method for collecting a solid or liquid phase and transferring the collected solid or liquid phase to an apparatus for additional processing, including, but not limited to detection, diagnosis, and/or preservation process steps.

The present invention is also directed to a solid-liquid separation kit containing the apparatus described above, and optionally, including an apparatus removably mounted to a fluid collection cup. The present invention also includes a method for separating a solid phase from a liquid phase comprising passing a liquid sample or suspension having a solid phase and a liquid phase through a fibrous collection arrangement having a first fluid flow path adapted to collect the solid phase in the fibrous collection arrangement which fibrous collection arrangement is positioned across the first fluid flow path, and optionally, a second fluid flow path adapted to pass the liquid phase. The solid phase is deposited on or collected in a collection site of the fibrous collection arrangement. It is intended that the present invention is not to be limited by the type of solid or liquid phase which is to be collected or processed.

Accordingly, a principal aspect of the invention is that it provides for increased speed of examination accompanied by reduced expense and increased accuracy, since analysis of a collected sample and harvesting of selective components contained therein, is more efficient. Furthermore, diagnostics can be performed on site, contemporaneously, or shortly after collection. In addition, with respect to microscopic observation, laboratory personnel waste less time examining each microscope slide, while viewing material free of interference. Since the present invention enhances the presentation of particles or cells, another significant aspect of the invention is to provide more consistent and reliable patient diagnosis.

Among other benefits, the instant invention decreases biohazard concerns since processing steps such as pouring and pipetting, which are prime sources of laboratory personnel biohazard exposure, are eliminated. Biohazard concerns are further decreased by the use of completely contained disposable components.

Moreover, because the process takes place in the cytology laboratory, slide or analyzer preparation and fixation are controlled by laboratory personnel and quality assurance is easily implemented.

The methods and apparatuses according to the invention may also be automated, or part of an automated system. 1 DESCRIPTION OF THE DRAWLNGS

Figure 1 is a cross sectional view of a solid-liquid separation apparatus according to the present invention.

Figure 2 is a cross sectional view of a syringe and solid-liquid separation 5 apparatus mounted on a collection cup.

Figure 3 is a cross sectional view of fluid flow paths in a solid-liquid separation apparatus according to the invention.

9 DETAILED DESCRIPTION OF THE INVENTION

The present invention includes an apparatus which includes a collection arrangement having fibers which capture a solid phase. More particularly, the present invention involves a separation apparatus comprising a housing having an inlet and

_-> defining at least one fluid flow path through the housing; and a collection arrangement disposed in the housing across the fluid flow path, the collection arrangement including a plurality of selectively receptive fibers for capturing a solid in a liquid suspension, said fibers having a supported end and a non-supported end. In a preferred embodiment, the

17 collection arrangement, or a portion of the apparatus, may be separated from the separation device for additional processing.

In an embodiment of the invention, the collection arrangement is adapted to remove or capture solid particles or cell matter suspended in a fluid phase, and may be

-">1 non-porous or porous, e.g., readily permitting the passage of the fluid phase therethrough.

The invention will now be described, in part, by reference to the exemplary embodiments shown in the Figures.

25 An exemplary embodiment according to the invention is shown in Figure 1. A separation device 10 may include a housing having an inlet 11 and an outlet 12, and defining at least one fluid flow path between the inlet and the outlet. A collection arrangement 20 may be positioned in the housing across at least one flow path between

29 the inlet 11 and the outlet 12.

The collection arrangement 20 is adapted to collect a solid phase contained in the liquid sample. Collection arrangement 20 is positioned across a first flow path, and may include a collection site 21 for the capture of the solid phase. The apparatus may also include at least one channel 22 adapted to permit fluid flow therethrough.

Another embodiment of the invention is shown in Figure 2. The separation device 10 is in communication with a specimen cup 30. The separation device 10 is connectable at inlet 11 to a port 32 in the specimen cup cover 31. The port 32 may, in turn, be in communication with a sample contained in the specimen cup 30 via elongated member 33. Inlet 11 of solid-liquid separation apparatus 10 may provide fluid communication with a source of liquid to be processed. Typically, the liquid to be processed may be in a container or the like. Exemplary containers include, but are not limited to a collection or specimen cup 30. In the illustrated embodiment of the assembly, inlet 11 of solid-liquid separation apparatus 10 is adapted to receive a port 32 in a cover 31 of cup 30. As shown in the illustrated embodiment, it may be desirable to include an elongated tube member 33 suitable for withdrawing fluid in the cup into the solid-liquid separation apparatus 10. Elongated member 33 may be an integral structure of the cup 30 (as shown), or may form an elongated inlet integral to the separation apparatus 10 (not shown). Figure 3 depicts an exemplary collection scenario in accordance with the invention. A liquid sample, or biological fluid, flows through collection device inlet 11. The sample passes across collection arrangement 20 and out through outlet 12. Typically, collection site 21 will capture desired matter within the liquid sample. Each of the elements of the invention will now be described in more detail below.

In an embodiment of the invention, the collection arrangement 20 includes a collection site 21. A collection arrangement refers to the non-porous or porous medium which captures or collects the solid matter. For example, a collection arrangement according to the invention may remove and/or concentrate cellular matter, such as cancer cells, from a biological fluid such as urine.

Collection site 21 preferably includes fibers, or fiber-like elements 23, typically positioned in a spaced relationship, which are capable of removing or capturing cellular material, solid particles or similar debris suspended in a fluid phase. If the collection apparatus and/or the fibers are porous, they will readily permit the passage of the fluid phase therethrough. The fibers or fiber-like elements may be single-stranded, multi- stranded, or in a loop configuration, among other structures.

In a more preferred embodiment, collection site 21 comprises a plurality of fibers or fiber-like elements 23 in which an end of the fiber or strand of the fiber is immobilized in or attached to a substrate 24. In the preferred embodiment, another end of the fiber or strand, i.e., an end distal from substrate 24, is preferably unattached, e.g., unsupported or free-floating. Alternatively, a fiber may be suspended between a first and a second substrate. A collection arrangement may be pre-formed, multi-layered, and/or may be treated to modify the surface of the medium. If a fibrous medium is used, the fibers may be treated either before or after forming the fibrous lay-up. It is preferred to modify the fiber surfaces before forming the fibrous lay-up because a more cohesive, stronger product is obtained after hot compression to form an integral filter element. The collection arrangement may include at least one of a prefilter element or layer and a filter element or layer. The collection arrangement may additionally include at least one element or layer to provide support, better drainage, and/or improved flow characteristics, such as more uniform flow distribution.

The collection arrangement may be configured as a flat sheet, a corrugated sheet, a web, or a membrane. The medium may be a depth filter, a single layer, or a composite of at least two fiber and/or membrane layers. Preferably, the collection arrangement is removable from the housing, but the medium may form an interference fit at its edges when assembled into the housing. The structure of collection site 21 is designed to separate a solid phase from the liquid phase. In a preferred embodiment, collection site 21 is adapted to remove or capture solid particles in a fluid phase, but may, as noted above, readily permit the passage of the fluid phase therethrough.

The fibers 23 can be formed of a variety of materials and be designed or treated to achieve a desired result. Formation of the fibers 23 may include, but is not limited to, the selection of specific materials from which to make the fibers; specified fiber shapes, cross sections or profiles; treatment of the fiber surface or subsurface; provision of surface features on the fibers; or any combination of the latter.

While the collection arrangement and/or fibers 23 can be produced from any 1 suitable material compatible with a biological fluid such as blood or urine, practical considerations dictate that consideration be given first to the use of commercially available materials. The medium of this invention may be formed, for example, from any synthetic polymer capable of forming fibers; in some embodiments of the 5 invention, the fibers may be capable of serving as a substrate for surface modification.

For example, the polymer should be capable of surface modification without the medium or fibers being significantly or excessively adversely affected by the surface modification process. Suitable exemplary polymers for use as the substrate may include, 9 but are not limited to, polyolefins, polyesters, polyamides, polysulfones, acrylics, polyacrylonitriles, polyaramides, polyarylene oxides and sulfides, and polymers and copolymers made from halogenated olefins and unsaturated nitriles. Examples include, but are not limited to, polyvinylidene fluoride, polyethylene, polypropylene, cellulose j acetate, and Nylon 6 and 66. Preferred polymers are polyolefins, polyesters, and polyamides.

Although the fibers of the porous medium may remain untreated, they are preferably treated to make them even more effective. For example, the fibers may be 17 surface modified to increase the wetting characteristics of the fibers, or may be treated to selectively remove and/or bind a particular molecule, cell, organism, or the like.

Surface characteristics of a fiber can be modified by a number of methods, for example, by chemical reaction including wet or dry oxidation, by coating the surface by Η depositing a polymer thereon, by grafting reactions which are activated by exposure to an energy source such as gas plasma, heat, a Van der Graff generator, ultraviolet light, or to various other forms of radiation, or by surface etching or deposition using a gas plasma treatment. 25 Appropriate lengths, diameters and rigidities may be specified for fibers 23 in order to achieve a desired result. Specification of attributes may depend on the nature of the material which is to be collected at collection site 21 or on manufacturing considerations. The shape of fibers 23 may also be selected in accordance with a desired 29 result such as the selective attraction or repulsion of chemicals or solid phase suspended within a liquid sample.

Individual fibers 23 may be selectively shaped to achieve a desired result. Shapes may include tapering of the fiber from base to tip, or increasing the diameter between the mounted end and the distal end. Fibers may have circular or rectilinear cross sections. Individual fibers may have hollow centers or laminated construction to permit the transport of solid or liquid phase therethrough or otherwise improve the collection result.

In accordance with the invention, fibers 23 or a surface thereof may be treated to achieve a desired result. This may be achieved by selecting materials or treating materials from which the fiber is to be made. Treatment may involve treating the surface or subsurface of the fiber following formation. Fibers may also be provided which are selectively permeable, non-permeable, or semi-permeable.

Fiber materials or fiber treatment may permit the fiber to selectively absorb and/or transport desired or undesired solid and/or fluid phase. Such treatment may also provide selective attraction or repulsion of suspended solid phase. In a preferred embodiment, fiber material is selected and/or fibers are treated to selectively capture a desired material. The fibers or the collection arrangement may also be transported, in or out of the housing, to a site other than the collection site for processing. Fibers 23 may be treated or formed from a material in order to chemically attract or repel selected materials. In other embodiments of the invention, treatment of the fiber 23 may be applied to specific areas such as the tip portion, base, or interstitial areas. Such treatment may be made to the material from which the fiber is formed, and/or to undersurface layers of a fiber.

Fiber surfaces may have features or structure incorporated thereon. Such features and/or structure may include, but are not limited to, pores, scoring, abrading, barbs, follicles, and/or protuberances. Surface structures on the fibers 23 can be adapted to selectively receive or repel solid phase within the liquid phase or increase the effective surface area of the fiber and/or the collection site 21.

Combinations of the various fiber treatments, constructions, and surface features also are contemplated as being within the scope of the invention. The substrate 24 on which the fibers 23 are mounted may be made from the same material as the fibers 23, or may be different. The substrate may also be formed of a permeable, non-permeable, or semi-permeable material. The substrate 24 may also be formed from a material having properties which selectively attract or repel specified material.

Substrate 24 may also be treated in order to achieve a desired result as noted above. Treatment of the substrate 24 may enhance the substrate's ability to attract or repel selected matter. For example, the substrate 24 and/or the fibers 23 may include agents or molecules which provide a positive indication of the presence of a predetermined solid, such as a color forming agent or the like which becomes visible if certain substance is present. The substrate may be formed in any of a number of shapes, including but not limited to, a disk, plane, concave/convex disk, or lattice structure. An exemplary embodiment is depicted in the Figures. A substrate may have flow through channels formed therein to enhance the passage of material therethrough. Optionally, the substrate or collection arrangement may include an optical channel that permits communication between a radiant energy source, such as an infra-red spectrometer, the collection site (or solid matter captured on the collection site), and an absorbance meter. The optical channel may be a channel, hole, or the like of any shape through the collection arrangement, e.g., a centrally positioned annular hole.

The fibers and/or strands may be attached or supported using any means, including but not limited to hot welding, adhesively binding, extrusion, integral formation with the substrate, or the like. Arrangement of fibers 23 on the substrate may be in an appropriate formation to achieve a desired result. Exemplary arrangements may place fibers on the substrate randomly, in rows, concentric rings, bunches, a spiral, and/or in any other suitable arrangement. Collection arrangement 20 may be positioned in any housing having an inlet 11 and allowing passage of a fluid through a collection site 21. The housing may also include an outlet 12, if desired. In some embodiments, an inlet and an outlet may be configured into or within a single port. Inlet 11 may be configured in any suitable manner for providing an inlet into separation device 10, and outlet 12 may be configured in any suitable manner for providing an outlet out of separation device 10. For example, inlet 11 and/or outlet 12 may be configured as a connector and may be adapted to connect to a container, a needle or cannula, or the like. Exemplary connector configurations include but are not limited to friction, tapered hose and threaded. Other exemplary configurations of the inlet 11 and/or outlet 12 include a threaded or non-threaded luer lock. Any housing of suitable shape to provide an inlet and an outlet may be employed. The housing may be fabricated from any suitably rigid, impervious material, including any impervious thermoplastic material, which is compatible with the fluid being processed. The housing may include an arrangement of one or more channels, grooves, conduits, passages, ribs, or the like, which may be serpentine, parallel, curved, circular, or a variety of other configurations.

The present invention, an exemplary embodiment of which is shown in Figure 2, may also include a separation shuttle 10, comprising first and second detachable portions 44, 42, having first and second ports 11, 12, respectively. The first and second detachable portions 44, 42 define a chamber 50 and the first and second ports 11, 12 define at least one fluid flow path through the chamber 50. The collection arrangement 20 within the separation apparatus 10 is preferably as described above. A preferred embodiment of the invention includes a separation device 10 comprising a shuttle which may be mounted on a specimen or collection cup 30 in which fluids, such as urine or other biological fluids, may be collected. The collection cup 30 may be any container suitable for collection of body fluids. After fluid collection, the patient or supervising medical personnel places a lid 31 on the cup housing 16. The cup housing 16 is preferably provided with an external threaded surface 100. The cover or lid 31 may include a vent hole 13a with an optional removable vent cap 13b. The vent hole 13a may also be used to introduce a brush or spatula into the cup containing physiological saline solution or preservative after brushing or scraping the body site to obtain the specimen. Preferably, the lid has a body 102 which is molded with a downwardly directed cylindrical extended skirt or flange 104 which is threaded 24 on its inner surface 23 for screwing onto the external threaded surface 100 of the cup housing 16. The lid body 102 also defines a well 26 in which a threaded port 32 may be integrally molded. The port 32 is provided with a channel 29 or the like leading to a hollow tube 33 which is preferably separately secured to the other side of the lid body in a circular planar seat 106 with its lumen or channel

29 being axially aligned with the port 32. The tube 33 may have a series of perforations 110 and an open end 110 near the bottom of the collection cup 30 which allow different fluid layers as well as sediments to be simultaneously tested when the fluid sample is withdrawn from the cup.

As shown in the figures the separation shuttle 10 is preferably a two piece housing with a first detachable portion 44 and a second detachable portion 42, although any housing providing access to the collection arrangement 20 is suitable. The collection arrangement 20 may be mounted on an annular step or seat 43 formed in the interior cavity 50 of the second detachable portion 42.

Any means suitable for inducing the flow of fluid from a source container through the separation shuttle apparatus may be used as part of the present invention. Exemplary fluid flow inducing means include, but are not limited to a syringe or pump type device. In place of syringe 34 any suitable pump type device, such as an autovial spunglass filter manufactured by Genex Corporation, could be used. Also included in the scope of the present invention is the use of a flexible, collapsible container, such as a specimen container, which may be squeezed to force fluid through the collection apparatus and into the container.

When the biological fluid is pulled from the collection cup 30 through tube 33 and port 11 of the first detachable portion 44, fluid flows through the collection arrangement 20 so that a solid phase, such as cells, is captured in the fibers 23.

The separation shuttle 10 may then be disconnected from collection cup 30 and, optionally, from syringe 34. It may then be unscrewed into two parts and the second detachable portion 42 and the collection arrangement and/or fibers may be placed on a microscope slide or other diagnostic element. This allows a examination to be performed on matter, such as cells, by the practitioner without interference or delay due to processing requirements.

A treatment device may also be used in combination with the separation shuttle 10. Any suitable diagnostic or detection assembly may be used in conjunction with the separation shuttle 10. However, a preferable device is an apparatus for testing for the presence of cancer utilizing a sandwich assay. For example, the apparatus may comprise a housing including inlet and outlet ports defining a flow path between the inlet and the outlet; a collection arrangement positioned across the flow path; and chromatography and/or assay elements positioned downstream of the collection arrangement, as disclosed in U.S. Patent No. 5,137,031. As used herein, fluid refers to any fluid for which it may be desirable to collect a component of the fluid for the purpose of establishing its identity or presence in the fluid. Typically, the component in the fluid will be a solid matter, such as particulate matter. For example, the fluid may be air or gas, or a biological fluid, such as urine, and it may be desirable to determine the presence of cancer cells or certain proteins in the biological fluid. In another example, it may be desirable to evaluate the nature of contaminants, such as molecular contaminants, in ultra-pure water used in the electronics industry. Other exemplary fluids include but are not limited to other body fluids, such as blood, spinal fluid, or amniotic fluid; bronchial lavage; sputum; fine needle aspirates; ground water; industrial processing fluids; electronic or medical dialysis fluids; to identify just a few. It is intended that the invention should not be limited by the type of fluid being processed. A desired collection result may involve not only the attraction, capture or collection of a suspended solid phase within the collection site, but also the designated repulsion of specified material from the collection site.

In accordance with the invention, any solid in a fluid suspension may be removed from the fluid as the suspension is processed through a solid-liquid separation apparatus of the invention. As used herein, solid matter refers to any substance in a fluid which is capable of collection and evaluation using radiant energy sources. Exemplary matter includes, but is not limited to cells or cell fragments, proteins, molecules, polymers, rubbers, stabilizers, antioxidants, accelerators, silicones, alkyds, thiokols, paraffins, thermoplastics, bacteria, pesticides, and herbicides. Specific exemplary polymeric matter include, but is not limited to polyethylene, polypropylene, polyisobutylene, polyacrylonitrile, polyethylene glycol, polyvinylchloride, polystyrene, polysulfide, polymethylmethacrylates, polyethyleneterephthalates, bisphenol A (a common environmental contaminant), ethyl cellulose, nitrocellulose, polyurethane, and nylon. Specific exemplary biological matter includes cancer cells, including distinguishing between metastatic and normal cancer cells; proteins, nucleic acids, antibodies, or the like. It is intended that the invention should not be limited by the type of matter being processed. The solid-liquid separation apparatus of the present invention also allows for isolation and collection of fresh cells and/or microorganisms from biological fluids to perform DNA probe and chromosomal analysis once the cells are hemolyzed by the proper buffer.

It is intended the invention is not to be limited by the type of solid being removed or captured from the fluid suspension. In another embodiment, the separation apparatus and/or assembly may be included in a kit. The kit may include additional components, such as but not limited to slides and/or petri dishes and the like; and reagents such as fixatives, preservatives, and stains and the like. > A solid-liquid separation kit may also include a means for inducing fluid flow through the collection and distribution apparatus, preferably a syringe, removably mounted to the collection apparatus.

METHOD OF SEPARATING A SOLID FROM LIQUID

The present invention includes a method for directing a liquid sample into contact with a collection arrangement as described above. In accordance with the method, material in the sample may be received at the collection arrangement 20 or may pass depending on the selected design attributes of the collection arrangement.

Passing of the sample across the collection arrangement 20 may involve establishing a pressure differential across collection arrangement 20 to cause the sample to pass through the separation apparatus 10 under conditions in which solid phase is collected in or deposited on the collection site 21 and the liquid phase passes through or by the collection arrangement 20. Preferably, selected solid phase is releasibly collected in the collection site 21. It should be appreciated that the inventive method is not limited to capturing solid phase within the collection arrangement. Selective collection or repulsion of any material using the collection arrangement is contemplated within the scope of the invention.

In a preferred embodiment, a portion of the collection arrangement captures the solid phase, and, optionally, the capturing portion may be separated from the separation device for additional processing.

As shown in Figure 3, passing a fluid sample across the collection arrangement 20 causes the solid phase suspended in the liquid phase to pass into collection site 21. As a result, solid phase collects in, or is deposited on the fibers or fiber-like elements 23 in collection site 21. In an optional embodiment of the invention, as more and more solid phase is collected in the fibers or fiber-like elements, fluid flow increases near the edges of the collection arrangement, and fluid may pass through channels 22 and into a downstream section of the housing.

Processing a solid-liquid suspension in accordance with the invention may also include passing other material through the separation apparatus 10. For example, one or more fluids may be passed through the collection arrangement 20, before and/or after the passage of the solid-liquid suspension through the separation apparatus. In one embodiment, a thin layer of solids may be deposited on the collection site of solid-liquid separation apparatus as described above followed by passing a solution containing a fixative, such as alcohol or acetone, through the apparatus. In a preferred embodiment of the invention, following collection of material in the collection site, the housing of the solid-liquid separation apparatus can be opened to allow access to the collection arrangement, preferably to the collection site. This permits immediate access to the collection site for immediate processing, e.g., immediately determining the presence of a solid, or, to provide for the transfer of the collected solids or materials from the collection site to another apparatus or device for additional processing.

For example, the collection site may be placed in contact with a device, such as an analytical, diagnostic or culturing device, to transfer the collected solids to the device.

In a more preferred embodiment, the collection site may be placed in contact with the device in a fashion which permits the solids to form a smear or a thin layer, and in some cases, a monolayer, on the device. Any device suitable for the transfer of the solids may be used as part of the instant invention for processing the solid material. The device and/or process utilized may depend on the intended use of the solid material, as is known to one of skill in the art. For example, the solid material may be transferred to one or more microscope slides, porous media, and petri dishes. Processing the solid material may include treatment, e.g., filtration, isolation, analysis, diagnosis, and/or culturing.

The invention also involves a method for automatically processing a biological fluid comprising passing a biological fluid from a source container to a collection arrangement comprising using an automatic control device to pass the biological fluid through the collection arrangement under conditions in which a solid element in the fluid is removed and/or concentrated from the fluid. Automatic processing may also include mechanical means for exposing the collection arrangement for additional processing of the captured particulate matter (i.e., cytological examination), or for passing the "treated" fluid into another chamber or container for additional processing (e.g., assay or chromatography processes). Processing the collected solid material includes virtually all forms of detection and diagnostic procedures, and may be selected according to the type of solid(s) matter removed from the liquid. For example, if cancer cells are being removed from urine, it may be desirable to subject the captured cells to, cytological studies. Processing may include depositing the solid material on at least one medium and petri dish, e.g., for isolating and/or culturing captured solid material such microorganisms, particularly bacteria. In one embodiment, processing may also include lysing solid material such as cells, more preferably, processing may include lysing followed by nucleic acid analysis, e.g., hybridization.

Although the present invention has been described in terms of a particular preferred embodiments, it is not limited to those embodiments. Alternative embodiments, examples, and modifications which would still be encompassed by the invention may be made by those skilled in the art, particularly in light of the foregoing teachings. Therefore, the following claims are intended to cover any alternative embodiments, examples, modifications, or equivalents which may be included within the spirit and scope of the invention as defined by the claims.

Claims

Claims:
1. A method for processing a fluid comprising: directing a fluid through a substrate having plurality of selectively receptive fibers; and collecting matter suspended within the fluid with the selectively receptive fibers.
2. The method of claim 1 wherein collecting matter suspended within the fluid includes collecting a solid phase.
3. The method of claim 1 wherein collecting matter suspended within the fluid includes concentrating the collected matter.
4. The method of claim 2 further comprises determining the presence of the solid phase.
5. The method of claim 4 wherein determining the presence of the solid phase includes determining the presence of a specific analyte.
6. The method of claim 4 wherein determining the presence of the solid phase includes determining the presence of multiple analytes.
7. The method of claim 1 further comprising transporting the substrate and fibers to a laboratory for further testing.
8. The method of claim 1 wherein collecting matter suspended within the fluid includes determining the presence of at least one analyte in the fluid while the fluid is being processed.
9. A separation apparatus comprising: a housing having an inlet and defining at least one fluid flow path through the housing; and a collection arrangement disposed in the housing across the fluid flow path, said collection arrangement including a plurality of selectively receptive fibers for capturing a solid in a liquid suspension, said fibers having a supported end and a non-supported end.
10. The separation apparatus of claim 9 wherein the selectively receptive fibers are suitable for determining the presence of the solid phase.
11. The separation apparatus of claim 10 wherein the fibers include a chromatography substrate suitable for determining the presence of multiple different analytes.
12. The separation apparatus of claim 10 wherein the fibers include an assay substrate suitable for determining the presence of a specific analyte.
13. The separation apparatus of claim 9 wherein the collection arrangement includes at least one channel for passing liquid through the collection arrangement.
14. The separation apparatus of claim 9 wherein the collection arrangement is transportable.
15. The separation apparatus of claim 9 wherein the inlet is suitable for attachment to a fluid source container.
16. The separation apparatus of claim 9 further comprising a debris filter in fluid communication with the collection arrangement.
17. The separation apparatus of claim 10 wherein the fibers are non-porous.
18. A solid-liquid separation assembly comprising: a housing having an inlet and an outlet and defining at least one fluid flow path between the inlet and the outlet; a collection arrangement disposed in the housing across the fluid flow path, said collection arrangement including a collection site for capturing a solid in a liquid suspension, wherein said collection site includes a fiber-like element having a supported end and a non-supported end; a container in fluid communication with the inlet; and a container in fluid communication with the outlet.
19. A fluid processing kit comprising: a housing having an inlet and an outlet and defining at least one fluid flow path between the inlet and the outlet; a collection arrangement disposed in the housing across the fluid flow path, said collection arrangement including a collection site for capturing a solid in a liquid suspension and at least one channel for passing liquid through the collection arrangement, wherein said collection site includes a fiber-like element having a supported end and a non-supported end; and at least one of a container adapted for fluid communication with the inlet; a container adapted for fluid communication with the outlet; and at least one reagent for enhancing the presentation of the captured solid.
PCT/US1996/010018 1995-06-07 1996-06-07 Method and apparatus for solid-liquid separation WO1996040408A1 (en)

Priority Applications (2)

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US47610595 true 1995-06-07 1995-06-07
US08/476,105 1995-06-07

Applications Claiming Priority (1)

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AU6272196A AU6272196A (en) 1995-06-07 1996-06-07 Method and apparatus for solid-liquid separation

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WO1996040408A1 true true WO1996040408A1 (en) 1996-12-19

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US4554073A (en) * 1983-03-21 1985-11-19 Rhodia Aktiengesellschaft Device for uptake, transportation, and recovery of cell material, and for transfer of the recovered material to microscope slides
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US4765895A (en) * 1982-12-27 1988-08-23 Sarstedt Apparatus for recovery of cell material from body fluids
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